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Gian Domenico Borasio - One of the best experts on this subject based on the ideXlab platform.
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Recombinant Human Insulin-like growth factor I (rhIGF-I) for amyotrophic lateral sclerosis/motor neuron disease.
The Cochrane database of systematic reviews, 2007Co-Authors: J D Mitchell, John H J Wokke, Gian Domenico BorasioAbstract:Trophic factors, including Recombinant Human Insulin-like growth factor I (rhIGF-I) are possible disease modifying therapies for amyotrophic lateral sclerosis. To examine the efficacy of Recombinant Human Insulin-like growth factor I in amyotrophic lateral sclerosis. We searched the Cochrane Neuromuscular Disease Group Trials Register (March 2006), MEDLINE (January 1966 to March 2006) and EMBASE (January 1980 to March 2006) and asked the authors of randomised clinical trials and manufacturers of Recombinant Human Insulin-like growth factor I. We considered all randomised controlled clinical trials involving rhIGF-I treatment of amyotrophic lateral sclerosis in adults with a clinical diagnosis of definite or probable amyotrophic lateral sclerosis according to the El Escorial Criteria. The primary outcome measure was change in Appel Amyotrophic Lateral Sclerosis Rating Scale (AALSRS) total score after nine months treatment and secondary outcome measures were change in AALSRS at 1, 2, 3, 4, 5, 6, 7, 8, 9 months, change in quality of life (Sickness Impact Profile scale), survival and adverse events. We identified three randomised clinical trials. Only two were included in the analysis. Each author graded the studies for methodological quality. Data were extracted and entered by the lead author and checked by the other two. Some missing data had to be regenerated by calculations based on ruler measurements of data presented in published graphs. In a European trial with 59 participants on placebo and 124 on rhIGF-I, 0.1 mg/kg/day the mean difference (MD) in change in AALSRS total score after nine months was -3.30 (95% confidence interval (CI) -8.68 to 2.08), non-significantly less in the treated than the placebo group. In a North American trial, in which 90 participants on placebo were compared with 89 on Recombinant Human Insulin-like growth factor I 0.05 mg/kg/day, and 87 participants on 0.1 mg/kg/day, the MD after nine months was -6.00 (95%CI -10.99 to -1.01), significantly less on treatment. The combined analysis from both randomised clinical trials showed a weighted mean difference after nine months of -4.75 (95% CI -8.41 to -1.09), a significant difference in favour of the treated group. The secondary outcome measures showed non-significant trends favouring rhIGF-I. Similarly the data with the 0.05 mg/kg/day dose showed trends favouring rhIGF-I at all time points but did not reach significance at the five per cent level at any point. There was an increased risk of injection site reactions with rhIGF-I (relative risk 2.53, 95% CI 1.40 to 4.59). The available randomised placebo controlled trials do not permit a definitive assessment of the clinical efficacy of rhIGF-I on ALS. More research is needed and one trial is in progress. Future trials should include survival as an outcome measure.
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Recombinant Human Insulin like growth factor i rhigf i for amyotrophic lateral sclerosis motor neuron disease
Cochrane Database of Systematic Reviews, 2002Co-Authors: J D Mitchell, John H J Wokke, Gian Domenico BorasioAbstract:BACKGROUND: Trophic factors, including Recombinant Human Insulin-like growth factor I have been postulated as possible disease modifying therapies for amyotrophic lateral sclerosis. Randomised clinical trials of Recombinant Human Insulin-like growth factor I in amyotrophic lateral sclerosis to date have yielded conflicting results. OBJECTIVES: The main objective of this review was to examine the efficacy of Recombinant Human Insulin-like growth factor I in amyotrophic lateral sclerosis. Occurrence of adverse events has also been reviewed. SEARCH STRATEGY: A search was carried out using the Cochrane Neuromuscular Disease Group register for randomised clinical trials of Recombinant Human Insulin-like growth factor I in amyotrophic lateral sclerosis. Enquiries were also made of authors of randomised clinical trials as well as the manufacturers of Recombinant Human Insulin-like growth factor I regarding any other randomised clinical trials which had not yet been published. SELECTION CRITERIA: Types of studies: all randomised controlled clinical trials involving Recombinant Human Insulin-like growth factor I treatment of amyotrophic lateral sclerosis. Types of participants: Adults with a clinical diagnosis of definite or probable amyotrophic lateral sclerosis according to the El Escorial Criteria. Types of interventions: Treatment with Recombinant Human Insulin-like growth factor I or placebo. Types of outcome measures: Primary: Change in Appel Amyotrophic Lateral Sclerosis Rating Scale (AALSRS) total score with 0.1mg/kg/day of Recombinant Human Insulin-like growth factor I after nine months treatment. Secondary: Change in AALSRS with Recombinant Human Insulin like growth factor I 0.1mg/kg/day and 0.05mg/kg/day at 1, 2, 3, 4, 5, 6, 7, 8, 9 months, change in quality of life (Sickness Impact Profile scale), survival and adverse events. DATA COLLECTION AND ANALYSIS: We identified two randomised clinical trials. Each reviewer graded them for methodological quality. Data were extracted and entered by the lead reviewer and checked by the other two. Some missing data had to be regenerated by calculations based on ruler measurements of data presented in published graphs. MAIN RESULTS: The primary outcome measure was change in disease progression as