Prader Willi SyndromeNCT02011360
Prader-Willi Syndrome Macronutrient Study
A study testing Low Carbohydrate diet and Low Fat diet in people with Prader Willi Syndrome and Syndromic Obesity, run by Duke University at 2 sites in 2 countries.
Trial summary
The overall objective is to explore the mechanisms by which macronutrients regulate food intake and weight gain in Prader Willi Syndrome (PWS). Previous studies from the investigators' labs suggest that the increased appetite of PWS may be triggered or maintained by an increase in the levels of ghrelin, an… Read more about this study
- Who is it for?
- Ages 5 to 17 years
- Conditions the study is for
- Prader Willi Syndrome, Syndromic Obesity, Childhood Obesity
- What is being tested?
- Low Carbohydrate diet and Low Fat diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 2 sitesin 2 countries
- Study dates
- May 2014to May 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 5 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- diagnosis of Prader Willi syndrome confirmed by chromosome analysis (ie. interstitial deletion of paternally-derived chromosome 15q, uniparental maternal disomy or other chromosome 15 abnormalities)
- age 5 years to 17 years
- written informed consent and assent obtained and willingness to comply with the study schedule and procedures
- free T4, TSH values in the normal range (either endogenous or with thyroxine replacement)
- weight stable (BMI percentile fluctuation of <5 percentiles) over the preceding 2 months prior to the study
Who cannot join
- presence of other clinically significant disease that would impact body composition including diabetes mellitus, chronic inflammatory bowel disease, chronic severe liver or kidney disease or neurologic disorders
- concomitant use of medications known to affect body weight or investigational drug in the past year
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
Duke University Medical Center
Durham, North Carolina, 27705
About this study
Official title: Evidence-Based Approach to Dietary Management of Prader-Willi Syndrome (PWS)
The overall objective is to explore the mechanisms by which macronutrients regulate food intake and weight gain in Prader Willi Syndrome (PWS).
Previous studies from the investigators' labs suggest that the increased appetite of PWS may be triggered or maintained by an increase in the levels of ghrelin, an appetite-stimulating hormone produced primarily by the stomach. This study will compare the effects of low carbohydrate diet versus low fat diet on levels of ghrelin, appetite suppressing hormones and markers of insulin sensitivity in patients with PWS.
The investigators hypothesize that the low carbohydrate diet will suppress plasma active ghrelin and increase appetite-suppressing hormones to a greater degree and for longer duration than the low fat diet and will thereby reduce hyperphagia and increase satiety. The investigators also hypothesize that the low carb diet will improve hormonal and metabolic markers (fatty acids, amino acids and organic acids) of insulin sensitivity and inflammatory cytokine profiles of children with PWS.
- Conditions
- Prader Willi Syndrome, Syndromic Obesity, Childhood Obesity
- Being tested
- Low Carbohydrate diet, Low Fat diet
- Keywords
- Prader Willi syndrome, childhood obesity, ghrelin, appetite regulation
- Medical subject headings
- Prader-Willi Syndrome, Pediatric Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low Carbohydrate dietOther
Low carbohydrate diet: 15%carb; 65%fat; 20% protein
Low Fat dietOther
Low Fat diet: 65%carb; 15%fat; 20% protein
| Study group | Role | What they receive |
|---|---|---|
| Low carbohydrate diet | Other | Low carbohydrate diet: 15%carb; 65%fat; 20% protein. This will be administered over 72 hour hospital stay. Receives: Other: Low Fat diet |
| Low Fat diet | Other | Low fat diet: 65%carb; 15%fat; 20% protein. This will be administered over a 72 hour hospital stay. Receives: Other: Low Carbohydrate diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Suppression of ghrelin
Fasting labs will be obtained immediately following dietary intervention. These labs will include total and active ghrelin.
Measured: 10 hour fast following completion of dietary intervention
Secondary outcomes (2)
Changes in satiety
Changes in subjective hunger will be assessed by an appetite and hyperphagia questionnaire validated for PWS children. This will be completed by the children, with assistance of their parents, at completion of the 72 hour dietary intervention.
Measured: During the 72 hour dietary intervention
Improvements in insulin sensitivity
The analysis will include measurements of adiponectin, GLP-1, glucose, insulin, AST, ALT, insulin sensitivity and a detailed profile ("metabolomics") of amino acids, fatty acids, acylcarnitines, and adipocytokines on the day prior to and immediately following dietary intervention.
