Growth Hormone Study in Adults With Prader-Willi Syndrome (GAP)

Growth Hormone Study in Adults With Prader-Willi Syndroom

The overall objective of this study is to measure the effect of growth hormone (GH) treatment on physical and psychosocial health in adults with Prader-Willi syndrome. Adults with PWS who have not been treated with GH during the past three years and who will start with GH treatment as part of regular patient care will be asked for informed consent to participate in this open-label prospective cohort study. We hypothesize that growth hormone treatment will improve the physical and psychosocial health.

Study Overview

• Status: Not yet recruiting
• Conditions: Prader-Willi Syndrome
• Intervention / Treatment: Drug: Somatropin; Drug: Placebo

Detailed Description

OBJECTIVES:

To measure the effect of GHt on physical and psychosocial health in adults with PWS.

The primary endpoint is change in lean body mass (LBM (kg)) as assessed by Dual Energy X-ray Absorptiometry (DEXA) scan. Secondary endpoints are total fat mass, bone density, physical health and psychosocial health. Also the occurrence of side-effects will be assessed. Only data that are collected as part of regular patient care will be used.

STUDY DESIGN:

Open-label prospective cohort study.

STUDY POPULATION:

Adults with PWS who have not been treated with GH during the past three years and who will start with GHt as part of regular patient care.

• Study Type: Observational
• Enrollment (Anticipated): 25
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Trui van Essen, MD; Phone Number: 0031658869674; Email: g.vanessen@erasmusmc.nl

Study Locations

• Netherlands
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3015GD
      • Erasmus MC, University Medical Center Rotterdam

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adults with PWS who have not been treated with GH during the past three years and who will start with GHt as part of regular patient care.

Description

Inclusion Criteria:

• The patient is diagnosed with Prader-Willi syndrome (genetically confirmed)

Exclusion Criteria:

• Non cooperative behaviour
• Pregnancy
• Known malignancies
• Poorly controlled diabetes (HbA1c > 64 mmol/mol (8%))
• Untreated obstructive sleep apnea (apnea-hypopnea index > 5)
• Body mass index above 40 kg/m2
• Upper-airway obstruction of any cause

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Routine clinical care with Genotropin treatment; Data collection throughout routine clinical care with subcutaneous injections Genotropin, 0.6-0.8 mg/day. Participants start with 0.2 mg/day and the dose increases with 0.2 mg/day per month to a maximum dose of 0.6-0.8 mg/day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in lean body mass	Change in lean body mass (in kg) as measured by Dual Energy X-ray Absorptiometry scan	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in fat mass	Change in fat mass (in kg) as measured by Dual Energy X-ray Absorptiometry scan	36 months
Change in bone density	Change in bone density (in T-score) as measured by Dual Energy X-ray Absorptiometry scan	36 months
Change in physical strength	Change in physical strenght as measured by handgrip dynamometer and sit-to-stand tests	36 months
Change in laboratory measurements	Changes in the following laboratory measurements: Glycosylated hemoglobin (mmol/mol); Total cholesterol (mmol/L); Low-density lipoprotein cholesterol (mmol/L); High-density lipoprotein cholesterol (mmol/L); Insulin-like growth factor 1 (nmol/L); Free thyroxine 4 (pmol/L); Luteinizing hormone (U/I); Follicle stimulating hormone (U/I); Estradiol or testosterone (nmol/L); Sex hormone binding globulin (nmol/L); Aspartate transaminase (U/L); Alanine transaminase (U/L); Alkaline phosphatase (U/L); Gamma glutamyl transpeptidase (U/L); Total bilirubin (micromol/L); Lactate dehydrogenase (U/L); Urea (mmol/L); Creatinine (micromol/L); Hemoglobin (mmol/L); Hematocrit (L/L); Mean corpuscular volume (fL); Leukocytes (10^9/L); Thrombocytes (10^9/L); 25-OH vitamin D (nmol/L)	36 months
Change in psychosocial functioning	Change in psychosocial functioning as estimated with the Adult Behaviour Checklist	36 months
Change in caregiver burden	Change in caregiver burden as estimated with the Zarit Burden Interview	36 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in weight and waist-hip ratio	Change in weight (in kg) and waist-hip ratio	36 months
Change in blood pressure	Change in blood pressure (in mmHg)	36 months
Occurence of side-effects	Occurrence of side-effects	36 months

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Collaborators: Foundation for Prader-Willi Research; Prader-Willi Fonds

Study record dates

Study Major Dates

• Study Start (Anticipated): March 24, 2023
• Primary Completion (Anticipated): September 1, 2026
• Study Completion (Anticipated): October 1, 2026

Study Registration Dates

• First Submitted: July 15, 2020
• First Submitted That Met QC Criteria: July 21, 2020
• First Posted (Actual): July 23, 2020

Study Record Updates

• Last Update Posted (Estimate): February 16, 2023
• Last Update Submitted That Met QC Criteria: February 15, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Cardiovascular disease; Body composition; Prader-Willi syndrome; Growth hormone
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Overnutrition; Nutrition Disorders; Genetic Diseases, Inborn; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Obesity; Syndrome; Prader-Willi Syndrome
• Other Study ID Numbers: GAP (Other Identifier: Baylor)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The individual participant data has not been finalized yet. The investigators intent to share the full anonymized dataset, study protocol and statistical analysis plan upon request after publication of the results. Informed consent forms will not be shared.
• IPD Sharing Time Frame: The data will become available around begin 2027 (after publication of the results). The data will be available for 15 years.
• IPD Sharing Access Criteria: Upon reasonable request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No