determined by the Appel ALS Rating Scale total score with 0.1 mg/kg/day of Recombinant Human Insulin-like growth factor I subcutaneously after nine months treatment. The level of significance was lower in the European trial which compared 59 patients on placebo with 124 on Insulin-like growth factor I 0.1 mg/kg/day (weighted mean difference -3.30, 95%CI -8.68 to 2.08) than in the North American trial which compared 90 patients on placebo with 89 on Recombinant Human Insulin-like growth factor I 0.05 mg/kg/day 89 patients and 87 patients on 0.1mg/kg/day (weighted mean difference -6.00, 95%CI -10.99 to -1.01). The combined analysis from both randomised clinical trials showed a weighted mean difference of -4.75 (95% CI -8.41 to -1.09) favouring the treated group. The secondary outcome measures showed similar trends favouring Recombinant Human Insulin-like growth factor I but these did not reach significance at the five per cent level. Similarly the data with the 0.05mg/kg/day dose showed trends favouring Recombinant Human Insulin-like growth factor I at all time points but did not reach significance at the five per cent level at any point. Evaluation of adverse events showed an increased risk of injection site reactions/inflammation with Recombinant Human Insulin-like growth factor I (relative risk 2.53, 95% CI 1.40 to 4.59). The drug was otherwise safe and well tolerated. REVIEWER'S CONCLUSIONS: Recombinant Human Insulin-like growth factor I may be modestly effective but the evidence currently available is insufficient for a definitive assessment. Further randomised clinical trials need to be done.
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The Cochrane Library - Recombinant Human Insulin-like growth factor I (rhIGF-I) for amyotrophic lateral sclerosis/motor neuron disease
The Cochrane database of systematic reviews, 2002Co-Authors: J D Mitchell, John H J Wokke, Gian Domenico BorasioAbstract:BACKGROUND: Trophic factors, including Recombinant Human Insulin-like growth factor I have been postulated as possible disease modifying therapies for amyotrophic lateral sclerosis. Randomised clinical trials of Recombinant Human Insulin-like growth factor I in amyotrophic lateral sclerosis to date have yielded conflicting results. OBJECTIVES: The main objective of this review was to examine the efficacy of Recombinant Human Insulin-like growth factor I in amyotrophic lateral sclerosis. Occurrence of adverse events has also been reviewed. SEARCH STRATEGY: A search was carried out using the Cochrane Neuromuscular Disease Group register for randomised clinical trials of Recombinant Human Insulin-like growth factor I in amyotrophic lateral sclerosis. Enquiries were also made of authors of randomised clinical trials as well as the manufacturers of Recombinant Human Insulin-like growth factor I regarding any other randomised clinical trials which had not yet been published. SELECTION CRITERIA: Types of studies: all randomised controlled clinical trials involving Recombinant Human Insulin-like growth factor I treatment of amyotrophic lateral sclerosis. Types of participants: Adults with a clinical diagnosis of definite or probable amyotrophic lateral sclerosis according to the El Escorial Criteria. Types of interventions: Treatment with Recombinant Human Insulin-like growth factor I or placebo. Types of outcome measures: Primary: Change in Appel Amyotrophic Lateral Sclerosis Rating Scale (AALSRS) total score with 0.1mg/kg/day of Recombinant Human Insulin-like growth factor I after nine months treatment. Secondary: Change in AALSRS with Recombinant Human Insulin like growth factor I 0.1mg/kg/day and 0.05mg/kg/day at 1, 2, 3, 4, 5, 6, 7, 8, 9 months, change in quality of life (Sickness Impact Profile scale), survival and adverse events. DATA COLLECTION AND ANALYSIS: We identified two randomised clinical trials. Each reviewer graded them for methodological quality. Data were extracted and entered by the lead reviewer and checked by the other two. Some missing data had to be regenerated by calculations based on ruler measurements of data presented in published graphs. MAIN RESULTS: The primary outcome measure was change in disease progression as determined by the Appel ALS Rating Scale total score with 0.1 mg/kg/day of Recombinant Human Insulin-like growth factor I subcutaneously after nine months treatment. The level of significance was lower in the European trial which compared 59 patients on placebo with 124 on Insulin-like growth factor I 0.1 mg/kg/day (weighted mean difference -3.30, 95%CI -8.68 to 2.08) than in the North American trial which compared 90 patients on placebo with 89 on Recombinant Human Insulin-like growth factor I 0.05 mg/kg/day 89 patients and 87 patients on 0.1mg/kg/day (weighted mean difference -6.00, 95%CI -10.99 to -1.01). The combined analysis from both randomised clinical trials showed a weighted mean difference of -4.75 (95% CI -8.41 to -1.09) favouring the treated group. The secondary outcome measures showed similar trends favouring Recombinant Human Insulin-like growth factor I but these did not reach significance at the five per cent level. Similarly the data with the 0.05mg/kg/day dose showed trends favouring Recombinant Human Insulin-like growth factor I at all time points but did not reach significance at the five per cent level at any point. Evaluation of adverse events showed an increased risk of injection site reactions/inflammation with Recombinant Human Insulin-like growth factor I (relative risk 2.53, 95% CI 1.40 to 4.59). The drug was otherwise safe and well tolerated. REVIEWER'S CONCLUSIONS: Recombinant Human Insulin-like growth factor I may be modestly effective but the evidence currently available is insufficient for a definitive assessment. Further randomised clinical trials need to be done.
