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Trial record 13 of 395 for:    PYY

Macronutrient Regulation of Ghrelin and Peptide YY

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ClinicalTrials.gov Identifier: NCT02464514
Recruitment Status : Completed
First Posted : June 8, 2015
Last Update Posted : August 10, 2015
Sponsor:
Collaborators:
National Institutes of Health (NIH)
Canadian Institutes of Health Research (CIHR)
Foundation for Prader-Willi Research
Stollery Children's Hospital Foundation
Alberta Diabetes Institute
Sarah W. Stedman Nutrition and Metabolism Center
American Diabetes Association
Duke Children's Miracle Network
National Center for Research Resources (NCRR)
Information provided by (Responsible Party):
Duke University

Brief Summary:
The hyperghrelinemia of children with PWS provides a unique model by which to explore the hormonal and metabolic effects of orexigenic hormones in normal and pathologic conditions. An important question to be addressed by this proposed research includes the macro-nutrient regulation of ghrelin and PYY in obese children and children with PWS. As ghrelin antagonists are considered potential future anti-obesity agents, it is essential to gain understanding of the developmental, nutritional and hormonal regulation of this important orexigenic hormone in children.

Condition or disease Intervention/treatment Phase
Obesity Prader Willi Syndrome Other: High carbohydrate meal Other: High fat meal Not Applicable

Detailed Description:

Obesity continues to be a prevalent health concern affecting every race of the American population. Studies show that obese children are likely to become obese adults. Also, recent studies report significant years of life lost due to the impact of being an obese adult . Thus, insights into the pathogenesis of childhood obesity and preventative measures are needed to combat the inevitable increase in worldwide incidence of obesity and its associated co-morbidities.

Ghrelin is a 28 amino acid acylated peptide which is an endogenous ligand of the growth hormone secretagogue receptor (GHS-R), a hypothalamic G-protein-coupled receptor. Enteroendocrine cells (X/A-like cells) of the stomach are the major site of ghrelin synthesis, although a minor proportion of ghrelin synthesis occurs in other sites such as the hypothalamus, pituitary, duodenum, jejunum and lung. Secreted in response to meals, ghrelin stimulates feeding through activation of anabolic neurons in the hypothalamic arcuate nucleus that co-express neuropeptide Y (NPY) and agouti-related protein (Agrp). Ghrelin relays its information from the GI tract to specific nuclei in the hypothalamus via the gastric afferent vagal nerve.

Studies in rodents support the premise that ghrelin is involved in energy balance. In humans, physiological levels of ghrelin influence energy homeostasis in humans.The rise in plasma ghrelin concentrations during fasting may play a role in meal initiation and body weight regulation.

Nearly all other forms of obesity are associated with low ghrelin levels. Paradoxically, researchers discovered that ghrelin levels in adults and children with PWS are 3-5 times higher than those in age- and BMI-matched controls. Hyperghrelinemia may thus play a causal role in the hyperphagia and obesity of PWS.

The hyperghrelinemia of children with PWS provides a unique model by which to explore the hormonal and metabolic effects of orexigenic hormones in normal and pathologic condtions. An important question to be addressed by this proposed research includes the macro-nutrient regulation of ghrelin in normal children and children with PWS. As ghrelin antagonists are considered potential future anti-obesity agents, it is essential to gain understanding of the developmental, nutritional and hormonal regulation of this important orexigenic hormone in children.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Investigation of the Developmental, Nutritional and Hormonal Regulation of Ghrelin in Children With Prader-Willi Syndrome (PWS) and Children With Hypothalamic-Derived Obesity: Macronutrient Regulation Sub-study
Study Start Date : January 2004
Actual Primary Completion Date : December 2005
Actual Study Completion Date : December 2005

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Healthy obese children
High carbohydrate meal High fat meal
Other: High carbohydrate meal
65% carbohydrate, 17% protein, and 18% fat

Other: High fat meal
58% fat, 17% protein, and 25% carbohydrate

Children with Prader Willi Syndrome
High carbohydrate meal High fat meal
Other: High carbohydrate meal
65% carbohydrate, 17% protein, and 18% fat

