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NCT Number: NCT01444898

Effects of Exenatide on Overweight Adolescents With Prader-Willi Syndrome

Prader-Willi Syndrome (PWS) is one of the most common genetic causes of obesity. Obesity is a major source of morbidity and mortality in this population. It can lead to sleep apnea, cor pulmonale, diabetes mellitus, and atherosclerosis. PWS has distinct characteristics that set it apart from other forms of obesity including insatiable appetite and food-seeking behavior which can be disruptive to home and school activities, and can cause severe social and psychological turmoil within families. PWS is also associated with unique hormonal abnormalities, most notably hyperghrelinemia. Ghrelin is a gut hormone produced in the stomach that stimulates food intake during a fast. It is hypothesized that the extremely high ghrelin levels in patients with PWS may cause or contribute to their insatiable appetite. Exenatide, a medication used in the treatment of type 2 diabetes mellitus in adults, appears to suppress ghrelin levels and cause weight loss. It was designed to mimic glucagon-like peptide 1 (GLP-1), an incretin hormone that stimulates insulin secretion and delays gastric emptying, among other effects. In the present study, the investigators will investigate the effects of a 6 month trial of exenatide in overweight adolescents with PWS. The investigators will quantify the changes in weight and body composition, as well as subjective measures of appetite, and concentrations of appetite-associated hormones. The investigators hypothesize that exenatide will improve weight, body composition, appetite, and plasma ghrelin levels during the treatment period.

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Key information

Conditions

Prader-Willi Syndrome Abnormalities, Multiple Body Weight Chromosome Disorders Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Imprinting Disorders Intellectual Disability Nervous System Diseases Neurobehavioral Manifestations Neurologic Manifestations Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

13 year–20 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

About this study

BACKGROUND:

Prader-Willi syndrome (PWS) is associated with hyperphagia and hyperghrelinemia with major morbidity because of obesity without effective medical treatment targeting hyperphagia. Exenatide (Byetta [synthetic Exendin-4]; AstraZeneca, Wilmington DE) is a GLP-1 receptor agonist which reduces appetite and weight and may be an effective treatment in PWS.

OBJECTIVE: The objective of this study is to determine the effect of a 6-month trial of exenatide on appetite, weight and gut hormones in youth with PWS.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Diagnosis of Prader Willi Syndrome confirmed by genetic testing (DNA methylation or FISH)
  • Ages 13-20 years
  • body mass index (BMI) > 85th percentile for age and gender

Exclusion criteria

  • Is currently using or has previously used a glucagon-like peptide-1 (GLP-1) agonist
  • History of pancreatitis, or renal failure
  • History of familial pancreatitis
  • Amylase, or lipase levels > 2.5 times the upper limit of normal any time in the previous 2 years
  • Creatinine clearance < 30 mL/min
  • Other syndromic diagnoses
  • gastrointestinal (GI) or renal illness in the 1 month prior to entering study
  • Inability to take study drug
  • Pregnancy
  • Initiation of growth hormone (GH), estrogen, or testosterone or change > 25% of dose/kg/day during the 6 months prior to starting study
  • Non-English speaking

Treatment and study plan

exenatide

Drug

The investigators will give patients naive to GLP-1 agonists exenatide per manufacturer dosing recommendations for 6 months. The investigators will begin by giving 5 mcg subcutaneously twice a day for 1 month and then increase the dose to 10 mcg subcutaneously twice a day for the remainder of the study (5 months).

Other names: Byetta

Primary outcomes

  1. Change in Weight

    Time frame: 6 months

    Change in weight (kg) after 6 months of treatment with study drug. Described as mean +/- SD

  2. % Change in Body Mass Index (BMI)

    Time frame: 6 months

    Prior to analysis, distributions were evaluated for normality and natural log transformation was performed to analyse data not normally distributed. Data are presented as mean ±SD unless not normally distributed, in which case they are presented as median with intra-quartile ranges (25th and 75th percentiles). Within-subject changes between visits were analysed by mixed model repeated measures. When the overall F-test for difference among visits was significant, Dunnett-adjusted pairwise comparisons were made between baseline and each subsequent visit.

  3. Change in BMI Z-Score

    Time frame: 6 months

  4. Change in HbA1c (%)

    Time frame: 6 months

  5. Change in Insulin Levels

    Time frame: 6 months

  6. Change in Leptin

    Time frame: 6 months

  7. Change in Acy Ghr

    Time frame: 6 months

  8. Change in Pancreatic Peptide (PP)

    Time frame: 6 months

  9. Appetite Scores

    Time frame: 6 months

    Appetite scores using a syndrome-validated hyperphagia questionnaire

    11 item questionnaire divided into subcategories of behavior (5 questions), drive (4 questions), severity (2 questions). Tallied and analyzed as total and subcategory scores. Each question scored 1-5 with higher scores correlating with worse hyperphagia.

    Possible ranges: Total 11-55, behavior 5-25, drive 4-20, severity 2-10

Sponsors and collaborators

Lead sponsor

Children's Hospital Los Angeles

Other

Registry information

Official study title

Effects of Exenatide on Obesity and Appetite in Overweight Patients With Prader-Willi Syndrome

Important dates

Study start
2012
Primary completion
2013
Study completion
2013
First posted
Oct 3, 2011
Registry last updated
Sep 29, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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