Jeffrey L. Cleland - One of the best experts on this subject based on the ideXlab platform.
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sustained release of Recombinant Human Insulin like growth factor i for treatment of diabetes
Journal of Controlled Release, 2000Co-Authors: Xanthe M. Lam, Eileen T. Duenas, Ann L. Daugherty, Nancy Levin, Jeffrey L. ClelandAbstract:Recombinant Human Insulin-like growth factor-I (rhIGF-I) was found to improve glycemic control and enhance Insulin sensitivity in patients with a syndrome of severe Insulin resistance. Therefore, the protein may be considered as an alternative therapy in the treatment of diabetes when the patients become insensitive to Insulin treatment. Because the protein was administered twice per day in the clinical trials, a sustained release polylactic-co-glycolic acid (PLGA) formulation for rhIGF-I with low initial burst (<20%), maximum possible protein loading (15-20%) and a continuous release of 1-2 weeks may provide greater patient convenience and compliance. The protein was encapsulated in PLGA for sustained release using a spray freeze-drying technique. Formulation parameters such as protein loading, polymer end group, and the presence of zinc carbonate were studied for their effects on in vitro release of rhIGF-I from PLGA microspheres. As the protein loading was increased, the initial burst increased. Due to the hydrophilic properties of the polymers, rhIGF-I encapsulated in unblocked PLGA (free acid end groups) gave a lower initial burst and a more steady-state release profile than the blocked PLGA (hydrocarbon end groups) with the same protein loading and PLGA molecular weight. At 15% w/w protein loading, the addition of 6% w/w zinc carbonate as a protein release modifier to the unblocked PLGA (12 kDa) decreased the initial burst of rhIGF-I. Therefore, a formulation consisting of 15% rhIGF-I and 6% zinc carbonate in 12 kDa, unblocked 50:50 PLGA can provide the required release characteristics in vitro. Rat studies revealed that rhIGF-I in this formulation was released in vivo at a rate which was comparable to that observed in vitro. These studies demonstrate the potential for a sustained release, 14-day formulation for rhIGF-I.
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Sustained release of Recombinant Human Insulin-like growth factor-I for treatment of diabetes.
Journal of Controlled Release, 2000Co-Authors: Xanthe M. Lam, Eileen T. Duenas, Ann L. Daugherty, Nancy Levin, Jeffrey L. ClelandAbstract:Recombinant Human Insulin-like growth factor-I (rhIGF-I) was found to improve glycemic control and enhance Insulin sensitivity in patients with a syndrome of severe Insulin resistance. Therefore, the protein may be considered as an alternative therapy in the treatment of diabetes when the patients become insensitive to Insulin treatment. Because the protein was administered twice per day in the clinical trials, a sustained release polylactic-co-glycolic acid (PLGA) formulation for rhIGF-I with low initial burst (
J D Mitchell - One of the best experts on this subject based on the ideXlab platform.
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Recombinant Human Insulin-like growth factor I (rhIGF-I) for amyotrophic lateral sclerosis/motor neuron disease.
