Dramatic belly-reduction photographs graphically
illustrated the results of the first multicentre,
double-blind, placebo-controlled, randomised, parallel
group phase II/III trial on the effects of recombinant
human growth hormone (GH) on lipohypertrophy that were
presented today by lead investigator, Donald Kotler,
on behalf of Serono - manufacturers of Serostim - in a
late-breaker session at the XIVth International AIDS
Conference in Barcelona.
The STARS trial (Serostim in the Treatment of Adipose
Redistribution Syndrome) or Serono protocol 22388,
found that 4mg GH daily (a 33% reduction in the
currently approved dose for AIDS wasting)
significantly reduced viceral adipose tissue (VAT)
accumulation compared with placebo.
Kotler argued that GH is unique as a therapy for
lipodystrophy because, unlike anabolic steroids, it
preferentially depletes central adipose tissue to a
greater degree than subcutaneous adipose tissue in the
face and extremities. He suggested that 4 mg GH daily
could be considered to be "induction therapy", adding
that more research is ongoing to assess the efficacy
and long-term safety of low dose GH maintainance
therapy in order to sustain its beneficial effects.
As previously reported on aidsmap, two sites in London
are currently recruiting for the HALT study, which
includes low dose (2mg daily) GH amongst its five
treatment arms.
In the STARS trial, 239 people (13% female, 20%
non-caucasian) with symptoms of HARS (HIV-associated
Adipose Redistribution Syndrome) at 23 US sites were
randomised to one of three arms: 4mg GH daily, 4mg GH
and placebo on alternate days, and placebo, by
self-administered subcutaneous injection. Reductions
of VAT were assessed by CT scan, and ratio of trunk to
limb fat assessed by DXA.
At 12 weeks trunk limb fat ratio decreased on both GH
regimes, although only the 4mg daily arm achieved
significant reduction in VAT: 9.2% in males, 13.5% in
females.
Despite total body fat decreases and greater truncal
fat loss greater than 84%, there was no overall weight
loss. Lean Body Mass increased in both GH arms (3kg in
women, 3.5kg in men on GH daily; 2.1kg, 2.8kg,
respectively on GH alternate days).
The most common adverse effects were arthralgia,
peripheral swelling, pain in limbs, parasthesia and
hyperglycemia; fasting and 120 minute glucose rose
signifantly in the GH daily arm, requiring dose
reduction in several patients. In total, 17 (17.1%)
discontinued the trial - 3 on placebo, 4 on GH
alternate days and 10 on GH daily.
Serostim has orphan drug status in the EU, where the
drug is not yet approved for any purpose, unlike the
US where GH was granted accelerated approval for AIDS
wasting in 1998. In a related late-breaker session
Graeme Moyle presented results of a Phase IV trial
using 6mg GH daily for AIDS Wasting, showing that it
was safe and relatively useful after 12 weeks of
treatment. Cost issues, however, will likely mean that
the use of GH for AIDS wasting remains rare, given the
availability of cheaper and equally effective anabolic
steroids.
References
Kotler D et al. Growth Hormone (Serostim) effectively reduces viceral
adipose tissue (VAT) accumulation and non-HDL
cholesterol. XIV International
Conference on AIDS, Barcelona, abstract LbOr18, 2002)
Moyle G et al. Recombinant Human Growth Hormone is effective to treat
HIV/AIDS associated wasting in the era of Highly
Active Anti-Retroviral Therapy. XIV
International Conference on AIDS, Barcelona, abstract LbPeB9012, 2002.