Prader-Willi SyndromeNCT01444898

Effects of Exenatide on Overweight Adolescents With Prader-Willi Syndrome

A study testing Exenatide in people with Prader-Willi Syndrome, run by Children's Hospital Los Angeles at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 13 to 20 years
Conditions the study is for: Prader-Willi Syndrome
What is being tested?: Exenatide
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 10 participants
Where: 1 siteUnited States
Study dates: Mar 2012to Dec 2013
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 13 to 20 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

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

Who cannot join

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

Show all 11Show fewer

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Children's Hospital of Los Angeles
Los Angeles, California, 90027

Other trials in United States

About this study

Official title: 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.

Read the detailed description

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.

Conditions: Prader-Willi Syndrome
Being tested: Exenatide
Keywords: Prader-Willi Syndrome, Obesity, Weight, Exenatide, Byetta, Pediatrics, Adolescents
Medical subject headings: Prader-Willi Syndrome, Obesity, Body Weight

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ExenatideDrug
Also called Byetta
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).

Study groups in NCT01444898
Study group	Role	What they receive
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). Receives: Drug: Exenatide

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Weight
Change in weight (kg) after 6 months of treatment with study drug. Described as mean +/- SD
Measured: 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.
Measured: 6 months
Change in BMI Z-Score
Measured: 6 months
Change in HbA1c (%)
Measured: 6 months
Change in Insulin Levels
Measured: 6 months
Change in Leptin
Measured: 6 months
Change in Acy Ghr
Measured: 6 months
Change in Pancreatic Peptide (PP)
Measured: 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
Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2012Dec 2013

First posted3 Oct 2011 (estimated)
Study startMar 2012
Primary completionMay 2013
Study completionDec 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (10)Papers the sponsor has linked to this study.
Other trials for Prader-Willi SyndromeStudies of the same condition, open and under way.
More trials run by Children's Hospital Los AngelesThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 10 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01444898
Sponsor's protocol ID: CCI 11-00227
Status last verified: Sep 2016
First submitted: 27 Sep 2011
Last updated: 29 Sep 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Undecided

Publications

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.
PubMed 16876568
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.
PubMed 14693421
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.
PubMed 20424341
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.
PubMed 11739476
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.
PubMed 12091883
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.
PubMed 15292322
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.
PubMed 20332357
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.
PubMed 17192476
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.
PubMed 21227526
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.
PubMed 27071367

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 2
A Study of CSTI-500 in Patients With Prader-Willi Syndrome
Prader-Willi Syndrome
Recruiting
Cerebellar TMS and Satiety in Prader-Willi Syndrome
Prader-Willi Syndrome
Enrolling by invitationObservational study
Observational Study of VYKAT™ XR in Patients With Prader-Willi Syndrome
Prader-Willi Syndrome
Active, not recruitingPhase 1/2
A Study of RM-718 in Healthy Subjects and Patients With MC4R Pathway Impairment
Hypothalamic Obesity, Prader-Willi Syndrome
Active, not recruiting
Impact of Bright Light Therapy on Prader-Willi Syndrome
Prader-Willi Syndrome, Excessive Daytime Sleepiness

All Prader-Willi Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 29 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effects of Exenatide on Obesity and Appetite in Overweight Patients With Prader-Willi Syndrome
ClinicalTrials.gov ID: NCT01444898
Acronym / sponsor ID: CCI 11-00227
Conditions: Prader-Willi Syndrome
Keywords: Prader-Willi Syndrome, Obesity, Weight, Exenatide, Byetta, Pediatrics, Adolescents
Study type: Interventional
Recruitment status: Completed
Enrolment: 10 participants (actual)
Lead sponsor: Children's Hospital Los AngelesUniversity, hospital or other
Study start: Mar 2012
Primary completion: May 2013 (actual)
Study completion: Dec 2013 (actual)
First posted: 3 Oct 2011 (estimated)
Results: Posted 29 Sep 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

BACKGROUND:

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.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Exenatide	Experimental	Drug: ExenatideAll 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).

Who may qualify

Ages: 13 to 20 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (11 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ExenatideAlso: ByettaThe 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

Primary outcome

Change in Weight
Time frame: 6 months
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
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
Change in HbA1c (%)
Time frame: 6 months
Change in Insulin Levels
Time frame: 6 months
Change in Leptin
Time frame: 6 months
Change in Acy Ghr
Time frame: 6 months
Change in Pancreatic Peptide (PP)
Time frame: 6 months
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

Results and safety

Results posted to the registry on 29 Sep 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Exenatide	10	9

Primary outcome: Change in Weight

Time frame: 6 months. Mean (Standard Deviation). Unit: kg

Measure	Exenatide n = 10
Value	-.5 (.9)

Exenatide: p = .07, Mixed Models Analysis

Primary outcome: % Change in Body Mass Index (BMI)

Time frame: 6 months. Mean (Standard Deviation). Unit: % change in BMI

Measure	Exenatide n = 10
Value	1.3 (2)

Exenatide: p = 0.08, Mixed Models Analysis

Primary outcome: Change in BMI Z-Score

Time frame: 6 months. Mean (Standard Deviation). Unit: units on a scale

Measure	Exenatide n = 10
Value	.1 (.4)

Exenatide: p = .8, Mixed Models Analysis

Primary outcome: Change in HbA1c (%)

Time frame: 6 months. Mean (Standard Deviation). Unit: percentage

Measure	Exenatide n = 10
Value	-.3 (.2)

Exenatide: p = .04, Mixed Models Analysis

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Exenatide	0 of 10 (0%)	2 of 10 (20%)	Not reported

Limitations and caveats (from the sponsor): * 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

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 16876568Goldstone 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.
Background: PubMed 14693421Goldstone 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.
Background: PubMed 20424341Suzuki 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.
Background: PubMed 11739476Wren 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.
Background: PubMed 12091883Cummings 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.
Background: PubMed 15292322Paik 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.
Background: PubMed 20332357Rosenstock 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.
Background: PubMed 17192476Perez-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.
Background: PubMed 21227526Seetho 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.
Results publication: PubMed 27071367Salehi 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.
Individual participant dataSharing planned: Undecided

Related trials for Prader-Willi Syndrome

RecruitingPhase 2
A Study of CSTI-500 in Patients With Prader-Willi Syndrome
Prader-Willi Syndrome
Recruiting
Cerebellar TMS and Satiety in Prader-Willi Syndrome
Prader-Willi Syndrome
Enrolling by invitationObservational study
Observational Study of VYKAT™ XR in Patients With Prader-Willi Syndrome
Prader-Willi Syndrome
Active, not recruitingPhase 1/2
A Study of RM-718 in Healthy Subjects and Patients With MC4R Pathway Impairment
Hypothalamic Obesity, Prader-Willi Syndrome
Active, not recruiting
Impact of Bright Light Therapy on Prader-Willi Syndrome
Prader-Willi Syndrome, Excessive Daytime Sleepiness

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Debra Jeandron, MD principal investigator

Children's Hospital Los Angeles

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Exenatide in people with Prader-Willi Syndrome, run by Children's Hospital Los Angeles at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Sep 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Weight (time frame: 6 months). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01444898, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2016.