The Cochrane database of systematic reviews, 2007Co-Authors: J D Mitchell, John H J Wokke, Gian Domenico BorasioAbstract:Trophic factors, including Recombinant Human Insulin-like growth factor I (rhIGF-I) are possible disease modifying therapies for amyotrophic lateral sclerosis. To examine the efficacy of Recombinant Human Insulin-like growth factor I in amyotrophic lateral sclerosis. We searched the Cochrane Neuromuscular Disease Group Trials Register (March 2006), MEDLINE (January 1966 to March 2006) and EMBASE (January 1980 to March 2006) and asked the authors of randomised clinical trials and manufacturers of Recombinant Human Insulin-like growth factor I. We considered all randomised controlled clinical trials involving rhIGF-I treatment of amyotrophic lateral sclerosis in adults with a clinical diagnosis of definite or probable amyotrophic lateral sclerosis according to the El Escorial Criteria. The primary outcome measure was change in Appel Amyotrophic Lateral Sclerosis Rating Scale (AALSRS) total score after nine months treatment and secondary outcome measures were change in AALSRS at 1, 2, 3, 4, 5, 6, 7, 8, 9 months, change in quality of life (Sickness Impact Profile scale), survival and adverse events. We identified three randomised clinical trials. Only two were included in the analysis. Each author graded the studies for methodological quality. Data were extracted and entered by the lead author and checked by the other two. Some missing data had to be regenerated by calculations based on ruler measurements of data presented in published graphs. In a European trial with 59 participants on placebo and 124 on rhIGF-I, 0.1 mg/kg/day the mean difference (MD) in change in AALSRS total score after nine months was -3.30 (95% confidence interval (CI) -8.68 to 2.08), non-significantly less in the treated than the placebo group. In a North American trial, in which 90 participants on placebo were compared with 89 on Recombinant Human Insulin-like growth factor I 0.05 mg/kg/day, and 87 participants on 0.1 mg/kg/day, the MD after nine months was -6.00 (95%CI -10.99 to -1.01), significantly less on treatment. The combined analysis from both randomised clinical trials showed a weighted mean difference after nine months of -4.75 (95% CI -8.41 to -1.09), a significant difference in favour of the treated group. The secondary outcome measures showed non-significant trends favouring rhIGF-I. Similarly the data with the 0.05 mg/kg/day dose showed trends favouring rhIGF-I at all time points but did not reach significance at the five per cent level at any point. There was an increased risk of injection site reactions with rhIGF-I (relative risk 2.53, 95% CI 1.40 to 4.59). The available randomised placebo controlled trials do not permit a definitive assessment of the clinical efficacy of rhIGF-I on ALS. More research is needed and one trial is in progress. Future trials should include survival as an outcome measure.
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Recombinant Human Insulin like growth factor i rhigf i for amyotrophic lateral sclerosis motor neuron disease
Cochrane Database of Systematic Reviews, 2002Co-Authors: J D Mitchell, John H J Wokke, Gian Domenico BorasioAbstract:BACKGROUND: Trophic factors, including Recombinant Human Insulin-like growth factor I have been postulated as possible disease modifying therapies for amyotrophic lateral sclerosis. Randomised clinical trials of Recombinant Human Insulin-like growth factor I in amyotrophic lateral sclerosis to date have yielded conflicting results. OBJECTIVES: The main objective of this review was to examine the efficacy of Recombinant Human Insulin-like growth factor I in amyotrophic lateral sclerosis. Occurrence of adverse events has also been reviewed. SEARCH STRATEGY: A search was carried out using the Cochrane Neuromuscular Disease Group register for randomised clinical trials of Recombinant Human Insulin-like growth factor I in amyotrophic lateral sclerosis. Enquiries were also made of authors of randomised clinical trials as well as the manufacturers of Recombinant Human Insulin-like growth factor I regarding any other randomised clinical trials which had not yet been published. SELECTION CRITERIA: Types of studies: all randomised controlled clinical trials involving Recombinant Human Insulin-like growth factor I treatment of amyotrophic lateral sclerosis. Types of participants: Adults with a clinical diagnosis of definite or probable amyotrophic lateral sclerosis according to the El Escorial Criteria. Types of interventions: Treatment with Recombinant Human Insulin-like growth factor I or placebo. Types of outcome measures: Primary: Change in Appel Amyotrophic Lateral Sclerosis Rating Scale (AALSRS) total score with 0.1mg/kg/day of Recombinant Human Insulin-like growth factor I after nine months treatment. Secondary: Change in AALSRS with Recombinant Human Insulin like growth factor I 0.1mg/kg/day and 0.05mg/kg/day at 1, 2, 3, 4, 5, 6, 7, 8, 9 months, change in quality of life (Sickness Impact Profile scale), survival and adverse events. DATA COLLECTION AND ANALYSIS: We identified two randomised clinical trials. Each reviewer graded them for methodological quality. Data were extracted and entered by the lead reviewer and checked by the other two. Some missing data had to be regenerated by calculations based on ruler measurements of data presented in published graphs. MAIN RESULTS: The primary outcome measure was change in disease progression as determined by the Appel ALS Rating Scale total score with 0.1 mg/kg/day of Recombinant Human Insulin-like growth factor I subcutaneously after nine months treatment. The level of significance was lower in the European trial which compared 59 patients on placebo with 124 on Insulin-like growth factor I 0.1 mg/kg/day (weighted mean difference -3.30, 95%CI -8.68 to 2.08) than in the North American trial which compared 90 patients on placebo with 89 on Recombinant Human Insulin-like growth factor I 0.05 mg/kg/day 89 patients and 87 patients on 0.1mg/kg/day (weighted mean difference -6.00, 95%CI -10.99 to -1.01). The combined analysis from both randomised clinical trials showed a weighted mean difference of -4.75 (95% CI -8.41 to -1.09) favouring the treated group. The secondary outcome measures showed similar trends favouring Recombinant Human Insulin-like growth factor I but these did not reach significance at the five per cent level. Similarly the data with the 0.05mg/kg/day dose showed trends favouring Recombinant Human Insulin-like growth factor I at all time points but did not reach significance at the five per cent level at any point. Evaluation of adverse events showed an increased risk of injection site reactions/inflammation with Recombinant Human Insulin-like growth factor I (relative risk 2.53, 95% CI 1.40 to 4.59). The drug was otherwise safe and well tolerated. REVIEWER'S CONCLUSIONS: Recombinant Human Insulin-like growth factor I may be modestly effective but the evidence currently available is insufficient for a definitive assessment. Further randomised clinical trials need to be done.
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The Cochrane Library - Recombinant Human Insulin-like growth factor I (rhIGF-I) for amyotrophic lateral sclerosis/motor neuron disease
The Cochrane database of systematic reviews, 2002Co-Authors: J D Mitchell, John H J Wokke, Gian Domenico BorasioAbstract:BACKGROUND: Trophic factors, including Recombinant Human Insulin-like growth factor I have been postulated as possible disease modifying therapies for amyotrophic lateral sclerosis. Randomised clinical trials of Recombinant Human Insulin-like growth factor I in amyotrophic lateral sclerosis to date have yielded conflicting results. OBJECTIVES: The main objective of this review was to examine the efficacy of Recombinant Human Insulin-like growth factor I in amyotrophic lateral sclerosis. Occurrence of adverse events has also been reviewed. SEARCH STRATEGY: A search was carried out using the Cochrane Neuromuscular Disease Group register for randomised clinical trials of Recombinant Human Insulin-like growth factor I in amyotrophic lateral sclerosis. Enquiries were also made of authors of randomised clinical trials as well as the manufacturers of Recombinant Human Insulin-like growth factor I regarding any other randomised clinical trials which had not yet been published. SELECTION CRITERIA: Types of studies: all randomised controlled clinical trials involving Recombinant Human Insulin-like growth factor I treatment of amyotrophic lateral sclerosis. Types of participants: Adults with a clinical diagnosis of definite or probable amyotrophic lateral sclerosis according to the El Escorial Criteria. Types of interventions: Treatment with Recombinant Human Insulin-like growth factor I or placebo. Types of outcome measures: Primary: Change in Appel Amyotrophic Lateral Sclerosis Rating Scale (AALSRS) total score with 0.1mg/kg/day of Recombinant Human Insulin-like growth factor I after nine months treatment. Secondary: Change in AALSRS with Recombinant Human Insulin like growth factor I 0.1mg/kg/day and 0.05mg/kg/day at 1, 2, 3, 4, 5, 6, 7, 8, 9 months, change in quality of life (Sickness Impact Profile scale), survival and adverse events. DATA COLLECTION AND ANALYSIS: We identified two randomised clinical trials. Each reviewer graded them for methodological quality. Data were extracted and entered by the lead reviewer and checked by the other two. Some missing data had to be regenerated by calculations based on ruler measurements of data presented in published graphs. MAIN RESULTS: The primary outcome measure was change in disease progression as determined by the Appel ALS Rating Scale total score with 0.1 mg/kg/day of Recombinant Human Insulin-like growth factor I subcutaneously after nine months treatment. The level of significance was lower in the European trial which compared 59 patients on placebo with 124 on Insulin-like growth factor I 0.1 mg/kg/day (weighted mean difference -3.30, 95%CI -8.68 to 2.08) than in the North American trial which compared 90 patients on placebo with 89 on Recombinant Human Insulin-like growth factor I 0.05 mg/kg/day 89 patients and 87 patients on 0.1mg/kg/day (weighted mean difference -6.00, 95%CI -10.99 to -1.01). The combined analysis from both randomised clinical trials showed a weighted mean difference of -4.75 (95% CI -8.41 to -1.09) favouring the treated group. The secondary outcome measures showed similar trends favouring Recombinant Human Insulin-like growth factor I but these did not reach significance at the five per cent level. Similarly the data with the 0.05mg/kg/day dose showed trends favouring Recombinant Human Insulin-like growth factor I at all time points but did not reach significance at the five per cent level at any point. Evaluation of adverse events showed an increased risk of injection site reactions/inflammation with Recombinant Human Insulin-like growth factor I (relative risk 2.53, 95% CI 1.40 to 4.59). The drug was otherwise safe and well tolerated. REVIEWER'S CONCLUSIONS: Recombinant Human Insulin-like growth factor I may be modestly effective but the evidence currently available is insufficient for a definitive assessment. Further randomised clinical trials need to be done.
