WEDNESDAY, Dec. 5, 2007 (HealthDay News) -- An investigational drug may be the first safe, reliable means of easing a disorder that leads to unsightly "humps" of body fat and boosts the heart risks of HIV patients.
People taking the drug tesamorelin for 26 weeks showed a 15 percent decline in dangerous visceral fat accumulating around their organs, as well as an improvement in related heart risk factors. They also reported psychological gains in terms of body image, said researchers reporting in the Dec. 6 issue of the New England Journal of Medicine.
While the long-term safety of tesamorelin remains unanswered, "we are very hopeful about this -- this could be one of the first major therapies in this regard," said the study's senior author, Dr. Steven Grinspoon, an associate professor of medicine at Harvard Medical School.
The study was funded by Theratechnologies, the Canadian company that is developing the drug.
Abnormalities in metabolism and fat deposits ("lipodystrophy") are common in people who take powerful antiretroviral drugs to help suppress HIV. "It's fairly prevalent in over half of the patients," said Grinspoon, who is also director of the Program in Nutritional Metabolism at Massachusetts General Hospital.
For reasons that remain unclear, HIV drug therapy often reduces normal fat levels in the arms and the legs while boosting it in other areas, including unsightly "humps" at the shoulder. The drugs can also shift fat deposition to deep in the abdomen, around the organs. This visceral fat is strongly associated with an increase in blood levels of cholesterol and triglycerides, as well as insulin resistance, which can lead to diabetes.
"All of that conspires to increase the risk of vascular disease," explained Dr. Marc Blackman, associate chief of staff for research and development at the VA Medical Center in Washington, D.C.
So far, no intervention has really helped correct this disorder, said Blackman, who also authored an accompanying commentary in the journal.
"Exercise, diet, diabetes or cholesterol drugs -- none of them has been shown to be terribly effective," he said.
Because fat deposition is linked to the release of growth hormone from the pituitary gland, researchers have tried to give patients human growth hormone. Unfortunately, the side effects from the therapy were just too onerous for most patients to bear, Grinspoon said.
Enter tesamorelin, a synthetic version of a hormone that stimulates the patient's pituitary to produce its own natural growth hormone.
In the phase III trial, Grinspoon's group had 412 HIV patients (86 percent men) with lipodystrophy receive a daily injection of 2 milligrams of tesamorelin or a placebo for 26 weeks. They then used CT scans to track changes in visceral fat over six months, and measured patients' cholesterol and triglyceride levels.
"We had a very significant reduction in visceral fat on the order of 15 percent within the group, and all of the lipid [blood fat] parameters improved -- triglycerides, cholesterol, LDL cholesterol alone," Grinspoon said. All of this occurred without unhealthy alterations in blood sugar (something seen with growth hormone therapy). Patients also reported "improvement in body image, they felt less distressed," Grinspoon said.
Side effects noted in the growth hormone studies, such as swelling and joint pain, were not seen in this trial, he added. "We basically achieved a generally similar reduction in visceral adiposity -- something very close -- without the side effects," Grinspoon said.
The study has since been extended, he added, "suggesting that [tesamorelin] is relatively safe for 12 months at least."
Still, questions about long-term safety remain. Blackman noted that about half of patients taking tesamorelin developed antibodies to the drug, suggesting an immune reaction, and a few developed a kind of skin rash.
He also wondered if chronic stimulation of the pituitary gland might cause it to enlarge or even become malignant over time -- always a danger in HIV patients, whose immune deficiencies leave them more prone to cancer.
Finally, Blackman noted that a reduction in certain heart risk factors, such as cholesterol or triglyceride levels, isn't the same thing as saying that tesamorelin cut patients' risk of cardiovascular events or death. "It is, in my opinion, the most effective [agent] to date in decreasing abdominal fat, but I think that is all that we can say," he said.
Grinspoon agreed that larger, longer-term study is needed, and he noted that a second phase III trial is already set to begin. "If that one confirms the results of this one, then I am sure [Theratechnologies] will seek approval" from the FDA, he said.
There's more on lipodystrophy at the Foundation for AIDS Research.