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Jean-claude Mamputu - One of the best experts on this subject based on the ideXlab platform.

  • The Growth Hormone Releasing Hormone Analogue, Tesamorelin, Decreases Muscle Fat and Increases Muscle Area in Adults with HIV.
    The Journal of frailty & aging, 2019
    Co-Authors: S. Adrian, Jordan E Lake, Ann Scherzinger, Michael P Dube, Takara L Stanley, Steven K Grinspoon, Julian Falutz, Jean-claude Mamputu, A. Sanyal, C. Marsolais
    Abstract:

    Tesamorelin, a growth hormone-releasing hormone analogue, decreases visceral adipose tissue in people living with HIV, however, the effects on skeletal muscle fat and area are unknown. The goals of this exploratory secondary analysis were to determine the effects of Tesamorelin on muscle quality (density) and quantity (area). Secondary, exploratory analysis of two previously completed randomized (2:1), clinical trials. U.S. and Canadian sites. People living with HIV and with abdominal obesity. Tesamorelin participants were restricted to responders (visceral adipose tissue decrease ≥8%). Tesamorelin or placebo. Computed tomography scans (at L4-L5) were used to quantify total and lean density (Hounsfield Units, HU) and area (centimeters2) of four trunk muscle groups using a semi-automatic segmentation image analysis program. Differences between muscle area and density before and after 26 weeks of Tesamorelin or placebo treatment were compared and linear regression models were adjusted for baseline and treatment arm. Tesamorelin responders (n=193) and placebo (n=148) participants with available images were similar at baseline; most were Caucasian (83%) and male (87%). In models adjusted for baseline differences and treatment arm, Tesamorelin was associated with significantly greater increases in density of four truncal muscle groups (coefficient 1.56-4.86 Hounsfield units; all p

  • the growth hormone releasing hormone analogue Tesamorelin decreases muscle fat and increases muscle area in adults with hiv
    The Journal of frailty & aging, 2018
    Co-Authors: S. Adrian, Jordan E Lake, Ann Scherzinger, Michael P Dube, Takara L Stanley, Steven K Grinspoon, Julian Falutz, Jean-claude Mamputu, A. Sanyal, C. Marsolais
    Abstract:

    Tesamorelin, a growth hormone-releasing hormone analogue, decreases visceral adipose tissue in people living with HIV, however, the effects on skeletal muscle fat and area are unknown. The goals of this exploratory secondary analysis were to determine the effects of Tesamorelin on muscle quality (density) and quantity (area). Secondary, exploratory analysis of two previously completed randomized (2:1), clinical trials. U.S. and Canadian sites. People living with HIV and with abdominal obesity. Tesamorelin participants were restricted to responders (visceral adipose tissue decrease ≥8%). Tesamorelin or placebo. Computed tomography scans (at L4-L5) were used to quantify total and lean density (Hounsfield Units, HU) and area (centimeters2) of four trunk muscle groups using a semi-automatic segmentation image analysis program. Differences between muscle area and density before and after 26 weeks of Tesamorelin or placebo treatment were compared and linear regression models were adjusted for baseline and treatment arm. Tesamorelin responders (n=193) and placebo (n=148) participants with available images were similar at baseline; most were Caucasian (83%) and male (87%). In models adjusted for baseline differences and treatment arm, Tesamorelin was associated with significantly greater increases in density of four truncal muscle groups (coefficient 1.56-4.86 Hounsfield units; all p<0.005), and the lean anterolateral/abdominal and rectus muscles (1.39 and 1.78 Hounsfield units; both p<0.005) compared to placebo. Significant increases were also seen in total area of the rectus and psoas muscles (0.44 and 0.46 centimeters2; p<0.005), and in the lean muscle area of all four truncal muscle groups (0.64-1.08 centimeters2; p<0.005). Among those with clinically significant decrease in visceral adipose tissue on treatment, Tesamorelin was effective in increasing skeletal muscle area and density. Long term effectiveness of Tesamorelin among people with and without HIV, and the impact of these changes in daily life should be further studied.

  • Visceral fat reduction with Tesamorelin is associated with improved liver enzymes in HIV.
    AIDS (London England), 2017
    Co-Authors: Lindsay T. Fourman, Takara L Stanley, Julian Falutz, Jean-claude Mamputu, Meghan N. Feldpausch, C. Marsolais, Josée Morin, Natalia Czerwonka, Julian J Weiss, Steven K Grinspoon
    Abstract:

    OBJECTIVE Tesamorelin reduces visceral adipose tissue (VAT) in HIV. We investigated whether reductions in VAT with Tesamorelin are associated with changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST). DESIGN AND METHODS We utilized data from two multicenter Phase III trials of Tesamorelin among 806 HIV-infected patients with abdominal obesity. These studies showed that the majority of patients treated with Tesamorelin are 'responders', defined a priori by the Food and Drug Administration as achieving at least 8% reduction in VAT. In the current analysis, we sought to examine the impact of VAT reduction on ALT and AST among patients participating in the Phase III trials with baseline elevated ALT or AST. Within this group, we compared changes in ALT and AST in VAT responders vs. nonresponders after 26 weeks of treatment, and then assessed the effects of drug discontinuation on these endpoints over a subsequent 26-week period. RESULTS At baseline, VAT was positively associated with ALT (P = 0.01). In study participants assigned to Tesamorelin with baseline ALT or AST more than 30 U/l, VAT responders experienced greater reductions in ALT (-8.9 ± 22.6 vs. 1.4 ± 34.7 U/l, P = 0.004) and AST (-3.8 ± 12.9 vs. 0.4 ± 22.4 U/l, P = 0.04) compared with nonresponders over 26 weeks. This improvement among VAT responders persisted over 52 weeks even in those switched to placebo despite a partial reaccumulation of VAT. CONCLUSION A clinically significant VAT reduction with Tesamorelin was associated with improved liver enzymes among HIV-infected patients with abdominal obesity and elevated baseline transaminases.