Xanthe M. Lam - One of the best experts on this subject based on the ideXlab platform.
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sustained release of Recombinant Human Insulin like growth factor i for treatment of diabetes
Journal of Controlled Release, 2000Co-Authors: Xanthe M. Lam, Eileen T. Duenas, Ann L. Daugherty, Nancy Levin, Jeffrey L. ClelandAbstract:Recombinant Human Insulin-like growth factor-I (rhIGF-I) was found to improve glycemic control and enhance Insulin sensitivity in patients with a syndrome of severe Insulin resistance. Therefore, the protein may be considered as an alternative therapy in the treatment of diabetes when the patients become insensitive to Insulin treatment. Because the protein was administered twice per day in the clinical trials, a sustained release polylactic-co-glycolic acid (PLGA) formulation for rhIGF-I with low initial burst (<20%), maximum possible protein loading (15-20%) and a continuous release of 1-2 weeks may provide greater patient convenience and compliance. The protein was encapsulated in PLGA for sustained release using a spray freeze-drying technique. Formulation parameters such as protein loading, polymer end group, and the presence of zinc carbonate were studied for their effects on in vitro release of rhIGF-I from PLGA microspheres. As the protein loading was increased, the initial burst increased. Due to the hydrophilic properties of the polymers, rhIGF-I encapsulated in unblocked PLGA (free acid end groups) gave a lower initial burst and a more steady-state release profile than the blocked PLGA (hydrocarbon end groups) with the same protein loading and PLGA molecular weight. At 15% w/w protein loading, the addition of 6% w/w zinc carbonate as a protein release modifier to the unblocked PLGA (12 kDa) decreased the initial burst of rhIGF-I. Therefore, a formulation consisting of 15% rhIGF-I and 6% zinc carbonate in 12 kDa, unblocked 50:50 PLGA can provide the required release characteristics in vitro. Rat studies revealed that rhIGF-I in this formulation was released in vivo at a rate which was comparable to that observed in vitro. These studies demonstrate the potential for a sustained release, 14-day formulation for rhIGF-I.
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Sustained release of Recombinant Human Insulin-like growth factor-I for treatment of diabetes.
Journal of Controlled Release, 2000Co-Authors: Xanthe M. Lam, Eileen T. Duenas, Ann L. Daugherty, Nancy Levin, Jeffrey L. ClelandAbstract:Recombinant Human Insulin-like growth factor-I (rhIGF-I) was found to improve glycemic control and enhance Insulin sensitivity in patients with a syndrome of severe Insulin resistance. Therefore, the protein may be considered as an alternative therapy in the treatment of diabetes when the patients become insensitive to Insulin treatment. Because the protein was administered twice per day in the clinical trials, a sustained release polylactic-co-glycolic acid (PLGA) formulation for rhIGF-I with low initial burst (
John H J Wokke - One of the best experts on this subject based on the ideXlab platform.
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Recombinant Human Insulin-like growth factor I (rhIGF-I) for amyotrophic lateral sclerosis/motor neuron disease.