Other: High fat meal
58% fat, 17% protein, and 25% carbohydrate




Primary Outcome Measures :
  1. Change in ghrelin levels [ Time Frame: 4 hours ]
    The change in ghrelin levels will be measured before and after meal consumption in children with PWS, and healthy obese controls. Following an overnight 8 hour fast, subjects will be given either a high carbohydrate or high fat meal. Subjects will be allowed 25 minutes to consume everything on their food tray. Blood samples will be obtained before the meal (fasting) and every 30 minutes thereafter for 4 hours.

  2. Change in PYY concentrations [ Time Frame: 4 hours ]
    The change in PYY concentration levels will be measured before and after meal consumption in children with PWS, and healthy obese controls. Following an overnight 8 hour fast, subjects will be given either a high carbohydrate or high fat meal. Subjects will be allowed 25 minutes to consume everything on their food tray. Blood samples will be obtained before the meal (fasting) and every 30 minutes thereafter for 4 hours.


Secondary Outcome Measures :
  1. Fasting Insulin-like growth factor 1 (IGF-1) levels [ Time Frame: Baseline ]
    Baseline Insulin-like growth factor 1 (IGF-1) levels will be measured fasting before the meal in children with PWS, and healthy obese controls

  2. Neuropeptide Y (NPY) [ Time Frame: Baseline ]
    Baseline Neuropeptide Y (NPY) levels will be measured fasting before the meal in children with PWS, and healthy obese controls

  3. Gastric inhibitory polypeptide (GIP) [ Time Frame: Baseline ]
    Baseline Gastric inhibitory polypeptide (GIP) levels will be measured fasting before the meal in children with PWS, and healthy obese controls

  4. Glucagon-like peptide-1 (GLP-1) [ Time Frame: Baseline ]
    Baseline Glucagon-like peptide-1 (GLP-1) levels will be measured fasting before the meal in children with PWS, and healthy obese controls



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Ages Eligible for Study:   5 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of PWS confirmed by chromosome analysis (i.e. interstitial deletion of paternally-derived chromosome 15Q, uniparental maternal disomy or other chromosome 15 abnormalities) or normal control
  2. Subjects with simple obesity
  3. Ages 5 years to 17 years
  4. Written informed consent and assent obtained and willingness to comply with the study schedule and procedures.
  5. Free T4, TSH values in the normal range (either endogenous or with thyroxine replacement)

Exclusion Criteria:

  1. Patients with any other clinically significant disease that would have an impact on body composition including diabetes mellitus, chronic inflammatory bowel disease, chronic severe liver or kidney disease or neurologic disorders
  2. Concomitant use of an investigational drug in the past year
  3. Patients with an active malignancy
  4. Parent or legal guardian unable to provide informed consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02464514


Locations
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United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27705
Sponsors and Collaborators
Duke University
National Institutes of Health (NIH)
Canadian Institutes of Health Research (CIHR)
Foundation for Prader-Willi Research
Stollery Children's Hospital Foundation
Alberta Diabetes Institute
Sarah W. Stedman Nutrition and Metabolism Center
American Diabetes Association
Duke Children's Miracle Network
National Center for Research Resources (NCRR)
Investigators
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Principal Investigator: Andrea Haqq, MD University of Alberta
Study Director: Michael Freemark, MD Duke University

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT02464514     History of Changes
Other Study ID Numbers: 5028
1K23RR021979 ( U.S. NIH Grant/Contract )
First Posted: June 8, 2015    Key Record Dates
Last Update Posted: August 10, 2015
Last Verified: June 2015

Keywords provided by Duke University:
Obesity
Orexigen
Insulin
Leptin
Adiponectin
Growth hormone replacement

Additional relevant MeSH terms:
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Syndrome
Obesity
Prader-Willi Syndrome
Disease
Pathologic Processes
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Nutrients
Growth Substances
Physiological Effects of Drugs