Measured: During the 72 hour dietary intervention.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2013 (estimated)
- Study startMay 2014
- Primary completionMay 2016
- Study completionMay 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (23)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 Duke UniversityThe 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
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Foundation for Prader-Willi Research
- Responsible party
- Sponsor
- Investigators
- Michael Freemark, MD, Principal investigator, Duke UniversityAndrea M Haqq, MD, Principal investigator, University of Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02011360
- Sponsor's protocol ID
- Pro00049226
- Other IDs
- SFR2382
- Status last verified
- Dec 2016
- First submitted
- 10 Dec 2013
- Last updated
- 14 Dec 2016
- Results posted
- No
Publications
Dykens EM, Maxwell MA, Pantino E, Kossler R, Roof E. Assessment of hyperphagia in Prader-Willi syndrome. Obesity (Silver Spring). 2007 Jul;15(7):1816-26. doi: 10.1038/oby.2007.216.
PubMed 17636101Haqq AM, Muehlbauer M, Svetkey LP, Newgard CB, Purnell JQ, Grambow SC, Freemark MS. Altered distribution of adiponectin isoforms in children with Prader-Willi syndrome (PWS): association with insulin sensitivity and circulating satiety peptide hormones. Clin Endocrinol (Oxf). 2007 Dec;67(6):944-51. doi: 10.1111/j.1365-2265.2007.02991.x. Epub 2007 Jul 30.
PubMed 17666087Haqq AM, Muehlbauer MJ, Newgard CB, Grambow S, Freemark M. The metabolic phenotype of Prader-Willi syndrome (PWS) in childhood: heightened insulin sensitivity relative to body mass index. J Clin Endocrinol Metab. 2011 Jan;96(1):E225-32. doi: 10.1210/jc.2010-1733. Epub 2010 Oct 20.
PubMed 20962018Haqq AM, Farooqi IS, O'Rahilly S, Stadler DD, Rosenfeld RG, Pratt KL, LaFranchi SH, Purnell JQ. Serum ghrelin levels are inversely correlated with body mass index, age, and insulin concentrations in normal children and are markedly increased in Prader-Willi syndrome. J Clin Endocrinol Metab. 2003 Jan;88(1):174-8. doi: 10.1210/jc.2002-021052.
PubMed 12519848Cummings 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 12091883Haqq AM, Grambow SC, Muehlbauer M, Newgard CB, Svetkey LP, Carrel AL, Yanovski JA, Purnell JQ, Freemark M. Ghrelin concentrations in Prader-Willi syndrome (PWS) infants and children: changes during development. Clin Endocrinol (Oxf). 2008 Dec;69(6):911-20. doi: 10.1111/j.1365-2265.2008.03385.x. Epub 2008 Aug 15.
PubMed 18710462Newgard CB, An J, Bain JR, Muehlbauer MJ, Stevens RD, Lien LF, Haqq AM, Shah SH, Arlotto M, Slentz CA, Rochon J, Gallup D, Ilkayeva O, Wenner BR, Yancy WS Jr, Eisenson H, Musante G, Surwit RS, Millington DS, Butler MD, Svetkey LP. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab. 2009 Apr;9(4):311-26. doi: 10.1016/j.cmet.2009.02.002.
PubMed 19356713Laferrere B, Reilly D, Arias S, Swerdlow N, Gorroochurn P, Bawa B, Bose M, Teixeira J, Stevens RD, Wenner BR, Bain JR, Muehlbauer MJ, Haqq A, Lien L, Shah SH, Svetkey LP, Newgard CB. Differential metabolic impact of gastric bypass surgery versus dietary intervention in obese diabetic subjects despite identical weight loss. Sci Transl Med. 2011 Apr 27;3(80):80re2. doi: 10.1126/scitranslmed.3002043.
PubMed 21525399Wang TJ, Larson MG, Vasan RS, Cheng S, Rhee EP, McCabe E, Lewis GD, Fox CS, Jacques PF, Fernandez C, O'Donnell CJ, Carr SA, Mootha VK, Florez JC, Souza A, Melander O, Clish CB, Gerszten RE. Metabolite profiles and the risk of developing diabetes. Nat Med. 2011 Apr;17(4):448-53. doi: 10.1038/nm.2307. Epub 2011 Mar 20.
PubMed 21423183Sondike SB, Copperman N, Jacobson MS. Effects of a low-carbohydrate diet on weight loss and cardiovascular risk factor in overweight adolescents. J Pediatr. 2003 Mar;142(3):253-8. doi: 10.1067/mpd.2003.4.
PubMed 12640371Foster GD, Wyatt HR, Hill JO, McGuckin BG, Brill C, Mohammed BS, Szapary PO, Rader DJ, Edman JS, Klein S. A randomized trial of a low-carbohydrate diet for obesity. N Engl J Med. 2003 May 22;348(21):2082-90. doi: 10.1056/NEJMoa022207.
PubMed 12761365Samaha FF, Iqbal N, Seshadri P, Chicano KL, Daily DA, McGrory J, Williams T, Williams M, Gracely EJ, Stern L. A low-carbohydrate as compared with a low-fat diet in severe obesity. N Engl J Med. 2003 May 22;348(21):2074-81. doi: 10.1056/NEJMoa022637.