The Cochrane database of systematic reviews, 2007Co-Authors: J D Mitchell, John H J Wokke, Gian Domenico BorasioAbstract:Trophic factors, including Recombinant Human Insulin-like growth factor I (rhIGF-I) are possible disease modifying therapies for amyotrophic lateral sclerosis. To examine the efficacy of Recombinant Human Insulin-like growth factor I in amyotrophic lateral sclerosis. We searched the Cochrane Neuromuscular Disease Group Trials Register (March 2006), MEDLINE (January 1966 to March 2006) and EMBASE (January 1980 to March 2006) and asked the authors of randomised clinical trials and manufacturers of Recombinant Human Insulin-like growth factor I. We considered all randomised controlled clinical trials involving rhIGF-I treatment of amyotrophic lateral sclerosis in adults with a clinical diagnosis of definite or probable amyotrophic lateral sclerosis according to the El Escorial Criteria. The primary outcome measure was change in Appel Amyotrophic Lateral Sclerosis Rating Scale (AALSRS) total score after nine months treatment and secondary outcome measures were change in AALSRS at 1, 2, 3, 4, 5, 6, 7, 8, 9 months, change in quality of life (Sickness Impact Profile scale), survival and adverse events. We identified three randomised clinical trials. Only two were included in the analysis. Each author graded the studies for methodological quality. Data were extracted and entered by the lead author and checked by the other two. Some missing data had to be regenerated by calculations based on ruler measurements of data presented in published graphs. In a European trial with 59 participants on placebo and 124 on rhIGF-I, 0.1 mg/kg/day the mean difference (MD) in change in AALSRS total score after nine months was -3.30 (95% confidence interval (CI) -8.68 to 2.08), non-significantly less in the treated than the placebo group. In a North American trial, in which 90 participants on placebo were compared with 89 on Recombinant Human Insulin-like growth factor I 0.05 mg/kg/day, and 87 participants on 0.1 mg/kg/day, the MD after nine months was -6.00 (95%CI -10.99 to -1.01), significantly less on treatment. The combined analysis from both randomised clinical trials showed a weighted mean difference after nine months of -4.75 (95% CI -8.41 to -1.09), a significant difference in favour of the treated group. The secondary outcome measures showed non-significant trends favouring rhIGF-I. Similarly the data with the 0.05 mg/kg/day dose showed trends favouring rhIGF-I at all time points but did not reach significance at the five per cent level at any point. There was an increased risk of injection site reactions with rhIGF-I (relative risk 2.53, 95% CI 1.40 to 4.59). The available randomised placebo controlled trials do not permit a definitive assessment of the clinical efficacy of rhIGF-I on ALS. More research is needed and one trial is in progress. Future trials should include survival as an outcome measure.
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Recombinant Human Insulin like growth factor i rhigf i for amyotrophic lateral sclerosis motor neuron disease
Cochrane Database of Systematic Reviews, 2002Co-Authors: J D Mitchell, John H J Wokke, Gian Domenico BorasioAbstract:BACKGROUND: Trophic factors, including Recombinant Human Insulin-like growth factor I have been postulated as possible disease modifying therapies for amyotrophic lateral sclerosis. Randomised clinical trials of Recombinant Human Insulin-like growth factor I in amyotrophic lateral sclerosis to date have yielded conflicting results. OBJECTIVES: The main objective of this review was to examine the efficacy of Recombinant Human Insulin-like growth factor I in amyotrophic lateral sclerosis. Occurrence of adverse events has also been reviewed. SEARCH STRATEGY: A search was carried out using the Cochrane Neuromuscular Disease Group register for randomised clinical trials of Recombinant Human Insulin-like growth factor I in amyotrophic lateral sclerosis. Enquiries were also made of authors of randomised clinical trials as well as the manufacturers of Recombinant Human Insulin-like growth factor I regarding any other randomised clinical trials which had not yet been published. SELECTION CRITERIA: Types of studies: all randomised controlled clinical trials involving Recombinant Human Insulin-like growth factor I treatment of amyotrophic lateral sclerosis. Types of participants: Adults with a clinical diagnosis of definite or probable amyotrophic lateral sclerosis according to the El Escorial Criteria. Types of interventions: Treatment with Recombinant Human Insulin-like growth factor I or placebo. Types of outcome measures: Primary: Change in Appel Amyotrophic Lateral Sclerosis Rating Scale (AALSRS) total score with 0.1mg/kg/day of Recombinant Human Insulin-like growth factor I after nine months treatment. Secondary: Change in AALSRS with Recombinant Human Insulin like growth factor I 0.1mg/kg/day and 0.05mg/kg/day at 1, 2, 3, 4, 5, 6, 7, 8, 9 months, change in quality of life (Sickness Impact Profile scale), survival and adverse events. DATA COLLECTION AND ANALYSIS: We identified two randomised clinical trials. Each reviewer graded them for methodological quality. Data were extracted and entered by the lead reviewer and checked by the other two. Some missing data had to be regenerated by calculations based on ruler measurements of data presented in published graphs. MAIN RESULTS: The primary outcome measure was change in disease progression as determined by the Appel ALS Rating Scale total score with 0.1 mg/kg/day of Recombinant Human Insulin-like growth factor I subcutaneously after nine months treatment. The level of significance was lower in the European trial which compared 59 patients on placebo with 124 on Insulin-like growth factor I 0.1 mg/kg/day (weighted mean difference -3.30, 95%CI -8.68 to 2.08) than in the North American trial which compared 90 patients on placebo with 89 on Recombinant Human Insulin-like growth factor I 0.05 mg/kg/day 89 patients and 87 patients on 0.1mg/kg/day (weighted mean difference -6.00, 95%CI -10.99 to -1.01). The combined analysis from both randomised clinical trials showed a weighted mean difference of -4.75 (95% CI -8.41 to -1.09) favouring the treated group. The secondary outcome measures showed similar trends favouring Recombinant Human Insulin-like growth factor I but these did not reach significance at the five per cent level. Similarly the data with the 0.05mg/kg/day dose showed trends favouring Recombinant Human Insulin-like growth factor I at all time points but did not reach significance at the five per cent level at any point. Evaluation of adverse events showed an increased risk of injection site reactions/inflammation with Recombinant Human Insulin-like growth factor I (relative risk 2.53, 95% CI 1.40 to 4.59). The drug was otherwise safe and well tolerated. REVIEWER'S CONCLUSIONS: Recombinant Human Insulin-like growth factor I may be modestly effective but the evidence currently available is insufficient for a definitive assessment. Further randomised clinical trials need to be done.