  • safety and metabolic effects of Tesamorelin a growth hormone releasing factor analogue in patients with type 2 diabetes a randomized placebo controlled trial
    PLOS ONE, 2017
    Co-Authors: David R Clemmons, Samuel I Miller, Jean-claude Mamputu
    Abstract:

    Objective Use of growth hormone is associated with side effects, including insulin resistance. The objective of this study was to determine whether Tesamorelin, a stabilized growth hormone-releasing hormone analogue, would alter insulin sensitivity or control of diabetes. Design A 12-week randomized, placebo-controlled study of 53 patients with type 2 diabetes. Three treatment groups: placebo, 1 and 2 mg Tesamorelin. Measurements Fasting glucose, glucose and insulin from oral glucose tolerance test, glycosylated hemoglobin (HbA1c), home blood glucose, insulin-like growth factor-1, and lipids. Main outcome measure Relative insulin response following oral ingestion of glucose. Results No significant differences were observed between groups in relative insulin response over the 12-week treatment period. At Week 12, fasting glucose, HbA1c and overall diabetes control were not significantly different between groups. In addition, relevant modifications in diabetes medications were similar between groups. Total cholesterol (-0.3±0.6 mmol/L) and non-HDL cholesterol (-0.3±0.5 mmol/L) significantly decreased from baseline to Week 12 in the Tesamorelin 2 mg group (p<0.05 vs. placebo). No patient discontinued the study due to loss of diabetes control. Conclusions Treatment of type 2 diabetic patients with Tesamorelin for 12 weeks did not alter insulin response or glycemic control. Trial registration ClinicalTrials.gov NCT01264497.

  • Safety and metabolic effects of Tesamorelin, a growth hormone-releasing factor analogue, in patients with type 2 diabetes: A randomized, placebo-controlled trial
    2017
    Co-Authors: David R Clemmons, Sam Miller, Jean-claude Mamputu
    Abstract:

    ObjectiveUse of growth hormone is associated with side effects, including insulin resistance. The objective of this study was to determine whether Tesamorelin, a stabilized growth hormone-releasing hormone analogue, would alter insulin sensitivity or control of diabetes.DesignA 12-week randomized, placebo-controlled study of 53 patients with type 2 diabetes. Three treatment groups: placebo, 1 and 2 mg Tesamorelin.MeasurementsFasting glucose, glucose and insulin from oral glucose tolerance test, glycosylated hemoglobin (HbA1c), home blood glucose, insulin-like growth factor-1, and lipids.Main outcome measureRelative insulin response following oral ingestion of glucose.ResultsNo significant differences were observed between groups in relative insulin response over the 12-week treatment period. At Week 12, fasting glucose, HbA1c and overall diabetes control were not significantly different between groups. In addition, relevant modifications in diabetes medications were similar between groups. Total cholesterol (-0.3±0.6 mmol/L) and non-HDL cholesterol (-0.3±0.5 mmol/L) significantly decreased from baseline to Week 12 in the Tesamorelin 2 mg group (p

Steven K Grinspoon - One of the best experts on this subject based on the ideXlab platform.

  • Tesamorelin improves fat quality independent of changes in fat quantity
    AIDS, 2021
    Co-Authors: Jordan E Lake, L A Kristen, Kristine M Erlandson, Stefan Adrian, Gayane Yenokyan, Ann Scherzinger, Michael P Dube, Takara L Stanley, Steven K Grinspoon, Julian Falutz
    Abstract:

    OBJECTIVES : Fat quality and quantity may affect health similarly or differently. Fat quality can be assessed by measuring fat density on CT scan (greater density=smaller, higher quality adipocytes). We assessed the effects of Tesamorelin, a growth hormone-releasing hormone analogue that reduces visceral fat (VAT) quantity in some people living with HIV (PLWH), on fat density. DESIGN : Participants from two completed, placebo-controlled, randomized trials of Tesamorelin for central adiposity treatment in PLWH were included if they had either a clinical response to Tesamorelin (VAT decrease ≥8%, ≈70% of participants) or were placebo-treated. METHODS : CT VAT and subcutaneous fat (SAT) density (Hounsfield Units, HU) were measured by a central blinded reader.Results: Participants (193 responders, 148 placebo) were 87% male and 83% Caucasian. Baseline characteristics were similar across arms, including VAT (-91 HU both arms, p = 0.80) and SAT density (-94 HU Tesamorelin, -95 HU placebo, p = 0.29). Over 26 weeks, mean (SD) VAT and SAT density increased in Tesamorelin-treated participants only (VAT: + 6.2 (8.7) HU Tesamorelin, + 0.3 (4.2) HU placebo, p < 0.0001; SAT: + 4.0 (8.7) HU Tesamorelin, + 0.3 (4.8) HU placebo, p < 0.0001). The Tesamorelin effects persisted after controlling for baseline VAT or SAT HU and area, and VAT (+2.3 HU, 95% CI [4.5, 7.3], p = 0.001) or SAT (+3.5 HU, 95% CI [2.3, 4.7], p < 0.001) area change. CONCLUSIONS : In PLWH with central adiposity who experienced VAT quantity reductions on Tesamorelin, VAT and SAT density increased independent of changes in fat quantity, suggesting that Tesamorelin also improves VAT and SAT quality in this group.

