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

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ClinicalTrials.gov Identifier: NCT04484051
Recruitment Status : Not yet recruiting
First Posted : July 23, 2020
Last Update Posted : July 23, 2020
Sponsor:
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

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.

Condition or disease Intervention/treatment Phase
Prader-Willi Syndrome Drug: Somatropin Drug: Placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Global Growth Hormone Study in Adults With Prader-Willi Syndroom
Estimated Study Start Date : October 1, 2020
Estimated Primary Completion Date : January 1, 2024
Estimated Study Completion Date : January 1, 2024


Arm Intervention/treatment
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.
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)

Placebo Comparator: Placebo comparator: Placebo
Placebo for 12 months.
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.




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Change in fat mass [ Time Frame: 27 months ]
    Change in fat mass (in kg) as measured by Dual Energy X-ray Absorptiometry scan

  2. Change in bone density [ Time Frame: 27 months ]
    Change in bone density (in T-score) as measured by Dual Energy X-ray Absorptiometry scan

  3. 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).

  4. 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)

  5. Change in muscle strength [ Time Frame: 27 months ]
    Change in muscle strength as determined with a handgrip dynamometer

  6. Change in endurance [ Time Frame: 27 months ]
    Change in endurance as estimated with the treadmill stress test

  7. Change in psychosocial functioning [ Time Frame: 27 months ]
    Change in psychosocial functioning as estimated with the Adult Behaviour Checklist


Other Outcome Measures:
  1. Change in weight and waist-hip ratio [ Time Frame: 27 months ]
    Change in weight (in kg) and waist-hip ratio

  2. Change in blood pressure [ Time Frame: 27 months ]
    Change in blood pressure (in mmHg)

  3. Occurence of side-effects [ Time Frame: 27 months ]
    Occurrence of side-effects



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Ages Eligible for Study:   30 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04484051


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

Locations
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Australia
Royal Prince Alfred Hospital
Camperdown, Australia, NSW 2050
Contact: Tania Markovic, MD, PhD    003161419229009    tania.markovic@sydney.edu.au   
Netherlands
Erasmus MC, University Medical Center Rotterdam
Rotterdam, Zuid-Holland, Netherlands, 3015GD
Contact: Laura de Graaff, MD, PhD    0031618843010    l.degraaff@erasmusmc.nl   
Sponsors and Collaborators
Erasmus Medical Center
Pfizer
Foundation for Prader-Willi Research
Prader-Willi Fonds
Investigators
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Principal Investigator: Laura de Graaff, MD, PhD Erasmus MC, University Medical Center Rotterdam
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Responsible Party: dr. Laura C. G. de Graaff-Herder, MD, PhD, Erasmus Medical Center
ClinicalTrials.gov Identifier: NCT04484051    
Other Study ID Numbers: GGAP
First Posted: July 23, 2020    Key Record Dates
Last Update Posted: July 23, 2020
Last Verified: July 2020
Individual Participant Data (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
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.

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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
Keywords provided by dr. Laura C. G. de Graaff-Herder, Erasmus Medical Center:
Prader-Willi syndrome
Growth hormone
Body composition
Cardiovascular disease
Additional relevant MeSH terms:
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Prader-Willi Syndrome
Syndrome
Disease
Pathologic Processes
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Obesity
Overnutrition
Nutrition Disorders