PubMed 12761364Stern L, Iqbal N, Seshadri P, Chicano KL, Daily DA, McGrory J, Williams M, Gracely EJ, Samaha FF. The effects of low-carbohydrate versus conventional weight loss diets in severely obese adults: one-year follow-up of a randomized trial. Ann Intern Med. 2004 May 18;140(10):778-85. doi: 10.7326/0003-4819-140-10-200405180-00007.
PubMed 15148064Brehm BJ, Seeley RJ, Daniels SR, D'Alessio DA. A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. J Clin Endocrinol Metab. 2003 Apr;88(4):1617-23. doi: 10.1210/jc.2002-021480.
PubMed 12679447Yancy WS Jr, Olsen MK, Guyton JR, Bakst RP, Westman EC. A low-carbohydrate, ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia: a randomized, controlled trial. Ann Intern Med. 2004 May 18;140(10):769-77. doi: 10.7326/0003-4819-140-10-200405180-00006.
PubMed 15148063
Study at a glance
From the registry record, last updated by the sponsor on 14 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evidence-Based Approach to Dietary Management of Prader-Willi Syndrome (PWS)
- ClinicalTrials.gov ID
- NCT02011360
- Acronym / sponsor ID
- Pro00049226
- Conditions
- Prader Willi Syndrome, Syndromic Obesity, Childhood Obesity
- Keywords
- Prader Willi syndrome, childhood obesity, ghrelin, appetite regulation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Foundation for Prader-Willi Research
- Study start
- May 2014
- Primary completion
- May 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 13 Dec 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The overall objective is to explore the mechanisms by which macronutrients regulate food intake and weight gain in Prader Willi Syndrome (PWS).
Previous studies from the investigators' labs suggest that the increased appetite of PWS may be triggered or maintained by an increase in the levels of ghrelin, an appetite-stimulating hormone produced primarily by the stomach. This study will compare the effects of low carbohydrate diet versus low fat diet on levels of ghrelin, appetite suppressing hormones and markers of insulin sensitivity in patients with PWS.
The investigators hypothesize that the low carbohydrate diet will suppress plasma active ghrelin and increase appetite-suppressing hormones to a greater degree and for longer duration than the low fat diet and will thereby reduce hyperphagia and increase satiety. The investigators also hypothesize that the low carb diet will improve hormonal and metabolic markers (fatty acids, amino acids and organic acids) of insulin sensitivity and inflammatory cytokine profiles of children with PWS.
Study design
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low carbohydrate diet | Other | Other: Low Fat dietLow carbohydrate diet: 15%carb; 65%fat; 20% protein. This will be administered over 72 hour hospital stay. |
| Low Fat diet | Other | Other: Low Carbohydrate dietLow fat diet: 65%carb; 15%fat; 20% protein. This will be administered over a 72 hour hospital stay. |
Who may qualify
- Ages
- 5 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- diagnosis of Prader Willi syndrome confirmed by chromosome analysis (ie. interstitial deletion of paternally-derived chromosome 15q, uniparental maternal disomy or other chromosome 15 abnormalities)
- age 5 years to 17 years
- written informed consent and assent obtained and willingness to comply with the study schedule and procedures
- free T4, TSH values in the normal range (either endogenous or with thyroxine replacement)
- weight stable (BMI percentile fluctuation of <5 percentiles) over the preceding 2 months prior to the study
Key exclusion criteria (2 listed)
- presence of other clinically significant disease that would impact body composition including diabetes mellitus, chronic inflammatory bowel disease, chronic severe liver or kidney disease or neurologic disorders
- concomitant use of medications known to affect body weight or investigational drug in the past year
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 |
|---|---|---|
| Low Carbohydrate dietLow carbohydrate diet: 15%carb; 65%fat; 20% protein | Other | Low Fat diet |
| Low Fat dietLow Fat diet: 65%carb; 15%fat; 20% protein | Other | Low carbohydrate diet |
Primary outcome
Suppression of ghrelin
Time frame: 10 hour fast following completion of dietary intervention
Fasting labs will be obtained immediately following dietary intervention. These labs will include total and active ghrelin.
2 secondary outcomes
Changes in satiety
Time frame: During the 72 hour dietary intervention
Improvements in insulin sensitivity
Time frame: During the 72 hour dietary intervention.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Dec 2016.
- Background: PubMed 17636101Dykens EM, Maxwell MA, Pantino E, Kossler R, Roof E. Assessment of hyperphagia in Prader-Willi syndrome. Obesity (Silver Spring). 2007 Jul;15(7):1816-26. doi: 10.1038/oby.2007.216.
