Prader-Willi Syndrome Macronutrient Study

NCT02011360 | Completed

• 2 other identifiers: Pro00049226SFR2382
• Study Type: interventional
• Target: 10
• Locations: 2 countries
• Sites: 2

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.

Conditions

Prader Willi Syndrome; Syndromic Obesity; Childhood Obesity

Keywords

Prader Willi syndrome; childhood obesity; ghrelin; appetite regulation

Outcome Measures

Primary Outcomes (1)

• Suppression of ghrelin

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

  10 hour fast following completion of dietary intervention

Secondary Outcomes (2)

• Changes in satiety

  During the 72 hour dietary intervention

• Improvements in insulin sensitivity

  During the 72 hour dietary intervention.

Other Outcomes (1)

• Improvement in inflammatory cytokine profile

  During the 72 hour dietary intervention

Study Arms (2)

Low carbohydrate diet

OTHER

Low carbohydrate diet: 15%carb; 65%fat; 20% protein. This will be administered over 72 hour hospital stay.

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.

Other: Low Carbohydrate diet

Interventions

Low Carbohydrate diet OTHER

Low carbohydrate diet: 15%carb; 65%fat; 20% protein

Low Fat diet

Low Fat diet OTHER

Low Fat diet: 65%carb; 15%fat; 20% protein

Low carbohydrate diet

Eligibility Criteria

• Age: 5 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead
• Foundation for Prader-Willi Research: collaborator

Study Sites (2)

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

University of Alberta

Edmonton, Alberta, T6G 2B7, Canada

Location

Related Publications (23)

• 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.

  PMID: 17636101 BACKGROUND

• 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.

  PMID: 17666087 BACKGROUND

• Haqq 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.

  PMID: 20962018 BACKGROUND

• Haqq 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.

  PMID: 12519848 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

• Haqq 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.

  PMID: 18710462 BACKGROUND

• Newgard 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.

  PMID: 19356713 BACKGROUND

• Laferrere 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.

  PMID: 21525399 BACKGROUND

• Wang 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.

  PMID: 21423183 BACKGROUND

• Sondike 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.

  PMID: 12640371 BACKGROUND

• Foster 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.

  PMID: 12761365 BACKGROUND

• Samaha 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.

  PMID: 12761364 BACKGROUND

• Stern 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.

  PMID: 15148064 BACKGROUND

• Brehm 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.

  PMID: 12679447 BACKGROUND

• Yancy 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.

  PMID: 15148063 BACKGROUND

• Dansinger ML, Gleason JA, Griffith JL, Selker HP, Schaefer EJ. Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction: a randomized trial. JAMA. 2005 Jan 5;293(1):43-53. doi: 10.1001/jama.293.1.43.

  PMID: 15632335 BACKGROUND

• Bistrian BR, Blackburn GL, Stanbury JB. Metabolic aspects of a protein-sparing modified fast in the dietary management of Prader-Willi obesity. N Engl J Med. 1977 Apr 7;296(14):774-9. doi: 10.1056/NEJM197704072961402.

  PMID: 840278 BACKGROUND

• Fields DA, Higgins PB, Radley D. Air-displacement plethysmography: here to stay. Curr Opin Clin Nutr Metab Care. 2005 Nov;8(6):624-9. doi: 10.1097/01.mco.0000171127.44525.07.

  PMID: 16205463 BACKGROUND

• Day N, McKeown N, Wong M, Welch A, Bingham S. Epidemiological assessment of diet: a comparison of a 7-day diary with a food frequency questionnaire using urinary markers of nitrogen, potassium and sodium. Int J Epidemiol. 2001 Apr;30(2):309-17. doi: 10.1093/ije/30.2.309.

  PMID: 11369735 BACKGROUND

• Stubbs RJ, Hughes DA, Johnstone AM, Rowley E, Reid C, Elia M, Stratton R, Delargy H, King N, Blundell JE. The use of visual analogue scales to assess motivation to eat in human subjects: a review of their reliability and validity with an evaluation of new hand-held computerized systems for temporal tracking of appetite ratings. Br J Nutr. 2000 Oct;84(4):405-15. doi: 10.1017/s0007114500001719.

  PMID: 11103211 BACKGROUND

• Liu J, Prudom CE, Nass R, Pezzoli SS, Oliveri MC, Johnson ML, Veldhuis P, Gordon DA, Howard AD, Witcher DR, Geysen HM, Gaylinn BD, Thorner MO. Novel ghrelin assays provide evidence for independent regulation of ghrelin acylation and secretion in healthy young men. J Clin Endocrinol Metab. 2008 May;93(5):1980-7. doi: 10.1210/jc.2007-2235. Epub 2008 Mar 18.

  PMID: 18349056 BACKGROUND

• Haqq AM, Lien LF, Boan J, Arlotto M, Slentz CA, Muehlbauer MJ, Rochon J, Gallup D, McMahon RL, Bain JR, Stevens R, Millington D, Butler MD, Newgard CB, Svetkey LP. The Study of the Effects of Diet on Metabolism and Nutrition (STEDMAN) weight loss project: Rationale and design. Contemp Clin Trials. 2005 Dec;26(6):616-25. doi: 10.1016/j.cct.2005.09.003. Epub 2005 Oct 18.

  PMID: 16239128 BACKGROUND

• Nass R, Liu J, Hellmann P, Coschigano KT, Gaylinn B, Berryman DE, Kopchick JJ, Thorner MO. Chronic changes in peripheral growth hormone levels do not affect ghrelin stomach mRNA expression and serum ghrelin levels in three transgenic mouse models. J Neuroendocrinol. 2004 Aug;16(8):669-75. doi: 10.1111/j.1365-2826.2004.01220.x.

  PMID: 15271059 BACKGROUND

MeSH Terms

Conditions

Prader-Willi Syndrome; Pediatric Obesity

Interventions

Diet, Carbohydrate-Restricted; Diet, Fat-Restricted

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; Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Michael Freemark, MD

  Duke University

  PRINCIPAL INVESTIGATOR

• Andrea M Haqq, MD

  University of Alberta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2013
• First Posted: December 13, 2013
• Study Start: May 1, 2014
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: December 14, 2016

Record last verified: 2016-12

Locations

US (1); CA (1)