title: A placebo-controlled, dose-ranging study of a growth hormone releasing factor in HIV-infected patients with abdominal fat accumulation.
abstract: OBJECTIVE
  To investigate the effects of TH9507, a novel growth hormone releasing factor, on abdominal fat accumulation, metabolic and safety parameters in HIV-infected patients with central fat accumulation.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled trial enrolling 61 HIV-infected patients with increased waist circumference and waist-to-hip ratio. Participants were randomized to placebo or 1 or 2 mg TH9507 subcutaneously, once daily for 12 weeks. The primary outcome was change in abdominal fat, assessed by dual energy X-ray absorptiometry and cross-sectional computerized tomography scan. Secondary endpoints included change in insulin-like growth factor-I (IGF-I), metabolic, quality of life, and safety parameters.
  
  
  RESULTS
  TH9507 resulted in dose-related physiological increases in IGF-I (P < 0.01 for 1 mg (+48%) and 2 mg (+65%) versus placebo). Trunk fat decreased in the 2 mg group versus placebo (0.8, -4.6 and -9.2%; placebo, 1 and 2 mg, respectively, P = 0.014 for 2 mg versus placebo), without significant change in limb fat. Visceral fat (VAT) decreased most in the 2 mg group (-5.4, -3.6 and -15.7%; placebo, 1 and 2 mg, respectively) but this change was not significant versus placebo. Subcutaneous fat (SAT) was preserved and did not change between or within groups. Lean body mass and the ratio of VAT to SAT improved significantly in both treatment groups versus placebo. Triglyceride and the cholesterol to high-density lipoprotein ratio decreased significantly in the 2 mg group versus placebo. Treatment was generally well tolerated without changes in glucose.
  
  
  CONCLUSIONS
  TH9507 reduced truncal fat, improved the lipid profile and did not increase glucose levels in HIV-infected patients with central fat accumulation. TH9507 may be a beneficial treatment strategy in this population, but longer-term studies with more patients are needed to determine effects on VAT, treatment durability, and safety.
authors.affiliation: Montreal General Hospital Immuno-Deficiency Treatment Centre, McGill University Health Center, Montréal, Quebec, Canada.
authors.forename: Julian
authors.initials: J
authors.lastname: Falutz
authors.forename: Soraya
authors.initials: S
authors.lastname: Allas
authors.forename: Donald
authors.initials: D
authors.lastname: Kotler
authors.forename: Melanie
authors.initials: M
authors.lastname: Thompson
authors.forename: Polyxeni
authors.initials: P
authors.lastname: Koutkia
authors.forename: Jeanine
authors.initials: J
authors.lastname: Albu
authors.forename: Benoit
authors.initials: B
authors.lastname: Trottier
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
authors.forename: Pierre
authors.initials: P
authors.lastname: Cote
authors.forename: Thierry
authors.initials: T
authors.lastname: Abribat
authors.forename: Steven
authors.initials: S
authors.lastname: Grinspoon
mesh_terms: D000005:Abdomen; D000273:Adipose Tissue / Q000187:drug effects*; D000293:Adolescent; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage* / Q000031:analogs & derivatives; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism; D039682:HIV-Associated Lipodystrophy Syndrome; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage*; D016896:Treatment Outcome; D049629:Waist-Hip Ratio
chemical_list: D010455:Peptides; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone; C479538:tesamorelin