Clinical trial NCT02011360: Prader-Willi Syndrome Macronutrient Study
Official title: Evidence-Based Approach to Dietary Management of Prader-Willi Syndrome (PWS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Prader Willi Syndrome
Syndromic Obesity
Childhood Obesity
Keywords: Prader Willi syndrome
childhood obesity
ghrelin
appetite regulation
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Foundation for Prader-Willi Research
First posted: 2013-12-13
Enrollment: 10
Sex: ALL
Minimum age (years): 5
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER

Brief 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 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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Suppression of ghrelin
timeFrame: 10 hour fast following completion of dietary intervention
Secondary outcomes:
measure: Changes in satiety
timeFrame: During the 72 hour dietary intervention
measure: Improvements in insulin sensitivity
timeFrame: During the 72 hour dietary intervention.
Other outcomes:
measure: Improvement in inflammatory cytokine profile
timeFrame: During the 72 hour dietary intervention
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
Study officials:
affiliation: Duke University
name: Michael Freemark, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alberta
name: Andrea M Haqq, MD
role: PRINCIPAL_INVESTIGATOR
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citation: Haqq 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.
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