Dataset Information

Open-label trial of recombinant human insulin-like growth factor 1/recombinant human insulin-like growth factor binding protein 3 in myotonic dystrophy type 1.

ABSTRACT: To evaluate the safety and tolerability of recombinant human insulin-like growth factor 1 (rhIGF-1) complexed with IGF binding protein 3 (rhIGF-1/rhIGFBP-3) in patients with myotonic dystrophy type 1 (DM1).Open-label dose-escalation clinical trial.University medical center.Fifteen moderately affected ambulatory participants with genetically proven myotonic dystrophy type 1.Participants received escalating dosages of subcutaneous rhIGF-1/rhIGFBP-3 for 24 weeks followed by a 16-week washout period.Serial assessments of safety, muscle mass, muscle function, and metabolic state were performed. The primary outcome variable was the ability of participants to complete 24 weeks receiving rhIGF-1/ rhIGFBP-3 treatment.All participants tolerated rhIGF-1/rhIGFBP-3. There were no significant changes in muscle strength or functional outcomes measures. Lean body muscle mass measured by dual-energy x-ray absorptiometry increased by 1.95 kg (P < .001) after treatment. Participants also experienced a mean reduction in triglyceride levels of 47 mg/dL (P = .002), a mean increase in HDL levels of 5.0 mg/dL (P = .03), a mean reduction in hemoglobin A(1c) levels of 0.15% (P = .03), and a mean increase in testosterone level (in men) of 203 ng/dL (P = .002) while taking rhIGF-1/rhIGFBP-3. Mild reactions at the injection site occurred (9 participants), as did mild transient hypoglycemia (3), lightheadedness (2), and transient papilledema (1).Treatment with rhIGF-1/rhIGFBP-3 was generally well tolerated in patients with myotonic dystrophy type 1. Treatment with rhIGF-1/rhIGFBP-3 was associated with increased lean body mass and improvement in metabolism but not increased muscle strength or function. Larger randomized controlled trials would be needed to further evaluate the efficacy and safety of this medication in patients with neuromuscular disease.clinicaltrials.gov Identifier: NCT00233519.

SUBMITTER: Heatwole CR

PROVIDER: S-EPMC3374954 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Open-label trial of recombinant human insulin-like growth factor 1/recombinant human insulin-like growth factor binding protein 3 in myotonic dystrophy type 1.

Heatwole Chad R CR Eichinger Katy J KJ Friedman Deborah I DI Hilbert James E JE Jackson Carlayne E CE Logigian Eric L EL Martens William B WB McDermott Michael P MP Pandya Shree K SK Quinn Christine C Smirnow Alexis M AM Thornton Charles A CA Moxley Richard T RT

Archives of neurology 20100913 1

<h4>Objective</h4>To evaluate the safety and tolerability of recombinant human insulin-like growth factor 1 (rhIGF-1) complexed with IGF binding protein 3 (rhIGF-1/rhIGFBP-3) in patients with myotonic dystrophy type 1 (DM1).<h4>Design</h4>Open-label dose-escalation clinical trial.<h4>Setting</h4>University medical center.<h4>Participants</h4>Fifteen moderately affected ambulatory participants with genetically proven myotonic dystrophy type 1.<h4>Intervention</h4>Participants received escalating ...[more]

