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

• ClinicalTrials.gov Identifier: NCT04484051
• Recruitment Status: Not yet recruiting
• First Posted: July 23, 2020
• Last Update Posted: July 23, 2020
• Sponsor: Erasmus Medical Center
• Collaborators: Pfizer; Foundation for Prader-Willi Research; Prader-Willi Fonds
• Information provided by (Responsible Party): dr. Laura C. G. de Graaff-Herder, Erasmus Medical Center

Tracking Information

• First Submitted Date: July 15, 2020
• First Posted Date: July 23, 2020
• Last Update Posted Date: July 23, 2020
• Estimated Study Start Date: October 1, 2020
• Estimated Primary Completion Date: January 1, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 21, 2020)

Change in lean body mass [ Time Frame: 27 months ]

Change in lean body mass (in kg) as measured by Dual Energy X-ray Absorptiometry scan

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: July 21, 2020)

• Change in fat mass [ Time Frame: 27 months ]
  Change in fat mass (in kg) as measured by Dual Energy X-ray Absorptiometry scan
• Change in bone density [ Time Frame: 27 months ]
  Change in bone density (in T-score) as measured by Dual Energy X-ray Absorptiometry scan
• Change in cardiovascular fitness [ Time Frame: 27 months ]
  Change in cardiovascular fitness as estimated with an ECG during the treadmill stress test. We look for axis devations in LEAD I and aVF. We also look for signs of ischemia (ST depression, T wave inversion and pathologic Q waves).
• Change in laboratory measurements [ Time Frame: 27 months ]
  Changes in the following laboratory measurements:

  • Fasting blood glucose (mmol/L)
  • Glycosylated hemoglobin (mmol/mol)
  • Total cholesterol (mmol/L)
  • Low-density lipoprotein cholesterol (mmol/L)
  • High-density lipoprotein cholesterol (mmol/L)
  • Triglycerides (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)
• Change in muscle strength [ Time Frame: 27 months ]
  Change in muscle strength as determined with a handgrip dynamometer
• Change in endurance [ Time Frame: 27 months ]
  Change in endurance as estimated with the treadmill stress test
• Change in psychosocial functioning [ Time Frame: 27 months ]
  Change in psychosocial functioning as estimated with the Adult Behaviour Checklist

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: July 21, 2020)

• Change in weight and waist-hip ratio [ Time Frame: 27 months ]
  Change in weight (in kg) and waist-hip ratio
• Change in blood pressure [ Time Frame: 27 months ]
  Change in blood pressure (in mmHg)
• Occurence of side-effects [ Time Frame: 27 months ]
  Occurrence of side-effects

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Global Growth Hormone Study in Adults With Prader-Willi Syndrome
• Official Title: Global Growth Hormone Study in Adults With Prader-Willi Syndroom
• Brief Summary: The overall objective of this study is to measure the effect of growth hormone treatment on physical and psychosocial health in adults of 30 years or older with Prader-Willi syndrome. Patients are randomized to placebo or growth hormone treatment during the first year. They will switch treatment during the second year, so that each participant receives one year of growth hormone treatment and one year of placebo (cross-over study). We hypothesize that growth hormone treatment will improve the physical and psychosocial health.

Detailed Description

OBJECTIVES:

The overall objective is to measure the effect of growth hormone treatment (GHt) on physical and psychosocial health in adults of 30 years or older with Prader-Willi syndrome (PWS).

The primary objective is to measure the effect of GHt on lean body mass as measured by Dual Energy X-ray Absorptiometry scan in adults of 30 years or older with PWS.

The secondary objective is to measure the effect of GHt on total fat mass, bone density, physical health cardiovascular fitness, laboratory measurements, muscle strength, endurance, and psychosocial functioning in adults of 30 years or older with PWS. Also the occurrence of side-effects will be assessed.

STUDY DESIGN:

Randomized, double-blinded, placebo controlled crossover trial for two years with a washout period of 3 months.

STUDY POPULATION:

50 adults with PWS of 30 years or older who have not been treated with GH during the past three years.

INTERVENTION:

subcutaneous injections of growth hormone (Genotropin, 5.0 mg/mL) in a dosage of 0.6 - 0.8 mg/day. The comparator is placebo.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Prader-Willi Syndrome

Intervention

• Drug: Somatropin
  The intervention is growth hormone treatment (Genotropin), 0.6 - 0.8 mg/day subcutaneous for one year. It is an intramural medicament with an add-on. Participants start with 0.2 mg/day. The growth hormone dose increases with 0.2 mg/day per month to a maximum dose of 0.6 - 0.8 mg/day based on clinical signs (occurrence of side-effects)
  Other Name: Genotropin (5,0 mg/mL)
• Drug: Placebo
  The comparator is placebo, 0.6 - 0.8 mg/day subcutaneous for one year. Participants start with 0.2 mg/day. The dose increases with 0.2 mg/day per month to a maximum dose of 0.6 - 0.8 mg/day.

Study Arms

• Active Comparator: Active comparator: Genotropin
  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.
  Intervention: Drug: Somatropin
• Placebo Comparator: Placebo comparator: Placebo
  Placebo for 12 months.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: July 21, 2020): 50
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 1, 2024
• Estimated Primary Completion Date: January 1, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• The patient is diagnosed with Prader-Willi syndrome (genetically confirmed)
• The patient is 30 years or older
• In case of previous GH treatment (for example in trial setting), GH should be stopped at least three years before starting the study
• The patient is treated by a dietitian (caloric restriction) for at least three months

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
• Change in testosterone or estrogen replacement therapy in the last three months prior to study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 30 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Laura de Graaff, MD, PhD; 0031618843010; l.degraaff@erasmusmc.nl

• Listed Location Countries: Australia, Netherlands

Administrative Information

• NCT Number: NCT04484051
• Other Study ID Numbers: GGAP
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: The data will become available around july 2024 (after publication of the results). The data will be available for 15 years.
• Access Criteria: Upon reasonable request.

• Current Responsible Party: dr. Laura C. G. de Graaff-Herder, Erasmus Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Erasmus Medical Center
• Original Study Sponsor: Same as current

Collaborators

• Pfizer
• Foundation for Prader-Willi Research
• Prader-Willi Fonds

Investigators

• Principal Investigator: Laura de Graaff, MD, PhD; Erasmus MC, University Medical Center Rotterdam

• PRS Account: Erasmus Medical Center
• Verification Date: July 2020