Effects of growth hormone treatment after final height in Prader-Willi Syndrome: A double-blind multicenter, cross-over study on the effects of growth hormone versus placebo on body composition and psychosocial behaviour in transition

GH improves height velocity, and body composition in PWS children. Preliminary
data also suggest improvement of psychosocial functioning during GH. When
epiphysial fusion is complete and final height is reached, GH-treatment has to
be discontinued. However, discontinuation of GH results in a decrease of lean
body mass, an increase of body fat percentage and a deterioration of
psychosocial behaviour. A preliminary study showed that also young adults with
PWS might benefit from GH-treatment, with regard to body composition, and
psychosocial wellbeing. Adults and adolescents with PWS often develop
psychiatric disorders, how these psychiatric disorders develop is unknown.

to evaluate the effects of GH versus withdrawal of GH, after final height is
reached, on weight, body composition, psychosocial functioning, carbohydrate
metabolism, circulating lipids, and respiratory function during transition
period until the age of 24. Describe the development of psychiatric disorders
in adolescents with PWS.

After stratification for BMI, gender, originally followed in the GH study vs.
otherwise GH-treated patients, subjects will be randomized to either placebo or
GH-treatment group, according to a double blind, placebo-controlled cross-over
design during the first 2 years. After 2 years, all patients receive GH
treatment after ATT-GHRH test has been performed. Anthropometric assessments
and blood pressure will be performed every 3 months. Six-monthly, assessment of
body composition (DXA), carbohydrate metabolism and circulating lipids and
other laboratory parameters will be performed. Yearly, evaluation of
sleep-related breathing (polysomnography), cognition and behaviour (GIT, TVZ)
will be performed and a psychiatric investigation will be done.

Treatment with GH: Genotropin 0.67 mg/m2/day s.c. or placebo.
Psychiatric investigation.

Invasive: Patients will be treated with GH and placebo by daily subcutaneous
injecties. It has been shown that these injections are usually very well
tolerated. Venapuncture will be performed every 6 months, which is necessary
for monitoring during GH treatment

Non-invasive: Diet and exercise are part of the regular management of PWS.
Three-monthly, a general physical examination will be performed, which is not
painfull and will take approximately 15 minutes. Two times a year a DEXA
measurement will be performed. Subjects are lying down as the measurement is
performed. They are accompanied by one parent. Radiation dose is very low. Once
a year, GIT will be performed, which requires the patient to concentrate.
Behaviour is assessed by parent questionnaires, and therefore will not be a
burden to the patients.
Every year, a polysomnography will be performed in the sleep center. Patients
will be accompanied by one parent. Several electrodes will be placed on the
face, limbs and thorax. Polysomnography is recommended for all subjects with
PWS, irrespective of GH treatment. Yearly psychiatric evaluation that wil take
3 hours