- Background: PubMed 17666087Haqq AM, Muehlbauer M, Svetkey LP, Newgard CB, Purnell JQ, Grambow SC, Freemark MS. Altered distribution of adiponectin isoforms in children with Prader-Willi syndrome (PWS): association with insulin sensitivity and circulating satiety peptide hormones. Clin Endocrinol (Oxf). 2007 Dec;67(6):944-51. doi: 10.1111/j.1365-2265.2007.02991.x. Epub 2007 Jul 30.
- Background: PubMed 20962018Haqq AM, Muehlbauer MJ, Newgard CB, Grambow S, Freemark M. The metabolic phenotype of Prader-Willi syndrome (PWS) in childhood: heightened insulin sensitivity relative to body mass index. J Clin Endocrinol Metab. 2011 Jan;96(1):E225-32. doi: 10.1210/jc.2010-1733. Epub 2010 Oct 20.
- Background: PubMed 12519848Haqq AM, Farooqi IS, O'Rahilly S, Stadler DD, Rosenfeld RG, Pratt KL, LaFranchi SH, Purnell JQ. Serum ghrelin levels are inversely correlated with body mass index, age, and insulin concentrations in normal children and are markedly increased in Prader-Willi syndrome. J Clin Endocrinol Metab. 2003 Jan;88(1):174-8. doi: 10.1210/jc.2002-021052.
- 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 18710462Haqq AM, Grambow SC, Muehlbauer M, Newgard CB, Svetkey LP, Carrel AL, Yanovski JA, Purnell JQ, Freemark M. Ghrelin concentrations in Prader-Willi syndrome (PWS) infants and children: changes during development. Clin Endocrinol (Oxf). 2008 Dec;69(6):911-20. doi: 10.1111/j.1365-2265.2008.03385.x. Epub 2008 Aug 15.
- Background: PubMed 19356713Newgard CB, An J, Bain JR, Muehlbauer MJ, Stevens RD, Lien LF, Haqq AM, Shah SH, Arlotto M, Slentz CA, Rochon J, Gallup D, Ilkayeva O, Wenner BR, Yancy WS Jr, Eisenson H, Musante G, Surwit RS, Millington DS, Butler MD, Svetkey LP. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab. 2009 Apr;9(4):311-26. doi: 10.1016/j.cmet.2009.02.002.
- Background: PubMed 21525399Laferrere B, Reilly D, Arias S, Swerdlow N, Gorroochurn P, Bawa B, Bose M, Teixeira J, Stevens RD, Wenner BR, Bain JR, Muehlbauer MJ, Haqq A, Lien L, Shah SH, Svetkey LP, Newgard CB. Differential metabolic impact of gastric bypass surgery versus dietary intervention in obese diabetic subjects despite identical weight loss. Sci Transl Med. 2011 Apr 27;3(80):80re2. doi: 10.1126/scitranslmed.3002043.
- Background: PubMed 21423183Wang TJ, Larson MG, Vasan RS, Cheng S, Rhee EP, McCabe E, Lewis GD, Fox CS, Jacques PF, Fernandez C, O'Donnell CJ, Carr SA, Mootha VK, Florez JC, Souza A, Melander O, Clish CB, Gerszten RE. Metabolite profiles and the risk of developing diabetes. Nat Med. 2011 Apr;17(4):448-53. doi: 10.1038/nm.2307. Epub 2011 Mar 20.
- Background: PubMed 12640371Sondike SB, Copperman N, Jacobson MS. Effects of a low-carbohydrate diet on weight loss and cardiovascular risk factor in overweight adolescents. J Pediatr. 2003 Mar;142(3):253-8. doi: 10.1067/mpd.2003.4.
- Background: PubMed 12761365Foster GD, Wyatt HR, Hill JO, McGuckin BG, Brill C, Mohammed BS, Szapary PO, Rader DJ, Edman JS, Klein S. A randomized trial of a low-carbohydrate diet for obesity. N Engl J Med. 2003 May 22;348(21):2082-90. doi: 10.1056/NEJMoa022207.
- Background: PubMed 12761364Samaha FF, Iqbal N, Seshadri P, Chicano KL, Daily DA, McGrory J, Williams T, Williams M, Gracely EJ, Stern L. A low-carbohydrate as compared with a low-fat diet in severe obesity. N Engl J Med. 2003 May 22;348(21):2074-81. doi: 10.1056/NEJMoa022637.
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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.
Michael Freemark, MD principal investigator
Duke University
Andrea M Haqq, MD principal investigator
University of Alberta
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Low Carbohydrate diet and Low Fat diet in people with Prader Willi Syndrome and Syndromic Obesity, run by Duke University at 2 sites in 2 countries.
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 5 inclusion and 2 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 14 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Canada. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Suppression of ghrelin (time frame: 10 hour fast following completion of dietary intervention). 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 NCT02011360, which also lists 23 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 14 Dec 2016; AzTrials last refreshed its copy on 27 Oct 2026.