PMID: 20837825

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Project description:BackgroundPhelan-McDermid syndrome (PMS), also known as the 22q13. 3 deletion syndrome, is a rare neurodevelopmental syndrome with approximately 2,800 patients reported worldwide. Previous pilot study demonstrated that IGF-1 could significantly improve in both social impairment and restrictive behaviors of the patients. However, most of the patients in the developing countries like China cannot afford the high cost of using IGF-1. Our research team speculated that rhGH might serve as a low-cost and more accessible treatment for PMS. Therefore, the purpose of this open-label, cross-over, pilot study was to further investigate the safety and efficiency of rhGH in patients with PMS.MethodsA total of six children with PMS were enrolled in in this open-label, cross-over, pilot study. The children were randomly divided into two different groups. Group A received placebo followed by rhGH, while group B was treated with rhGH first. Neuropsychological and behavior assessments of the patients were performed before the stage I of study and 3 months after the intervention of stage I. After a 4-week period of washout, these assessments were conducted again before the stage II of study and 3 months after the intervention of stage II. Serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding-protein (IGFBP)-3 were also evaluated monthly during the intervention phases of the pilot study.ResultsCompared with the placebo, rhGH treatment significantly decreased subscale scores of GDS (P < 0.0085) and trended to improve the total scores of GDS (P < 0.05), while the total scores and subscale scores of SC-ABC significantly decreased (P < 0.0085) following 3-months rhGH treatment. The similar results were also observed in comparison with baseline. Compared with the baseline, the level of serum IGF-1 and IGFBP-3 increased significantly (P < 0.05) following 3-months rhGH treatment, while the placebo group had no significant impact on serum IGF-1 and IGFBP-3 (P > 0.05). One child developed skin allergy the day after the first rhGH treatment, which were resolved later.ConclusionsIn summary, this pilot study involving six PMS children patients reveals that rhGH has a positive treatment effect on PMS. These results encourage the undertaking of a large, randomized placebo-controlled trial to conclusively prove rhGH efficacy and tolerability in PMS, thereby promoting it as a low-cost, more accessible treatment for PMS, as compared to IGF-1.

Project description:A marked reduction in serum levels of bioactive insulin-like growth factor-I (IGF-I) has been observed in fasting hemodialysis (HD) patients during a 4-h HD session. The aim of the present study was to investigate the beneficial effect of hyperinsulinemia during HD on bioactive IGF-I and inflammatory biomarkers.In a randomized cross-over study, 11 non-diabetic HD patients received a standardised HD session with either: 1) no treatment, 2) glucose infusion (10% glucose, 2.5 mL/kg/h), or 3) glucose-insulin infusion (10% glucose added 30 IU NovoRapid® per litre, 2.5 mL/kg/h). Each experiment consisted of three periods: pre-HD (-120 to 0 min), HD (0 to 240 min), and post-HD (240 to 360 min). A meal was served at baseline (-120 min); infusions were administered from baseline to 240 min. The primary outcome was change in bioactive IGF-I during the experiment. Secondary outcomes were changes in high-sensitivity C-reactive protein, interleukin-1?, interleukin-6, and tumor necrosis factor ?. Comparisons were performed using mixed-model analysis of variance for repeated measures.From baseline to the end of study, no significant differences were observed in the changes in either serum bioactive IGF-I or total IGF-I between study days. Overall, serum bioactive IGF-I levels rose above baseline at 120 to 300 min with a maximum increase of 20% at 120 min (95% confidence interval (CI), 9 to 31%; p?<?0.001), whereas total IGF-I levels rose above baseline at 180 to 300 min with a maximum increase of 5% at 240 min (95% CI, 2 to 9%; p?=?0.004). A significant difference was observed in the changes in serum IGF-binding protein-1 (IGFBP-1) between study days (p?=?0.008), but differences were only significant in the post-HD period. From baseline to the end of HD, no significant difference was observed in the changes in serum IGFBP-1 levels between study days, and in this time period overall serum IGFBP-1 levels were below baseline at all time points with a maximum decrease of 51% at 180 min (95% CI, 45 to 57%; p?<?0.001). None of the investigated inflammatory biomarkers showed any differences in the changes over time between study days.Postprandial insulin secretion stimulated the IGF-system during HD with no further effect of adding glucose or glucose-insulin infusion. Hyperinsulinemia during HD had no effect on biomarkers of inflammation.ClinicalTrials.gov registry: NCT01209403.

Dataset Information

Open-label trial of recombinant human insulin-like growth factor 1/recombinant human insulin-like growth factor binding protein 3 in myotonic dystrophy type 1.

Publications

Open-label trial of recombinant human insulin-like growth factor 1/recombinant human insulin-like growth factor binding protein 3 in myotonic dystrophy type 1.

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