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Increasing growth hormone release reduces
abdominal fat accumulation and improves lipid levels in HIV-infected
patients
BOSTON - December 5, 2007 - Treatment with an investigational
drug that induces the release of growth hormone significantly improved
the symptoms of HIV lipodystrophy, a condition involving the redistribution
of fat and other metabolic changes in patients receiving combination
drug therapy for HIV infection. A team led by researchers from Massachusetts
General Hospital (MGH) and McGill
University Health Centre found that treatment with tesamorelin,
a growth-hormone-releasing factor, significantly reduced deep abdominal
fat deposits and improved the metabolic aspects of HIV lipodystrophy
in a group of patients with the syndrome. The report of a six-month
Phase 3 clinical trial of tesamorelin appears in the December 6
New England Journal of Medicine.
"This appears to be the most promising strategy to date for
a safe, effective method of reducing excess visceral fat deposits
and improving lipid abnormalities in HIV-infected patients, thereby
improving their risk for cardiovascular disease," says Steven
Grinspoon, MD, of the MGH
Neuroendocrine Unit and Program in Nutritional Metabolism, the
report's senior and corresponding author.
A significant number of HIV-infected individuals who receive antiviral
therapy develop lipodystrophy. Symptoms of the syndrome include
a loss of subcutaneous fat in the face, arms, and legs and increased
fat deposits in the abdomen. The metabolic aspects of the syndrome
- changes in cholesterol and other blood lipids, and development
of insulin resistance - could increase the risk of cardiovascular
disease in HIV-infected patients.
Earlier studies found that growth hormone secretion is reduced in
men with lipodystrophy. Since directly injecting growth hormone
can have significant side effects, researchers at the MGH previously
investigated the use of growth-hormone-releasing hormone (GHRH)
to increase levels in a way that mimics natural control of hormone
levels. In a
2004 study, they showed that patients receiving GHRH injections
appeared to have more normal growth hormone levels and improvements
in fat distribution.
The current study followed up an earlier Phase 2 study of tesamorelin,
a growth-hormone-releasing factor that can be dosed only once a
day instead of twice. Study participants - HIV lipodystrophy patients
recruited from 43 sites around the U.S. and Canada - were randomly
assigned to receive either tesamorelin or a placebo, self administered
daily for six months. At the end of the study period, researchers
measured participants' visceral fat - deposits around organs deep
in the abdomen - and subcutaneous fat in arms and legs. They also
recorded key lipid measurements and levels of the hormone IGF-1,
which reflects the release of growth hormone. In addition, participants
were surveyed at the beginning and end of the study on their perceptions
of their bodies and any distress they felt.
Among the more than 325 participants who completed the study, those
receiving tesamorelin had significant reductions in abdominal fat,
measured by CT scan, resulting in a 20 percent difference from those
in the placebo group. Lipid measurements - including triglycerides,
total cholesterol, HDL, and the ratio of total cholesterol to HDL
- also improved significantly; IGF-1 levels reflected increased
release of growth hormone in the tesamorelin group. Participants
receiving the drug also reported significant improvements in their
body image and reduced levels of distress.
"Longer-term studies are necessary to confirm our results,
and another confirmatory Phase 3 trial needs to be completed to
comply with FDA requirements," says Grinspoon. "But this
study shows clearly that the novel strategy of inducing the release
of endogenous growth hormone can improve symptoms of lipodystrophy,
relieving patient distress - which may improve their compliance
with therapy - and reducing several cardiovascular risk factors."
Grinspoon is a professor of Medicine at Harvard Medical School.
The study was supported by Theratechnologies, a biopharmaceutical
company based in Montréal that is developing tesamorelin,
and the data were analyzed by Quintiles, Canada. Julian Falutz,
MD, of McGill University Health Center, is the first author. Additional
co-authors are Soraya Allas, MD, PhD, Koenraad Blot, MD, and Diane
Potvin, MSc, Theratechnologies; Donald Kotler, MD, Columbia College
of Physicians and Surgeons; Michael Somero, MD, Palm Springs, Calif.;
Daniel Berger, MD, Northstar Health Care, Chicago; Stephen Brown,
MD, AIDS Research Alliance, Los Angeles; Gary Richmond, MD, Ft.
Lauderdale, Fla.; Jeffrey Fessel, Kaiser Foundation Research Institute,
San Francisco; and Ralph Turner, MD, PhD, Phase V Techologies, Wellesley,
Mass.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of more than $500 million
and major research centers in AIDS, cardiovascular research, cancer,
computational and integrative biology, cutaneous biology, human
genetics, medical imaging, neurodegenerative disorders, regenerative
medicine, systems biology, transplantation biology and photomedicine.
Media Contacts: Sue
McGreevey, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
Information about Clinical Trials
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