By Liz Highleyman

Previous studies have shown that human growth hormone (GH) may help reduce visceral abdominal fat accumulation in HIV positive patients taking antiretroviral therapy, but it can cause serious side effects including blood glucose abnormalities.

Researchers have therefore tested a growth hormone releasing factor (GHRF) analog, Theratechnologies' TH9507, which preliminary studies suggest may provide similar benefits with fewer adverse outcomes. Since GHRF stimulates the pituitary to produce GH, it raises GH levels in a pulsatile manner to levels within the natural physiological range without interfering with the normal endocrine feedback loop.

Julian Falutz presented data from a randomized, double-blind, placebo-controlled Phase III trial of TH9507 at the 14th Conference on Retroviruses and Opportunistic Infections held last week in Los Angeles.

The study included 412 HIV positive participants on HAART with documented abdominal fat accumulation related to antiretroviral therapy. Patients had well-controlled HIV disease, with viral loads below 10,000 copies/mL and CD4 counts above 100/cell.mm3.

Initially, 275 subjects were randomly assigned to receive 2 mg TH9507 once daily by subcutaneous injection, while 137 received placebo injections. After 26 weeks, participants crossed over to the other arm. Visceral abdominal fat (measured by CT scans), trunk fat (measured by DEXA), blood lipid levels, insulin growth factor 1 (IGF-1), and blood glucose and insulin levels were assessed throughout the study

Results

• At week 26, patients receiving TH9507 experienced a decrease in visceral abdominal fat, while those in the placebo group experienced a slight increase (-15.2 vs +5.0; P < 0.001).

• Trunk fat also decreased in the TH9507 arm (-1.0 vs +0.4; P < 0.001).

• TH9507 had a minimal effect on abdominal subcutaneous fat (+0.4 vs +1.8; P = 0.05) and limb fat (-0.0 vs +0.2; P = 0.01).

• Lipid profiles improved in the TH9507 arm, with patients experiencing significant decreases in triglyceride levels and cholesterol-to-HDL ratios.

• IGF-1 levels increased by 80% in the TH9507 arm, but remained within the normal physiological range.

• Blood glucose and insulin levels did not change significantly.

• TH9507 was well-tolerated overall, with a similar number of adverse events reported in the TH9507 and placebo arms.

• Headache and arthralgia (joint pain) were the only 2 adverse events reported by 10% or more patients in either arm.

• 6 patients (2%) in the TH9507 arm developed a hypersensitivity reaction.

• 5% discontinued with severe adverse events in the TH9507 arm, compared with 2% in the placebo arm.

Conclusion

The researchers conclude that TH9507 "may represent a novel treatment strategy for HIV patients with central fat accumulation, including those with impaired glucose homeostasis."

Montreal General Hospital, McGill University Health Center, Canada; Theratechnologies, Inc, Montreal, Canada; St Luke's Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, NY; Northstar Health Care, Chicago, IL; AIDS Research Alliance, West Hollywood, CA; Kaiser Foundation Research Inst, San Francisco, CA; and Massachusetts General Hospital, Boston, MA.

03/09/07

Reference
J Falutz, S Allas, K Blot. Effects of TH9507, a growth hormone releasing factor analog, on HIV-associated abdominal fat accumulation: a multicenter, double-blind placebo-controlled trial with 412 randomized patients. 14th Conference on Retroviruses and Opportunistic Infections. Los Angeles. February 25-28, 2007. Abstract 45LB (oral).

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