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

Objective: 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). Design: Open-label dose-escalation clinical trial. Setting: University medical center. Participants: Fifteen moderately affected ambulatory participants with genetically proven myotonic dystrophy type 1. Intervention: Participants received escalating dosages of subcutaneous rhIGF-1/rhIGFBP-3 for 24 weeks followed by a 16-week washout period. Main Outcome Measures: 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. Results: 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 A1c 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), light headedness (2), and transient papilledema (1). Conclusions: 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. Trial Registration: clinicaltrials.gov Identifier: NCT00233519.