  • Tesamorelin Improves Fat Quality Independent of Changes in Fat Quantity.
    AIDS (London England), 2021
    Co-Authors: Jordan E Lake, Kristine M Erlandson, Stefan Adrian, Gayane Yenokyan, Ann Scherzinger, Michael P Dube, Takara L Stanley, Steven K Grinspoon, Julian Falutz
    Abstract:

    OBJECTIVES : Fat quality and quantity may affect health similarly or differently. Fat quality can be assessed by measuring fat density on CT scan (greater density=smaller, higher quality adipocytes). We assessed the effects of Tesamorelin, a growth hormone-releasing hormone analogue that reduces visceral fat (VAT) quantity in some people living with HIV (PLWH), on fat density. DESIGN : Participants from two completed, placebo-controlled, randomized trials of Tesamorelin for central adiposity treatment in PLWH were included if they had either a clinical response to Tesamorelin (VAT decrease ≥8%, ≈70% of participants) or were placebo-treated. METHODS : CT VAT and subcutaneous fat (SAT) density (Hounsfield Units, HU) were measured by a central blinded reader.Results: Participants (193 responders, 148 placebo) were 87% male and 83% Caucasian. Baseline characteristics were similar across arms, including VAT (-91 HU both arms, p = 0.80) and SAT density (-94 HU Tesamorelin, -95 HU placebo, p = 0.29). Over 26 weeks, mean (SD) VAT and SAT density increased in Tesamorelin-treated participants only (VAT: + 6.2 (8.7) HU Tesamorelin, + 0.3 (4.2) HU placebo, p 

  • The Growth Hormone Releasing Hormone Analogue, Tesamorelin, Decreases Muscle Fat and Increases Muscle Area in Adults with HIV.
    The Journal of frailty & aging, 2019
    Co-Authors: S. Adrian, Jordan E Lake, Ann Scherzinger, Michael P Dube, Takara L Stanley, Steven K Grinspoon, Julian Falutz, Jean-claude Mamputu, A. Sanyal, C. Marsolais
    Abstract:

    Tesamorelin, a growth hormone-releasing hormone analogue, decreases visceral adipose tissue in people living with HIV, however, the effects on skeletal muscle fat and area are unknown. The goals of this exploratory secondary analysis were to determine the effects of Tesamorelin on muscle quality (density) and quantity (area). Secondary, exploratory analysis of two previously completed randomized (2:1), clinical trials. U.S. and Canadian sites. People living with HIV and with abdominal obesity. Tesamorelin participants were restricted to responders (visceral adipose tissue decrease ≥8%). Tesamorelin or placebo. Computed tomography scans (at L4-L5) were used to quantify total and lean density (Hounsfield Units, HU) and area (centimeters2) of four trunk muscle groups using a semi-automatic segmentation image analysis program. Differences between muscle area and density before and after 26 weeks of Tesamorelin or placebo treatment were compared and linear regression models were adjusted for baseline and treatment arm. Tesamorelin responders (n=193) and placebo (n=148) participants with available images were similar at baseline; most were Caucasian (83%) and male (87%). In models adjusted for baseline differences and treatment arm, Tesamorelin was associated with significantly greater increases in density of four truncal muscle groups (coefficient 1.56-4.86 Hounsfield units; all p

  • the growth hormone releasing hormone analogue Tesamorelin decreases muscle fat and increases muscle area in adults with hiv
    The Journal of frailty & aging, 2018
    Co-Authors: S. Adrian, Jordan E Lake, Ann Scherzinger, Michael P Dube, Takara L Stanley, Steven K Grinspoon, Julian Falutz, Jean-claude Mamputu, A. Sanyal, C. Marsolais
    Abstract:

    Tesamorelin, a growth hormone-releasing hormone analogue, decreases visceral adipose tissue in people living with HIV, however, the effects on skeletal muscle fat and area are unknown. The goals of this exploratory secondary analysis were to determine the effects of Tesamorelin on muscle quality (density) and quantity (area). Secondary, exploratory analysis of two previously completed randomized (2:1), clinical trials. U.S. and Canadian sites. People living with HIV and with abdominal obesity. Tesamorelin participants were restricted to responders (visceral adipose tissue decrease ≥8%). Tesamorelin or placebo. Computed tomography scans (at L4-L5) were used to quantify total and lean density (Hounsfield Units, HU) and area (centimeters2) of four trunk muscle groups using a semi-automatic segmentation image analysis program. Differences between muscle area and density before and after 26 weeks of Tesamorelin or placebo treatment were compared and linear regression models were adjusted for baseline and treatment arm. Tesamorelin responders (n=193) and placebo (n=148) participants with available images were similar at baseline; most were Caucasian (83%) and male (87%). In models adjusted for baseline differences and treatment arm, Tesamorelin was associated with significantly greater increases in density of four truncal muscle groups (coefficient 1.56-4.86 Hounsfield units; all p<0.005), and the lean anterolateral/abdominal and rectus muscles (1.39 and 1.78 Hounsfield units; both p<0.005) compared to placebo. Significant increases were also seen in total area of the rectus and psoas muscles (0.44 and 0.46 centimeters2; p<0.005), and in the lean muscle area of all four truncal muscle groups (0.64-1.08 centimeters2; p<0.005). Among those with clinically significant decrease in visceral adipose tissue on treatment, Tesamorelin was effective in increasing skeletal muscle area and density. Long term effectiveness of Tesamorelin among people with and without HIV, and the impact of these changes in daily life should be further studied.

