HGH Therapy for Adult Growth Hormone
Deficiency (GHD)
Two multicenter, double-blind, placebo-controlled clinical trials were conducted
using Nutropin HGH (rDNA origin) for injection in GH-deficient adults.
One study was conducted in subjects with adult-onset GHD, mean age 48.3 years,
n=166, at doses of 0.0125 or 0.00625 mg/kg/day; doses of 0.025 mg/kg/day
were not tolerated in these subjects.
A second study was conducted in previously treated subjects with childhood-onset
GHD, mean age 23.8 years, n=64, at randomly assigned doses of 0.025 or 0.0125
mg/kg/day.
The studies were designed to assess the effects of replacement therapy with
GH on body composition. Significant changes from baseline to Month 12 of
treatment in body composition (i.e., total body % fat mass, trunk % fat mass,
and total body % lean mass by DEXA scan) were seen in all Nutropin HGH groups
in both studies (p<0.0001 for change from baseline and vs. placebo), whereas
no statistically significant changes were seen in either of the placebo groups.
In the adult-onset study, the Nutropin HGH group improved mean total body
fat from 35.0% to 31.5%, mean trunk fat from 33.9% to 29.5%, and mean lean
body mass from 62.2% to 65.7%, whereas the placebo group had mean changes
of 0.2% or less (p=not significant).
Due to the possible effect of GH-induced fluid retention on DEXA measurements
of lean body mass, DEXA scans were repeated approximately 3 weeks after
completion of therapy; mean % lean body mass in the Nutropin HGH group was
65.0%, a change of 2.8% from baseline, compared with a change of 0.4% in
the placebo group (p<0.0001 between groups).
In the childhood-onset study, the high-dose Nutropin HGH group improved mean
total body fat from 38.4% to 32.1%, mean trunk fat from 36.7% to 29.0%, and
mean lean body mass from 59.1% to 65.5%; the low-dose Nutropin HGH group
improved mean total body fat from 37.1% to 31.3%, mean trunk fat from 37.9%
to 30.6%, and mean lean body mass from 60.0% to 66.0%; the placebo group
had mean changes of 0.6% or less (p=not significant).
In the adult-onset study, significant decreases from baseline to Month 12
in LDL cholesterol and LDL:HDL ratio were seen in the Nutropin HGH group
compared to the placebo group, p<0.02; there were no statistically significant
between-group differences in change from baseline to Month 12 in total
cholesterol, HDL cholesterol, or triglycerides.
In the childhood-onset study, significant decreases from baseline to Month
12 in total cholesterol, LDL cholesterol, and LDL:HDL ratio were seen in
the high-dose Nutropin HGH group only, compared to the placebo group,
p<0.05. There were no statistically significant between-group differences
in HDL cholesterol or triglycerides from baseline to Month 12. In the
childhood-onset study, 55% of the patients had decreased spine bone mineral
density (BMD) (z-score<-1) at baseline.
The administration of Nutropin HGH (n=16) (0.025 mg/kg/day) for two years
resulted in increased spine BMD from baseline when compared to placebo (n=13)
(4.6% vs. 1.0%, respectively, p<0.03); a transient decrease in spine BMD
was seen at six months in the Nutropin HGH -treated patients.
Thirty-five percent of subjects treated with this dose had supraphysiological
levels of IGF-I at some point during the study, which may carry unknown risks.
No significant improvement in total body BMD was found when compared to placebo.
A lower GH dose (0.0125 mg/kg/day) did not show significant increments in
either of these bone parameters when compared to placebo.
No statistically significant effects on BMD were seen in the adult-onset
study where patients received GH (0.0125 mg/kg/day) for one year.
Muscle strength, physical endurance, and quality of life measurements were
not markedly abnormal at baseline, and no statistically significant effects
of Nutropin HGH therapy were observed in the two studies. |