Nordic Study on the Effects of Growth Hormone (Norditropin SimpleXx) Treatment in Adults With Prader-Willi Syndrome

Condition(s) targeted: Prader-Willi Syndrome

Intervention: Norditropin SimpleXx (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: Karolinska University Hospital

Official(s) and/or principal investigator(s):
Charlotte Hoybye, Dr., Principal Investigator, Affiliation: Department of Endocrinology and Diabetology, Karolinska Hospital
Jens S Christiansen, Professor, Study Chair, Affiliation: Århus University Hospital, Denmark

Overall contact:
Charlotte Hoybye, Dr., Phone: +46-8-5177 5379, Email: charlotte.hoybye@karolinska.se

OBJECTIVE(S):

Prader Willi syndrome (PWS) is a multi-symptomatic genetic disorder associated with abnormalities in the growth hormone (GH)-insulin-like-growth factor (IGF)-I axis and in the body composition. GH treatment is a registered indication in children with PWS, and improves growth rate and body composition. One pilot study in adult patients with clinical PWS has shown beneficial effects on body composition without simultaneous significant side effects. The aim of the present study is to evaluate the effects of GH treatment on body composition, muscle function and quality of life in PWS adults.

TRIAL DESIGN:

The study will be an investigator initiated and investigator sponsored multinational and multi-centre trial, including centres in Norway, Sweden and Denmark. Within each centre patients will be randomised (double blind) to one year treatment with daily injections of GH or placebo (efficacy), followed by a two year observation period on GH treatment (safety).

TRIAL POPULATION:

Twenty patients from each centre are included in the study. The patients need a genetically verified diagnosis and should be between 18 and 40 years old. Patients are excluded if GH treatment has been given within the last two years, if they have a malignancy or other serious diseases, in particular severe respiratory diseases.

ASSESSMENTS:

Effect is evaluated primarily as changes in body composition, activity of daily living and quality of life.

SAFETY: Before starting in the study all patients will be examined for tonsillary hypertrophy and sleep apnoea. Oral Glucose Tolerance Tests will be performed regularly.

TRIAL PRODUCT(S):

During the initial 4 weeks of the placebo-controlled study phase patients will be treated with sc injections of GH (Norditropin Simplexx) in the evening with doses of 0. 3 mg/day respectively 0. 4 mg/day if BW is below or above 100 kg. Thereafter doses will be increased to 0. 6 mg/day (0. 8 mg/day) and maintained fixed for 11 months. During the following 24 months open phase doses will be individually titrated.

Official title: Nordic Study on the Effects of Growth Hormone (Norditropin SimpleXx) Treatment in Adults With Prader-Willi Syndrome

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Efficacy Study

Primary outcome:

Changes in body composition (lean body mass and fat mass) measured by dual energy X-ray absorptiometry (DXA)

Muscle and fat mass measured by abdominal and mid-femoral computerized tomography (CT) scan

Activity of daily living measured a.m. Guralnik

Quality of life estimated by questionnaires

Secondary outcome:

Bone mineral density measured by DXA

Effects on forced expiratory volume (Peakflow)

Standard photography appearance according to visual analogue scale (VAS)

Effects on free and total IGF-I, IGF-binding protein (BP)-1 and 3

Effects on lipids (fasting triglycerides(TG), total, HDL and LDL cholesterol)

Effects on body composition measured with bioimpedance

Effects on haemoglobin (Hb), leucocyte and thrombocyte counts, FSH, LH, estradiol, Testosterone, inhibin B, TSH and Thyroxine

Minimum age: 18 Years. Maximum age: 50 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Genetically verified PWS diagnosis (by methylation and FISH test.)

- Between 18 and 50 years old

- Informed consent obtained before any trial-related activities. (Trial-related

activities are any procedure that would not have been performed during normal management of the treatment of the subject.)

Exclusion Criteria:

- Known or suspected allergy to GH preparation.

- Previous participation in this trial.

- GH treatment within the last 1 years

- Malignancy or other serious diseases (ex severe cardiovascular diseases, severe

infections)

- Sexhormone treatment initiated within the last year

- Pregnancy

- Untreated respiratory impairment, untreated sleep apnoea or untreated respiratory

infection.

Charlotte Hoybye, Dr., Phone: +46-8-5177 5379, Email: charlotte.hoybye@karolinska.se

Center for rare Diseases, Department of Pediatrics, Skejby University Hospital, Aarhus N 8200, Denmark; Recruiting
Stense Farholt, Dr., Phone: +45 8949 6709, Email: STF@sks.aaa.dk
Majbrit L Larsen, RN, Phone: +45 8949 6888, Email: MLV@sks.aaa.dk
Stense Farholt, Dr., Sub-Investigator

Endokrinologisk seksjon, Med Avd, Rikshospitalet, Oslo, Norway; Recruiting
Jens Bollerslev, Dr., Phone: +47 2307 1923
Jens Bollerslev, Dr., Sub-Investigator

Department of Endocrinology and Diabetology, Karolinska Hospital, Stockholm 171 76, Sweden; Recruiting
Charlotte Hoybye, Dr., Phone: +46-8-5177 5379, Email: charlotte.hoybye@karolinska.se
Charlotte Hoybye, Dr., Principal Investigator

Starting date: April 2005
Ending date: December 2009
Last updated: September 6, 2006