A placebo-controlled, dose-ranging study of a growth hormone releasing factor in HIV-infected patients with abdominal fat accumulation.
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.
Falutz
Julian
J
Montreal General Hospital Immuno-Deficiency Treatment Centre, McGill University Health Center, Montréal, Quebec, Canada.
Allas
Soraya
S
Kotler
Donald
D
Thompson
Melanie
M
Koutkia
Polyxeni
P
Albu
Jeanine
J
Trottier
Benoit
B
Routy
Jean-Pierre
JP
Cote
Pierre
P
Abribat
Thierry
T
Grinspoon
Steven
S
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
D010455:Peptides; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone; C479538:tesamorelin