Human Growth Hormone Reverses Wasting in Clinical Trial

A multicenter placebo-controlled trial with 178 volunteers
has shown clear evidence that human growth hormone can
reverse wasting syndrome, which causes many deaths in cases
of advanced AIDS. It is the first treatment for wasting which
has been proven to consistently restore lean body mass,
according to principal investigator Morris Schambelan, M.D.,
an endocrinologist at San Francisco General Hospital. The
data was analyzed immediately before the Yokohama conference
and first reported at that meeting. The results were not
surprising, because there have been positive anecdotal
reports from patients and physicians involved in the trial.

To be eligible for the Serono study, patients had to have
lost at least 10 percent of their pre-illness weight, or to
weigh less than 90 percent of their ideal body weight; those
in the trial had lost an average of 14 percent. Since the
hormone could not work if people did not eat, study
volunteers had to be able to eat at least 75 percent of their
estimated caloric requirement. Exercise may also be helpful,
but the study did not prescribe it, due to the difficulty of
designing an exercise program suitable for a scientific
study; participants were not discouraged from exercising,
however.

In the trial, 90 volunteers received growth hormone (an
average dose of 6 mg per day -- 0.1 mg per kilogram --
administered subcutaneously each day) and 88 received placebo
for three months; after that time, all were given "open
label" access to the drug, and some have been on it for up to
two years, providing additional information about long-term
safety.

During the trial, patients in the placebo group initially
gained an average of one pound, but lost most of this again
during the three months. Those in the growth-hormone group
gained an average of more than three and a half pounds, and
have sustained or increased this gain afterwards; several
patients eventually gained more than 20 pounds while on
extended treatment.

More interesting was an average gain in lean body mass of
more than six pounds during the trial. Since this is more
than the weight gain, it means that participants lost an
average of about three pounds of fat. In this study, lean
body mass was measured by a high-tech system called DEXA
(dual energy X-ray absorptiometry), which is generally used
for measurement of bone density, but has been adapted for
measurement of body composition. However, a much simpler
system known as bioelectrical impedance has been shown to be
comparable to DEXA.

There were five deaths among the 178 volunteers during or
shortly after the three-month trial; three were receiving the
hormone and two were on placebo. These deaths were due to
infections in persons with very low T-helper counts. (The
average T-helper count of the persons in the trial was 84,
with half of them being below 50.)

Human Growth Hormone -- Background

Human growth hormone is a prescription drug which has been
approved in the U.S. for several years for treating growth-
hormone deficiency in children; it is currently sold by
Genentech Inc. (trade name Protropin) and by Eli Lilly and
Company (trade name Humatrope). The recent trial, however,
was sponsored by a different company, Serono Laboratories
Inc., which has its own human growth hormone which is now
approved in 50 countries but not in the U.S., due to
exclusivity provisions of the Orphan Drug Act; that
exclusivity ran out in March 1994, and the company is now
seeking FDA approval for treating children with growth-
hormone deficiency, in addition to investigating the drug's
efficacy in the wasting syndrome.

There are slight biological differences between the versions
of human growth hormone sold by the different companies, with
the Serono product being derived from mammalian cells, and
the others from bacteria. There is no evidence that the
products act differently in people, however.

When used to treat wasting syndrome, human growth hormone
seems to work by a direct effect on protein metabolism, not
necessarily by correcting a growth-hormone deficiency.

Since human growth hormone can cause various side effects, it
must be used cautiously.

Unfortunately, human growth hormone is very expensive.
Increasing competition may reduce the price somewhat, but it
will still remain an expensive drug. With the new study,
there is now a strong case for its medical necessity in some
AIDS patients; this should make reimbursement easier. (An
earlier study was published in 1993 (1); this should
strengthen the case for reimbursement.)

Serono is now sponsoring another large controlled trial, with
180 patients, one third of whom are receiving placebo. This
trial will focus on additional safety data, to satisfy the
FDA. Once the product is approved specifically for AIDS
wasting, reimbursement should be automatic.

Nutrition for HIV-Associated Wasting -- Brochure Available

Serono Laboratories is producing an educational brochure of
nutrition information for persons with wasting syndrome; it
is useful regardless of whether human growth hormone or any
other treatment is used. The text appeared in the June 1994
issue of BETA (Bulletin of Experimental Treatments for AIDS)
published by the San Francisco AIDS Foundation. For a free
copy, call Gina Cella at Serono, 800/283-8088 ext. 5251, or
write to her attention at: Serono Laboratories, Inc., 100
Longwater Circle, Norwell, MA 02061.

References

1. Mulligan K, Grunfeld C, Hellerstein MK, Neese RA, and
Schambelan M. Anabolic effects of recombinant human growth
hormone in patients with wasting associated with human
immunodeficiency virus infection. JOURNAL OF CLINICAL
ENDOCRINOLOGY AND METABOLISM. 1993; volume 77, number 4,
pages 956-962.