Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

Effects of Exenatide on Overweight Adolescents With Prader-Willi Syndrome

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Mitchell E. Geffner, Children's Hospital Los Angeles
ClinicalTrials.gov Identifier:
NCT01444898
First received: September 27, 2011
Last updated: September 27, 2016
Last verified: September 2016

September 27, 2011
September 27, 2016
March 2012
May 2013   (final data collection date for primary outcome measure)
  • Change in Weight [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Change in weight (kg) after 6 months of treatment with study drug. Described as mean +/- SD
  • % Change in Body Mass Index (BMI) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.
  • Change in BMI Z-Score [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Change in HbA1c (%) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Change in Insulin Levels [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Change in Leptin [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Change in Acy Ghr [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Change in Pancreatic Peptide (PP) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Appetite Scores [ Time Frame: 6 months ] [ Designated as safety issue: No ]

    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

  • Change in weight [ Time Frame: Weight at baseline, 1 month, 3 months and 6 months of treatment ] [ Designated as safety issue: No ]
  • Change in Body Mass Index (BMI) [ Time Frame: BMI at baseline, 1 month, 3 months and 6 months of treatment ] [ Designated as safety issue: No ]
  • Change in body composition [ Time Frame: Body composition at baseline and 6 months of treatment ] [ Designated as safety issue: No ]
    The investigators will measure body fat composition by whole body DEXA scan at baseline and after 6 months of treatment with exenatide.
  • Change in appetite [ Time Frame: Appetite scored at baseline, 1 month, 3 months and 6 months of treatment ] [ Designated as safety issue: No ]
    The investigators will measure appetite scores using a syndrome-validated hyperphagia questionnaire administered at all visits except for the screening visit.
Complete list of historical versions of study NCT01444898 on ClinicalTrials.gov Archive Site
Not Provided
Change in fasting and post-prandial levels of obesity-related hormones [ Time Frame: Levels will be measured at baseline, 1 month, 3 months, and 6 months of treatment. ] [ Designated as safety issue: No ]
The investigators will measure serum fasting and post-prandial levels of obesity-realated hormones (ghrelin, PYY, PP, leptin, glucose, and insulin) over a 6-month course of exenatide. The investigators will measure fasting and post-prandial serum/plasma levels of these analytes during a standardized mixed meal tolerance test prior to and then after 6 months of treatment. The investigators will also monitor fasting levels of these analytes after 1 and 3 months of treatment
Not Provided
Not Provided
 
Effects of Exenatide on Overweight Adolescents With Prader-Willi Syndrome
Effects of Exenatide on Obesity and Appetite in Overweight Patients 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.

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.

Interventional
Not Provided
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Prader-Willi Syndrome
Drug: Exenatide
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 Name: Byetta
Experimental: Exenatide
All subjects enrolled in this study will be given Exenatide for 6 months. Exenatide: 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).
Intervention: Drug: Exenatide

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
10
December 2013
May 2013   (final data collection date for primary outcome measure)

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
Both
13 Years to 20 Years   (Child, Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01444898
CCI 11-00227
No
Undecided
Not Provided
Mitchell E. Geffner, Children's Hospital Los Angeles
Children's Hospital Los Angeles
Not Provided
Principal Investigator: Debra Jeandron, MD Children's Hospital Los Angeles
Children's Hospital Los Angeles
September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP