Effects of Exenatide on Overweight Adolescents With Prader-Willi Syndrome

NCT01444898 | Completed Results

• 1 other identifier: CCI 11-00227
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Prader-Willi Syndrome

Keywords

Prader-Willi Syndrome; Obesity; Weight; Exenatide; Byetta; Pediatrics; Adolescents

Outcome Measures

Primary Outcomes (9)

• Change in Weight

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

  6 months

• % Change in Body Mass Index (BMI)

  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.

  6 months

• Change in BMI Z-Score

  6 months

• Change in HbA1c (%)

  6 months

• Change in Insulin Levels

  6 months

• Change in Leptin

  6 months

• Change in Acy Ghr

  6 months

• Change in Pancreatic Peptide (PP)

  6 months

• Appetite Scores

  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

  6 months

Study Arms (1)

Exenatide

EXPERIMENTAL

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).

Drug: Exenatide

Interventions

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).

Also known as: Byetta

Exenatide

Eligibility Criteria

• Age: 13 Years - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Children's Hospital Los Angeles: lead

Study Sites (1)

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

Related Publications (10)

• Goldstone AP. The hypothalamus, hormones, and hunger: alterations in human obesity and illness. Prog Brain Res. 2006;153:57-73. doi: 10.1016/S0079-6123(06)53003-1.

  PMID: 16876568 BACKGROUND

• Goldstone AP. Prader-Willi syndrome: advances in genetics, pathophysiology and treatment. Trends Endocrinol Metab. 2004 Jan-Feb;15(1):12-20. doi: 10.1016/j.tem.2003.11.003.

  PMID: 14693421 BACKGROUND

• Suzuki K, Simpson KA, Minnion JS, Shillito JC, Bloom SR. The role of gut hormones and the hypothalamus in appetite regulation. Endocr J. 2010;57(5):359-72. doi: 10.1507/endocrj.k10e-077. Epub 2010 Apr 14.

  PMID: 20424341 BACKGROUND

• Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, Dhillo WS, Ghatei MA, Bloom SR. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab. 2001 Dec;86(12):5992. doi: 10.1210/jcem.86.12.8111.

  PMID: 11739476 BACKGROUND

• Cummings DE, Clement K, Purnell JQ, Vaisse C, Foster KE, Frayo RS, Schwartz MW, Basdevant A, Weigle DS. Elevated plasma ghrelin levels in Prader Willi syndrome. Nat Med. 2002 Jul;8(7):643-4. doi: 10.1038/nm0702-643. No abstract available.

  PMID: 12091883 BACKGROUND

• Paik KH, Jin DK, Song SY, Lee JE, Ko SH, Song SM, Kim JS, Oh YJ, Kim SW, Lee SH, Kim SH, Kwon EK, Choe YH. Correlation between fasting plasma ghrelin levels and age, body mass index (BMI), BMI percentiles, and 24-hour plasma ghrelin profiles in Prader-Willi syndrome. J Clin Endocrinol Metab. 2004 Aug;89(8):3885-9. doi: 10.1210/jc.2003-032137.

  PMID: 15292322 BACKGROUND

• Rosenstock J, Klaff LJ, Schwartz S, Northrup J, Holcombe JH, Wilhelm K, Trautmann M. Effects of exenatide and lifestyle modification on body weight and glucose tolerance in obese subjects with and without pre-diabetes. Diabetes Care. 2010 Jun;33(6):1173-5. doi: 10.2337/dc09-1203. Epub 2010 Mar 23.

  PMID: 20332357 BACKGROUND

• Perez-Tilve D, Gonzalez-Matias L, Alvarez-Crespo M, Leiras R, Tovar S, Dieguez C, Mallo F. Exendin-4 potently decreases ghrelin levels in fasting rats. Diabetes. 2007 Jan;56(1):143-51. doi: 10.2337/db05-0996.

  PMID: 17192476 BACKGROUND

• Seetho IW, Jones G, Thomson GA, Fernando DJ. Treating diabetes mellitus in Prader-Willi syndrome with Exenatide. Diabetes Res Clin Pract. 2011 Apr;92(1):e1-2. doi: 10.1016/j.diabres.2010.12.009. Epub 2011 Jan 11.

  PMID: 21227526 BACKGROUND

• Salehi P, Hsu I, Azen CG, Mittelman SD, Geffner ME, Jeandron D. Effects of exenatide on weight and appetite in overweight adolescents and young adults with Prader-Willi syndrome. Pediatr Obes. 2017 Jun;12(3):221-228. doi: 10.1111/ijpo.12131. Epub 2016 Apr 13.

  PMID: 27071367 RESULT

MeSH Terms

Conditions

Prader-Willi Syndrome; Obesity; Body Weight

Interventions

Exenatide

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Imprinting Disorders; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Limitations and Caveats

* small sample size * referral bias due to small recruitment area * confounding factors during the study, including variations in eating schedule, psychotropic medications, caretaker supervision and activity

Results Point of Contact

• Title: Dr. Mitchell Geffner
• Organization: Children's Hospital Los Angeles

mgeffner@chla.usc.edu

323-361-7032

Study Officials

• Debra Jeandron, MD

  Children's Hospital Los Angeles

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 27, 2011
• First Posted: October 3, 2011
• Study Start: March 1, 2012
• Primary Completion: May 1, 2013
• Study Completion: December 1, 2013
• Last Updated: September 29, 2016
• Results First Posted: September 29, 2016

Record last verified: 2016-09

Locations

US (1)