  • Visceral fat reduction with Tesamorelin is associated with improved liver enzymes in HIV.
    AIDS (London England), 2017
    Co-Authors: Lindsay T. Fourman, Takara L Stanley, Julian Falutz, Jean-claude Mamputu, Meghan N. Feldpausch, C. Marsolais, Josée Morin, Natalia Czerwonka, Julian J Weiss, Steven K Grinspoon
    Abstract:

    OBJECTIVE Tesamorelin reduces visceral adipose tissue (VAT) in HIV. We investigated whether reductions in VAT with Tesamorelin are associated with changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST). DESIGN AND METHODS We utilized data from two multicenter Phase III trials of Tesamorelin among 806 HIV-infected patients with abdominal obesity. These studies showed that the majority of patients treated with Tesamorelin are 'responders', defined a priori by the Food and Drug Administration as achieving at least 8% reduction in VAT. In the current analysis, we sought to examine the impact of VAT reduction on ALT and AST among patients participating in the Phase III trials with baseline elevated ALT or AST. Within this group, we compared changes in ALT and AST in VAT responders vs. nonresponders after 26 weeks of treatment, and then assessed the effects of drug discontinuation on these endpoints over a subsequent 26-week period. RESULTS At baseline, VAT was positively associated with ALT (P = 0.01). In study participants assigned to Tesamorelin with baseline ALT or AST more than 30 U/l, VAT responders experienced greater reductions in ALT (-8.9 ± 22.6 vs. 1.4 ± 34.7 U/l, P = 0.004) and AST (-3.8 ± 12.9 vs. 0.4 ± 22.4 U/l, P = 0.04) compared with nonresponders over 26 weeks. This improvement among VAT responders persisted over 52 weeks even in those switched to placebo despite a partial reaccumulation of VAT. CONCLUSION A clinically significant VAT reduction with Tesamorelin was associated with improved liver enzymes among HIV-infected patients with abdominal obesity and elevated baseline transaminases.

Julian Falutz - One of the best experts on this subject based on the ideXlab platform.

  • Tesamorelin improves fat quality independent of changes in fat quantity
    AIDS, 2021
    Co-Authors: Jordan E Lake, L A Kristen, Kristine M Erlandson, Stefan Adrian, Gayane Yenokyan, Ann Scherzinger, Michael P Dube, Takara L Stanley, Steven K Grinspoon, Julian Falutz
    Abstract:

    OBJECTIVES : Fat quality and quantity may affect health similarly or differently. Fat quality can be assessed by measuring fat density on CT scan (greater density=smaller, higher quality adipocytes). We assessed the effects of Tesamorelin, a growth hormone-releasing hormone analogue that reduces visceral fat (VAT) quantity in some people living with HIV (PLWH), on fat density. DESIGN : Participants from two completed, placebo-controlled, randomized trials of Tesamorelin for central adiposity treatment in PLWH were included if they had either a clinical response to Tesamorelin (VAT decrease ≥8%, ≈70% of participants) or were placebo-treated. METHODS : CT VAT and subcutaneous fat (SAT) density (Hounsfield Units, HU) were measured by a central blinded reader.Results: Participants (193 responders, 148 placebo) were 87% male and 83% Caucasian. Baseline characteristics were similar across arms, including VAT (-91 HU both arms, p = 0.80) and SAT density (-94 HU Tesamorelin, -95 HU placebo, p = 0.29). Over 26 weeks, mean (SD) VAT and SAT density increased in Tesamorelin-treated participants only (VAT: + 6.2 (8.7) HU Tesamorelin, + 0.3 (4.2) HU placebo, p < 0.0001; SAT: + 4.0 (8.7) HU Tesamorelin, + 0.3 (4.8) HU placebo, p < 0.0001). The Tesamorelin effects persisted after controlling for baseline VAT or SAT HU and area, and VAT (+2.3 HU, 95% CI [4.5, 7.3], p = 0.001) or SAT (+3.5 HU, 95% CI [2.3, 4.7], p < 0.001) area change. CONCLUSIONS : In PLWH with central adiposity who experienced VAT quantity reductions on Tesamorelin, VAT and SAT density increased independent of changes in fat quantity, suggesting that Tesamorelin also improves VAT and SAT quality in this group.

  • Tesamorelin Improves Fat Quality Independent of Changes in Fat Quantity.
    AIDS (London England), 2021
    Co-Authors: Jordan E Lake, Kristine M Erlandson, Stefan Adrian, Gayane Yenokyan, Ann Scherzinger, Michael P Dube, Takara L Stanley, Steven K Grinspoon, Julian Falutz
    Abstract:

    OBJECTIVES : Fat quality and quantity may affect health similarly or differently. Fat quality can be assessed by measuring fat density on CT scan (greater density=smaller, higher quality adipocytes). We assessed the effects of Tesamorelin, a growth hormone-releasing hormone analogue that reduces visceral fat (VAT) quantity in some people living with HIV (PLWH), on fat density. DESIGN : Participants from two completed, placebo-controlled, randomized trials of Tesamorelin for central adiposity treatment in PLWH were included if they had either a clinical response to Tesamorelin (VAT decrease ≥8%, ≈70% of participants) or were placebo-treated. METHODS : CT VAT and subcutaneous fat (SAT) density (Hounsfield Units, HU) were measured by a central blinded reader.Results: Participants (193 responders, 148 placebo) were 87% male and 83% Caucasian. Baseline characteristics were similar across arms, including VAT (-91 HU both arms, p = 0.80) and SAT density (-94 HU Tesamorelin, -95 HU placebo, p = 0.29). Over 26 weeks, mean (SD) VAT and SAT density increased in Tesamorelin-treated participants only (VAT: + 6.2 (8.7) HU Tesamorelin, + 0.3 (4.2) HU placebo, p 

  • The Growth Hormone Releasing Hormone Analogue, Tesamorelin, Decreases Muscle Fat and Increases Muscle Area in Adults with HIV.
    The Journal of frailty & aging, 2019
    Co-Authors: S. Adrian, Jordan E Lake, Ann Scherzinger, Michael P Dube, Takara L Stanley, Steven K Grinspoon, Julian Falutz, Jean-claude Mamputu, A. Sanyal, C. Marsolais
    Abstract:

    Tesamorelin, a growth hormone-releasing hormone analogue, decreases visceral adipose tissue in people living with HIV, however, the effects on skeletal muscle fat and area are unknown. The goals of this exploratory secondary analysis were to determine the effects of Tesamorelin on muscle quality (density) and quantity (area). Secondary, exploratory analysis of two previously completed randomized (2:1), clinical trials. U.S. and Canadian sites. People living with HIV and with abdominal obesity. Tesamorelin participants were restricted to responders (visceral adipose tissue decrease ≥8%). Tesamorelin or placebo. Computed tomography scans (at L4-L5) were used to quantify total and lean density (Hounsfield Units, HU) and area (centimeters2) of four trunk muscle groups using a semi-automatic segmentation image analysis program. Differences between muscle area and density before and after 26 weeks of Tesamorelin or placebo treatment were compared and linear regression models were adjusted for baseline and treatment arm. Tesamorelin responders (n=193) and placebo (n=148) participants with available images were similar at baseline; most were Caucasian (83%) and male (87%). In models adjusted for baseline differences and treatment arm, Tesamorelin was associated with significantly greater increases in density of four truncal muscle groups (coefficient 1.56-4.86 Hounsfield units; all p

  • the growth hormone releasing hormone analogue Tesamorelin decreases muscle fat and increases muscle area in adults with hiv
    The Journal of frailty & aging, 2018
    Co-Authors: S. Adrian, Jordan E Lake, Ann Scherzinger, Michael P Dube, Takara L Stanley, Steven K Grinspoon, Julian Falutz, Jean-claude Mamputu, A. Sanyal, C. Marsolais
    Abstract:

    Tesamorelin, a growth hormone-releasing hormone analogue, decreases visceral adipose tissue in people living with HIV, however, the effects on skeletal muscle fat and area are unknown. The goals of this exploratory secondary analysis were to determine the effects of Tesamorelin on muscle quality (density) and quantity (area). Secondary, exploratory analysis of two previously completed randomized (2:1), clinical trials. U.S. and Canadian sites. People living with HIV and with abdominal obesity. Tesamorelin participants were restricted to responders (visceral adipose tissue decrease ≥8%). Tesamorelin or placebo. Computed tomography scans (at L4-L5) were used to quantify total and lean density (Hounsfield Units, HU) and area (centimeters2) of four trunk muscle groups using a semi-automatic segmentation image analysis program. Differences between muscle area and density before and after 26 weeks of Tesamorelin or placebo treatment were compared and linear regression models were adjusted for baseline and treatment arm. Tesamorelin responders (n=193) and placebo (n=148) participants with available images were similar at baseline; most were Caucasian (83%) and male (87%). In models adjusted for baseline differences and treatment arm, Tesamorelin was associated with significantly greater increases in density of four truncal muscle groups (coefficient 1.56-4.86 Hounsfield units; all p<0.005), and the lean anterolateral/abdominal and rectus muscles (1.39 and 1.78 Hounsfield units; both p<0.005) compared to placebo. Significant increases were also seen in total area of the rectus and psoas muscles (0.44 and 0.46 centimeters2; p<0.005), and in the lean muscle area of all four truncal muscle groups (0.64-1.08 centimeters2; p<0.005). Among those with clinically significant decrease in visceral adipose tissue on treatment, Tesamorelin was effective in increasing skeletal muscle area and density. Long term effectiveness of Tesamorelin among people with and without HIV, and the impact of these changes in daily life should be further studied.

  • Visceral fat reduction with Tesamorelin is associated with improved liver enzymes in HIV.
    AIDS (London England), 2017
    Co-Authors: Lindsay T. Fourman, Takara L Stanley, Julian Falutz, Jean-claude Mamputu, Meghan N. Feldpausch, C. Marsolais, Josée Morin, Natalia Czerwonka, Julian J Weiss, Steven K Grinspoon
    Abstract:

    OBJECTIVE Tesamorelin reduces visceral adipose tissue (VAT) in HIV. We investigated whether reductions in VAT with Tesamorelin are associated with changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST). DESIGN AND METHODS We utilized data from two multicenter Phase III trials of Tesamorelin among 806 HIV-infected patients with abdominal obesity. These studies showed that the majority of patients treated with Tesamorelin are 'responders', defined a priori by the Food and Drug Administration as achieving at least 8% reduction in VAT. In the current analysis, we sought to examine the impact of VAT reduction on ALT and AST among patients participating in the Phase III trials with baseline elevated ALT or AST. Within this group, we compared changes in ALT and AST in VAT responders vs. nonresponders after 26 weeks of treatment, and then assessed the effects of drug discontinuation on these endpoints over a subsequent 26-week period. RESULTS At baseline, VAT was positively associated with ALT (P = 0.01). In study participants assigned to Tesamorelin with baseline ALT or AST more than 30 U/l, VAT responders experienced greater reductions in ALT (-8.9 ± 22.6 vs. 1.4 ± 34.7 U/l, P = 0.004) and AST (-3.8 ± 12.9 vs. 0.4 ± 22.4 U/l, P = 0.04) compared with nonresponders over 26 weeks. This improvement among VAT responders persisted over 52 weeks even in those switched to placebo despite a partial reaccumulation of VAT. CONCLUSION A clinically significant VAT reduction with Tesamorelin was associated with improved liver enzymes among HIV-infected patients with abdominal obesity and elevated baseline transaminases.

Takara L Stanley - One of the best experts on this subject based on the ideXlab platform.

