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A randomized, placebo‐controlled trial of beloranib for the treatment of hypothalamic injury‐associated obesity
Author(s) -
Shoemaker Ashley,
Proietto Joseph,
Abuzzahab M. Jennifer,
Markovic Tania,
Malloy Jaret,
Kim Dennis D.
Publication year - 2017
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.12928
Subject(s) - medicine , placebo , tolerability , weight loss , clinical endpoint , adverse effect , obesity , randomized controlled trial , weight change , weight gain , surgery , anesthesia , body weight , alternative medicine , pathology
Aims Hypothalamic injury‐associated obesity ( HIAO ) results from damage to the hypothalamus that often occurs with surgical removal/radiation therapy of tumours in the hypothalamic region, such as craniopharyngioma. There is currently no rigorously studied pharmaceutical treatment for the intractable weight gain and cardiometabolic consequences that occur in patients with HIAO . We aimed to assess efficacy, safety and tolerability of beloranib treatment for 4 to 8 weeks in patients with HIAO . Materials and methods This P hase 2a, double‐blind, placebo‐controlled study included 14 patients with HIAO , randomized to receive beloranib 1.8 mg or placebo subcutaneously twice weekly for 4 weeks with an optional 4‐week open‐label extension in which all patients received beloranib. The primary endpoint was change in weight from baseline to Week 4. Results Participants were 64% female, with a mean ( SD ) age of 32 (9) years, BMI of 43 (7) kg/m 2 and weight of 126 (22) kg. Compared with placebo (N = 4), beloranib 1.8 mg (N = 8) resulted in a mean (95% CI ) difference in weight of −3.2 (−5.4, −0.9) kg after 4 weeks. Weight loss continued through the 8 weeks in patients randomized to beloranib (mean −6.2 [−8.2, −4.1] kg). Beloranib treatment was associated with improvements in high‐sensitivity CRP . Adverse events were mild to moderate. No patients who received beloranib discontinued treatment. Conclusion Beloranib treatment resulted in progressive weight loss in patients with HIAO that was comparable to that observed with beloranib in patients with exogenous obesity. These findings indicate a novel mechanism for treating obesity in patients with HIAO .