Prader-Willi Syndrome Macronutrient Study

N/ACompletedNCT02011360

Duke University10 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Masking

NONE

Enrollment

Conditions

Prader Willi Syndrome Syndromic Obesity Childhood Obesity

Eligibility

Sex: ALLMin age: 5 YearsMax age: 17 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Suppression of ghrelin

Fasting labs will be obtained immediately following dietary intervention. These labs will include total and active ghrelin.

Time frame: 10 hour fast following completion of dietary intervention

Secondary Outcomes

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.

Time frame: 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.

Time frame: During the 72 hour dietary intervention.