  • Delineating Tesamorelin response pathways in HIV-associated NAFLD using a targeted proteomic and transcriptomic approach
    Scientific Reports, 2021
    Co-Authors: Lindsay T. Fourman, Takara L Stanley, James M. Billingsley, Shannan J. Ho Sui, Meghan N. Feldpausch, Isabel Zheng, Kathleen E. Corey, Autumn Boutin, Colin M. Mcclure, Martin Torriani
    Abstract:

    NAFLD is a leading comorbidity in HIV with an exaggerated course compared to the general population. Tesamorelin has been demonstrated to reduce liver fat and prevent fibrosis progression in HIV-associated NAFLD. We further showed that Tesamorelin downregulated hepatic gene sets involved in inflammation, tissue repair, and cell division. Nonetheless, effects of Tesamorelin on individual plasma proteins pertaining to these pathways are not known. Leveraging our prior randomized-controlled trial and transcriptomic approach, we performed a focused assessment of 9 plasma proteins corresponding to top leading edge genes within differentially modulated gene sets. Tesamorelin led to significant reductions in vascular endothelial growth factor A (VEGFA, log_2-fold change − 0.20 ± 0.35 vs. 0.05 ± 0.34, P  = 0.02), transforming growth factor beta 1 (TGFB1, − 0.35 ± 0.56 vs. − 0.05 ± 0.43, P  = 0.05), and macrophage colony stimulating factor 1 (CSF1, − 0.17 ± 0.21 vs. 0.02 ± 0.20, P  = 0.004) versus placebo. Among Tesamorelin-treated participants, reductions in plasma VEGFA ( r  = 0.62, P  = 0.006) and CSF1 ( r  = 0.50, P  = 0.04) correlated with a decline in NAFLD activity score. Decreases in TGFB1 ( r  = 0.61, P  = 0.009) and CSF1 ( r  = 0.64, P  = 0.006) were associated with reduced gene-level fibrosis score. Tesamorelin suppressed key angiogenic, fibrogenic, and pro-inflammatory mediators. CSF1, a regulator of monocyte recruitment and activation, may serve as an innovative therapeutic target for NAFLD in HIV. Clinical Trials Registry Number: NCT02196831

  • Growth Hormone Releasing Hormone Reduces Circulating Markers of Immune Activation in Parallel with Effects on Hepatic Immune Pathways in Individuals with HIV-Infection and Nonalcoholic Fatty Liver Disease.
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2021
    Co-Authors: Takara L Stanley, Lindsay T. Fourman, James M. Billingsley, Meghan N. Feldpausch, Isabel Zheng, Chelsea S Pan, Autumn Boutin, Lai Ping Wong, Ruslan Sadreyev, Hang Lee
    Abstract:

    The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis modulates critical metabolic pathways; however, little is known regarding effects of augmenting pulsatile GH secretion on immune function in humans. This study used proteomics and gene set enrichment analysis to assess effects of a GH releasing hormone (GHRH) analog, Tesamorelin, on circulating immune markers and liver tissue in people with HIV (PWH) and NAFLD. 92 biomarkers associated with immunity, chemotaxis, and metabolism were measured in plasma samples from 61 PWH with NAFLD who participated in a double-blind, randomized trial of Tesamorelin versus placebo for 12 months. Gene set enrichment analysis was performed on serial liver biopsies targeted to immune pathways. Tesamorelin, compared to placebo, decreased interconnected proteins related to cytotoxic T-cell and monocyte activation. Circulating concentrations of 13 proteins were significantly decreased, and no proteins increased, by Tesamorelin. These included four chemokines (CCL3, CCL4, CCL13 [MCP4], IL8 [CXCL8]), two cytokines (IL-10 and CSF-1), and four T-cell associated molecules (CD8A, CRTAM, GZMA, ADGRG1), as well as ARG1, Gal-9, and HGF. Network analysis indicated close interaction among the gene pathways responsible for these proteins, with imputational analyses suggesting down regulation of a closely related cluster of immune pathways. Targeted transcriptomics using liver tissue confirmed a significant end-organ signal of down-regulated immune activation pathways. Long-term treatment with a GHRH analog reduced markers of T-cell and monocyte/macrophage activity, suggesting that augmentation of the GH axis may ameliorate immune activation in an HIV population with metabolic dysregulation, systemic and end organ inflammation. © The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  • Tesamorelin improves fat quality independent of changes in fat quantity
    AIDS, 2021
    Co-Authors: Jordan E Lake, L A Kristen, Kristine M Erlandson, Stefan Adrian, Gayane Yenokyan, Ann Scherzinger, Michael P Dube, Takara L Stanley, Steven K Grinspoon, Julian Falutz
    Abstract:

    OBJECTIVES : Fat quality and quantity may affect health similarly or differently. Fat quality can be assessed by measuring fat density on CT scan (greater density=smaller, higher quality adipocytes). We assessed the effects of Tesamorelin, a growth hormone-releasing hormone analogue that reduces visceral fat (VAT) quantity in some people living with HIV (PLWH), on fat density. DESIGN : Participants from two completed, placebo-controlled, randomized trials of Tesamorelin for central adiposity treatment in PLWH were included if they had either a clinical response to Tesamorelin (VAT decrease ≥8%, ≈70% of participants) or were placebo-treated. METHODS : CT VAT and subcutaneous fat (SAT) density (Hounsfield Units, HU) were measured by a central blinded reader.Results: Participants (193 responders, 148 placebo) were 87% male and 83% Caucasian. Baseline characteristics were similar across arms, including VAT (-91 HU both arms, p = 0.80) and SAT density (-94 HU Tesamorelin, -95 HU placebo, p = 0.29). Over 26 weeks, mean (SD) VAT and SAT density increased in Tesamorelin-treated participants only (VAT: + 6.2 (8.7) HU Tesamorelin, + 0.3 (4.2) HU placebo, p < 0.0001; SAT: + 4.0 (8.7) HU Tesamorelin, + 0.3 (4.8) HU placebo, p < 0.0001). The Tesamorelin effects persisted after controlling for baseline VAT or SAT HU and area, and VAT (+2.3 HU, 95% CI [4.5, 7.3], p = 0.001) or SAT (+3.5 HU, 95% CI [2.3, 4.7], p < 0.001) area change. CONCLUSIONS : In PLWH with central adiposity who experienced VAT quantity reductions on Tesamorelin, VAT and SAT density increased independent of changes in fat quantity, suggesting that Tesamorelin also improves VAT and SAT quality in this group.

