ObesityNCT02464514
Macronutrient Regulation of Ghrelin and Peptide YY
A study testing High carbohydrate meal and High fat meal in people with Obesity and Prader Willi Syndrome, run by Duke University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 5 to 17 years
- Conditions the study is for
- Obesity, Prader Willi Syndrome
- What is being tested?
- High carbohydrate meal and High fat meal
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2004to Dec 2005
- 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 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
- Subjects with simple obesity
- Ages 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)
Who cannot join
- 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
- Concomitant use of an investigational drug in the past year
- Patients with an active malignancy
- Parent or legal guardian unable to provide informed consent.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27705
About this study
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
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.
Read the 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.
- Conditions
- Obesity, Prader Willi Syndrome
- Being tested
- High carbohydrate meal, High fat meal
- Keywords
- Obesity, Orexigen, Insulin, Leptin, Adiponectin, Growth hormone replacement
- Medical subject headings
- Obesity, Prader-Willi Syndrome, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High carbohydrate mealOther
65% carbohydrate, 17% protein, and 18% fat
High fat mealOther
58% fat, 17% protein, and 25% carbohydrate
| Study group | Role | What they receive |
|---|---|---|
| Healthy obese children | Other | High carbohydrate meal High fat meal Receives: Other: High carbohydrate meal; Other: High fat meal |
| Children with Prader Willi Syndrome | Other | High carbohydrate meal High fat meal Receives: Other: High carbohydrate meal; Other: High fat meal |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in ghrelin levels
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.
Measured: 4 hours
Change in PYY concentrations
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.
Measured: 4 hours
Secondary outcomes (4)
Fasting Insulin-like growth factor 1 (IGF-1) levels
Baseline Insulin-like growth factor 1 (IGF-1) levels will be measured fasting before the meal in children with PWS, and healthy obese controls
Measured: Baseline
Neuropeptide Y (NPY)
Baseline Neuropeptide Y (NPY) levels will be measured fasting before the meal in children with PWS, and healthy obese controls
Measured: Baseline
Gastric inhibitory polypeptide (GIP)
Baseline Gastric inhibitory polypeptide (GIP) levels will be measured fasting before the meal in children with PWS, and healthy obese controls
Measured: Baseline
Glucagon-like peptide-1 (GLP-1)
Baseline Glucagon-like peptide-1 (GLP-1) levels will be measured fasting before the meal in children with PWS, and healthy obese controls
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2015 (estimated)
- Study startJan 2004
- Primary completionDec 2005
- Study completionDec 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies 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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- 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)
- Responsible party
- Sponsor
- Investigators
- Andrea Haqq, MD, Principal investigator, University of AlbertaMichael Freemark, MD, Study director, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02464514
- Sponsor's protocol ID
- 5028
- Other IDs
- 1K23RR021979
- Status last verified
- Jun 2015
- First submitted
- 1 Jun 2015
- Last updated
- 10 Aug 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Gumus Balikcioglu P, Balikcioglu M, Muehlbauer MJ, Purnell JQ, Broadhurst D, Freemark M, Haqq AM. Macronutrient Regulation of Ghrelin and Peptide YY in Pediatric Obesity and Prader-Willi Syndrome. J Clin Endocrinol Metab. 2015 Oct;100(10):3822-31. doi: 10.1210/jc.2015-2503. Epub 2015 Aug 10.
PubMed 26259133
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02464514
- Acronym / sponsor ID
- 5028
- Conditions
- Obesity, Prader Willi Syndrome
- Keywords
- Obesity, Orexigen, Insulin, Leptin, Adiponectin, Growth hormone replacement
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- 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)
- Study start
- Jan 2004
- Primary completion
- Dec 2005 (actual)
- Study completion
- Dec 2005 (actual)
- First posted
- 8 Jun 2015 (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 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.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Healthy obese children | Other | Other: High carbohydrate meal, Other: High fat mealHigh carbohydrate meal High fat meal |
| Children with Prader Willi Syndrome | Other | Other: High carbohydrate meal, Other: High fat mealHigh carbohydrate meal High fat meal |
Who may qualify
- Ages
- 5 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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
- Subjects with simple obesity
- Ages 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)
Key exclusion criteria (4 listed)
- 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
- Concomitant use of an investigational drug in the past year
- Patients with an active malignancy
- Parent or legal guardian unable to provide informed consent.
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 |
|---|---|---|
| High carbohydrate meal65% carbohydrate, 17% protein, and 18% fat | Other | Children with Prader Willi Syndrome, Healthy obese children |
| High fat meal58% fat, 17% protein, and 25% carbohydrate | Other | Children with Prader Willi Syndrome, Healthy obese children |
Primary outcome
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.
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.
4 secondary outcomes
Fasting Insulin-like growth factor 1 (IGF-1) levels
Time frame: Baseline
Neuropeptide Y (NPY)
Time frame: Baseline
Gastric inhibitory polypeptide (GIP)
Time frame: Baseline
Glucagon-like peptide-1 (GLP-1)
Time frame: Baseline
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 10 Aug 2015.
- Derived from this study: PubMed 26259133Gumus Balikcioglu P, Balikcioglu M, Muehlbauer MJ, Purnell JQ, Broadhurst D, Freemark M, Haqq AM. Macronutrient Regulation of Ghrelin and Peptide YY in Pediatric Obesity and Prader-Willi Syndrome. J Clin Endocrinol Metab. 2015 Oct;100(10):3822-31. doi: 10.1210/jc.2015-2503. Epub 2015 Aug 10.
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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.
Andrea Haqq, MD principal investigator
University of Alberta
Michael Freemark, MD study director
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing High carbohydrate meal and High fat meal in people with Obesity and Prader Willi Syndrome, run by Duke University at 1 site in United States.
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 4 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 10 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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?
Change in ghrelin levels (time frame: 4 hours). The study lists 2 primary outcomes in all. 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 NCT02464514, which also lists 1 linked publication.
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 10 Aug 2015.