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The Cochrane Library - Recombinant Human Insulin-like growth factor I (rhIGF-I) for amyotrophic lateral sclerosis/motor neuron disease
The Cochrane database of systematic reviews, 2002Co-Authors: J D Mitchell, John H J Wokke, Gian Domenico BorasioAbstract:BACKGROUND: Trophic factors, including Recombinant Human Insulin-like growth factor I have been postulated as possible disease modifying therapies for amyotrophic lateral sclerosis. Randomised clinical trials of Recombinant Human Insulin-like growth factor I in amyotrophic lateral sclerosis to date have yielded conflicting results. OBJECTIVES: The main objective of this review was to examine the efficacy of Recombinant Human Insulin-like growth factor I in amyotrophic lateral sclerosis. Occurrence of adverse events has also been reviewed. SEARCH STRATEGY: A search was carried out using the Cochrane Neuromuscular Disease Group register for randomised clinical trials of Recombinant Human Insulin-like growth factor I in amyotrophic lateral sclerosis. Enquiries were also made of authors of randomised clinical trials as well as the manufacturers of Recombinant Human Insulin-like growth factor I regarding any other randomised clinical trials which had not yet been published. SELECTION CRITERIA: Types of studies: all randomised controlled clinical trials involving Recombinant Human Insulin-like growth factor I treatment of amyotrophic lateral sclerosis. Types of participants: Adults with a clinical diagnosis of definite or probable amyotrophic lateral sclerosis according to the El Escorial Criteria. Types of interventions: Treatment with Recombinant Human Insulin-like growth factor I or placebo. Types of outcome measures: Primary: Change in Appel Amyotrophic Lateral Sclerosis Rating Scale (AALSRS) total score with 0.1mg/kg/day of Recombinant Human Insulin-like growth factor I after nine months treatment. Secondary: Change in AALSRS with Recombinant Human Insulin like growth factor I 0.1mg/kg/day and 0.05mg/kg/day at 1, 2, 3, 4, 5, 6, 7, 8, 9 months, change in quality of life (Sickness Impact Profile scale), survival and adverse events. DATA COLLECTION AND ANALYSIS: We identified two randomised clinical trials. Each reviewer graded them for methodological quality. Data were extracted and entered by the lead reviewer and checked by the other two. Some missing data had to be regenerated by calculations based on ruler measurements of data presented in published graphs. MAIN RESULTS: The primary outcome measure was change in disease progression as determined by the Appel ALS Rating Scale total score with 0.1 mg/kg/day of Recombinant Human Insulin-like growth factor I subcutaneously after nine months treatment. The level of significance was lower in the European trial which compared 59 patients on placebo with 124 on Insulin-like growth factor I 0.1 mg/kg/day (weighted mean difference -3.30, 95%CI -8.68 to 2.08) than in the North American trial which compared 90 patients on placebo with 89 on Recombinant Human Insulin-like growth factor I 0.05 mg/kg/day 89 patients and 87 patients on 0.1mg/kg/day (weighted mean difference -6.00, 95%CI -10.99 to -1.01). The combined analysis from both randomised clinical trials showed a weighted mean difference of -4.75 (95% CI -8.41 to -1.09) favouring the treated group. The secondary outcome measures showed similar trends favouring Recombinant Human Insulin-like growth factor I but these did not reach significance at the five per cent level. Similarly the data with the 0.05mg/kg/day dose showed trends favouring Recombinant Human Insulin-like growth factor I at all time points but did not reach significance at the five per cent level at any point. Evaluation of adverse events showed an increased risk of injection site reactions/inflammation with Recombinant Human Insulin-like growth factor I (relative risk 2.53, 95% CI 1.40 to 4.59). The drug was otherwise safe and well tolerated. REVIEWER'S CONCLUSIONS: Recombinant Human Insulin-like growth factor I may be modestly effective but the evidence currently available is insufficient for a definitive assessment. Further randomised clinical trials need to be done.