  • Tesamorelin Improves Fat Quality Independent of Changes in Fat Quantity.
    AIDS (London England), 2021
    Co-Authors: Jordan E Lake, Kristine M Erlandson, Stefan Adrian, Gayane Yenokyan, Ann Scherzinger, Michael P Dube, Takara L Stanley, Steven K Grinspoon, Julian Falutz
    Abstract:

    OBJECTIVES : Fat quality and quantity may affect health similarly or differently. Fat quality can be assessed by measuring fat density on CT scan (greater density=smaller, higher quality adipocytes). We assessed the effects of Tesamorelin, a growth hormone-releasing hormone analogue that reduces visceral fat (VAT) quantity in some people living with HIV (PLWH), on fat density. DESIGN : Participants from two completed, placebo-controlled, randomized trials of Tesamorelin for central adiposity treatment in PLWH were included if they had either a clinical response to Tesamorelin (VAT decrease ≥8%, ≈70% of participants) or were placebo-treated. METHODS : CT VAT and subcutaneous fat (SAT) density (Hounsfield Units, HU) were measured by a central blinded reader.Results: Participants (193 responders, 148 placebo) were 87% male and 83% Caucasian. Baseline characteristics were similar across arms, including VAT (-91 HU both arms, p = 0.80) and SAT density (-94 HU Tesamorelin, -95 HU placebo, p = 0.29). Over 26 weeks, mean (SD) VAT and SAT density increased in Tesamorelin-treated participants only (VAT: + 6.2 (8.7) HU Tesamorelin, + 0.3 (4.2) HU placebo, p 

  • Clinical Predictors of Liver Fibrosis Presence and Progression in HIV-Associated NAFLD.
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2020
    Co-Authors: Lindsay T. Fourman, Takara L Stanley, Meghan N. Feldpausch, Julia B. Purdy, Isabel Zheng, Chelsea S Pan, Julia Aepfelbacher, Colleen Buckless, Andrew Tsao, Kathleen E. Corey
    Abstract:

    BACKGROUND Nonalcoholic fatty disease (NAFLD) affects over one-third of people living with HIV. Nonetheless, the natural history of HIV-associated NAFLD is poorly understood, including which patients are most likely to have a progressive disease course. METHODS We leveraged a randomized trial of the growth hormone-releasing hormone analogue Tesamorelin to treat NAFLD in HIV. Sixty-one participants with HIV-associated NAFLD were randomized to Tesamorelin or placebo for 12 months. Participants underwent liver biopsy at baseline and 12 months with histologic evaluation performed by an expert pathologist blinded to treatment. RESULTS In all participants with baseline biopsies (n=58), 43% had hepatic fibrosis. Individuals with fibrosis had higher NAFLD Activity Score (NAS) (3.6±2.0 vs. 2.0±0.8, P

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  • Delineating Tesamorelin response pathways in HIV-associated NAFLD using a targeted proteomic and transcriptomic approach
    Scientific Reports, 2021
    Co-Authors: Lindsay T. Fourman, Takara L Stanley, James M. Billingsley, Shannan J. Ho Sui, Meghan N. Feldpausch, Isabel Zheng, Kathleen E. Corey, Autumn Boutin, Colin M. Mcclure, Martin Torriani
    Abstract:

    NAFLD is a leading comorbidity in HIV with an exaggerated course compared to the general population. Tesamorelin has been demonstrated to reduce liver fat and prevent fibrosis progression in HIV-associated NAFLD. We further showed that Tesamorelin downregulated hepatic gene sets involved in inflammation, tissue repair, and cell division. Nonetheless, effects of Tesamorelin on individual plasma proteins pertaining to these pathways are not known. Leveraging our prior randomized-controlled trial and transcriptomic approach, we performed a focused assessment of 9 plasma proteins corresponding to top leading edge genes within differentially modulated gene sets. Tesamorelin led to significant reductions in vascular endothelial growth factor A (VEGFA, log_2-fold change − 0.20 ± 0.35 vs. 0.05 ± 0.34, P  = 0.02), transforming growth factor beta 1 (TGFB1, − 0.35 ± 0.56 vs. − 0.05 ± 0.43, P  = 0.05), and macrophage colony stimulating factor 1 (CSF1, − 0.17 ± 0.21 vs. 0.02 ± 0.20, P  = 0.004) versus placebo. Among Tesamorelin-treated participants, reductions in plasma VEGFA ( r  = 0.62, P  = 0.006) and CSF1 ( r  = 0.50, P  = 0.04) correlated with a decline in NAFLD activity score. Decreases in TGFB1 ( r  = 0.61, P  = 0.009) and CSF1 ( r  = 0.64, P  = 0.006) were associated with reduced gene-level fibrosis score. Tesamorelin suppressed key angiogenic, fibrogenic, and pro-inflammatory mediators. CSF1, a regulator of monocyte recruitment and activation, may serve as an innovative therapeutic target for NAFLD in HIV. Clinical Trials Registry Number: NCT02196831

  • Effects of Tesamorelin on hepatic transcriptomic signatures in HIV-associated NAFLD
    JCI insight, 2020
    Co-Authors: Lindsay T. Fourman, James M. Billingsley, George Agyapong, Shannan J. Ho Sui, Meghan N. Feldpausch, Julia B. Purdy, Isabel Zheng, Chelsea S Pan, Kathleen E. Corey, Martin Torriani
    Abstract:

    Nonalcoholic fatty liver disease (NAFLD) is a common comorbidity among people living with HIV that has a more aggressive course than NAFLD among the general population. In a recent randomized placebo-controlled trial, we demonstrated that the growth hormone-releasing hormone analog Tesamorelin reduced liver fat and prevented fibrosis progression in HIV-associated NAFLD over 1 year. As such, Tesamorelin is the first strategy that has shown to be effective against NAFLD among the population with HIV. The current study leveraged paired liver biopsy specimens from this trial to identify hepatic gene pathways that are differentially modulated by Tesamorelin versus placebo. Using gene set enrichment analysis, we found that Tesamorelin increased hepatic expression of hallmark gene sets involved in oxidative phosphorylation and decreased hepatic expression of gene sets contributing to inflammation, tissue repair, and cell division. Tesamorelin also reciprocally up- and downregulated curated gene sets associated with favorable and poor hepatocellular carcinoma prognosis, respectively. Notably, among Tesamorelin-treated participants, these changes in hepatic expression correlated with improved fibrosis-related gene score. Our findings inform our knowledge of the biology of pulsatile growth hormone action and provide a mechanistic basis for the observed clinical effects of Tesamorelin on the liver.

  • Comparison of visceral fat measurement by dual-energy X-ray absorptiometry to computed tomography in HIV and non-HIV
    Nutrition & Diabetes, 2019
    Co-Authors: Lindsay T. Fourman, Meghan N. Feldpausch, Martin Torriani, Emma M. Kileel, Jane Hubbard, Tara Holmes, Ellen J. Anderson, Sara E. Looby, Kathleen V. Fitch, Takara L Stanley
    Abstract:

    Background/Objectives Individuals with HIV are susceptible to visceral fat accumulation, which confers an increased risk of cardiometabolic disease. Advanced software to ascertain visceral fat content from dual-energy X-ray absorptiometry (DXA) has not been validated among this population. We sought to compare DXA with computed tomography (CT) in the measurement of visceral fat cross-sectional area (VAT) in HIV and non-HIV using Bland–Altman analyses. Subjects/Methods Data were combined from five previously conducted studies of individuals with HIV ( n  = 313) and controls without HIV ( n  = 144) in which paired DXA and CT scans were available. In cross-sectional analyses, DXA-VAT was compared with CT-VAT among participants with and without HIV. In longitudinal analyses, changes in VAT over time were compared between DXA and CT among participants with and without HIV receiving no intervention over 12 months and among individuals with HIV receiving Tesamorelin—a medication known to reduce VAT—over 6 months. Results In HIV, DXA underestimated VAT compared with CT among individuals with increased visceral adiposity. The measurement bias was −9 ± 47 cm^2 overall, but became progressively larger with greater VAT ( P  

  • Comparison of visceral fat measurement by dual-energy X-ray absorptiometry to computed tomography in HIV and non-HIV.
    Nutrition & diabetes, 2019
    Co-Authors: Lindsay T. Fourman, Meghan N. Feldpausch, Emma M. Kileel, Jane Hubbard, Ellen J. Anderson, Sara E. Looby, Kathleen V. Fitch, Tara M. Holmes, Martin Torriani
    Abstract:

    Individuals with HIV are susceptible to visceral fat accumulation, which confers an increased risk of cardiometabolic disease. Advanced software to ascertain visceral fat content from dual-energy X-ray absorptiometry (DXA) has not been validated among this population. We sought to compare DXA with computed tomography (CT) in the measurement of visceral fat cross-sectional area (VAT) in HIV and non-HIV using Bland–Altman analyses. Data were combined from five previously conducted studies of individuals with HIV (n = 313) and controls without HIV (n = 144) in which paired DXA and CT scans were available. In cross-sectional analyses, DXA-VAT was compared with CT-VAT among participants with and without HIV. In longitudinal analyses, changes in VAT over time were compared between DXA and CT among participants with and without HIV receiving no intervention over 12 months and among individuals with HIV receiving Tesamorelin—a medication known to reduce VAT—over 6 months. In HIV, DXA underestimated VAT compared with CT among individuals with increased visceral adiposity. The measurement bias was −9 ± 47 cm2 overall, but became progressively larger with greater VAT (P 

  • comparison of visceral fat measurement by dual energy x ray absorptiometry to computed tomography in hiv and non hiv
    Nutrition & Diabetes, 2019
    Co-Authors: Lindsay T. Fourman, Meghan N. Feldpausch, Martin Torriani, Emma M. Kileel, Jane Hubbard, Ellen J. Anderson, Sara E. Looby, Kathleen V. Fitch, Tara M. Holmes, Janet Lo
    Abstract:

    Individuals with HIV are susceptible to visceral fat accumulation, which confers an increased risk of cardiometabolic disease. Advanced software to ascertain visceral fat content from dual-energy X-ray absorptiometry (DXA) has not been validated among this population. We sought to compare DXA with computed tomography (CT) in the measurement of visceral fat cross-sectional area (VAT) in HIV and non-HIV using Bland–Altman analyses. Data were combined from five previously conducted studies of individuals with HIV (n = 313) and controls without HIV (n = 144) in which paired DXA and CT scans were available. In cross-sectional analyses, DXA-VAT was compared with CT-VAT among participants with and without HIV. In longitudinal analyses, changes in VAT over time were compared between DXA and CT among participants with and without HIV receiving no intervention over 12 months and among individuals with HIV receiving Tesamorelin—a medication known to reduce VAT—over 6 months. In HIV, DXA underestimated VAT compared with CT among individuals with increased visceral adiposity. The measurement bias was −9 ± 47 cm2 overall, but became progressively larger with greater VAT (P < 0.0001), e.g., −61 ± 58 cm2 among those with VAT ≥ 200 cm2. Sex-stratified analyses revealed that the relationship between VAT and measurement bias was especially pronounced in men (P < 0.0001). Longitudinally, DXA underestimated changes in VAT, particularly among those at the extremes of VAT gain or loss (P < 0.0001). In contrast to the cross-sectional findings, the tendency for DXA to underestimate longitudinal changes in VAT was evident in both men and women. Analogous findings were seen among controls in cross-sectional and longitudinal analyses. DXA underestimated VAT relative to CT in men with and without HIV, who had increased visceral adiposity. DXA also underestimated changes in VAT over time in men and women, irrespective of HIV status. DXA-VAT should be used with caution among both HIV and non-HIV-infected populations.