| Conditions: |
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Obesity - Genetic Disorder - Mental Retardation - Developmental Delay |
| Purpose: |
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Background:
- Prader-Willi syndrome (PWS) and MC4R genetic mutations are two conditions that can cause
problems with appetite regulation. People with PWS often have behavior and thinking
problems. People with MC4R mutations may have problems with attention. These problems may be
related to Brain-Derived Neurotrophic Factor (BDNF), a protein that is important for brain
development. Researchers want to study people with PWS and MC4R mutations to see how BDNF is
involved in these conditions. Specifically, body weight and brain function will be studied,
and compared with healthy volunteers.
Objectives:
- To study how BDNF affects body weight and brain function in people with PWS and MC4R
mutations.
Eligibility:
- Individuals of any age who have Prader-Willi syndrome or MC4R genetic mutations.
- Healthy volunteers of any age to act as control participants.
Design:
- Participants will be screened with a medical history and physical exam. Height, weight,
and waist/hip circumferences will be measured. Blood samples will be taken for genetic
and other tests.
- Participants will fill out questionnaires about eating habits, pain perception, and
sleep behavior.
- Participants will keep a 3-day food diary to record all food and drinks eaten.
- Tests and questionnaires will be given to study thinking, speech, movement, behavior,
and mood. Some tests will be done on a computer; other tests will be on paper. Tests
may also involve performing tasks with blocks and other objects.
- Participants may have other tests as directed. These will include hot and cold
sensitivity tests, imaging studies like x-rays, and measurements of body fat and water
content.
- Treatment will not be provided as part of this study.
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| Study Summary: |
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Brain-derived neurotrophic factor (BDNF) is a protein that is important in nervous system
development and function. BDNF also appears to function downstream of the
leptin-melanocortin signaling pathway to control appetite. In both animals and humans,
diminished BDNF function is associated with hyperphagia, obesity, and neurocognitive
deficits. We propose to study BDNF in two hyperphagic disorders: Prader-Willi syndrome and
MC4R function-altering mutations. We hypothesize that patients with PWS may have increased
BDNF during infancy, followed by a decline in BDNF that precedes the onset of hyperphagia
and persists after the onset of obesity. We hypothesize that patients with MC4R mutations
will have decreased BDNF, the severity of which will be associated with the degree of MC4R
functional loss caused by the specific mutation(s) in each individual. To test these
hypotheses, we wish to conduct cross-sectional studies to evaluate serum BDNF
concentrations, metabolism, body composition, and neurocognition in: subjects with PWS,
subjects with MC4R mutations and control subjects matched for age, sex, race, and BMI. If
alterations in BDNF are found to be associated with PWS and/or MC4R mutations, these
investigations could lead to future studies of BDNF receptor agonists as mechanism-specific
pharmacologic therapy for hyperphagia and obesity in PWS and MC4R mutations, or BDNF
receptor antagonists for failure-to-thrive in neonatal PWS.
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| Criteria: |
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- INCLUSION CRITERIA:
Subject Inclusion Criteria:
1. For PWS subjects: We will enroll 75 subjects of all ages who have diagnosis of PWS
confirmed by chromosome analysis (i.e. interstitial deletion of paternally-derived
chromosome 15q, uniparental maternal disomy or other chromosome 15 abnormalities).
Our goal is to have 25 infants, 25 non-obese, and 25 obese subjects in order to
assess the different phases associated with PWS. Subjects receiving growth hormone
therapy may enroll if the dose has been stable for the preceding 6 months.
2. For MC4R subjects: We will screen up to 200 subjects for mutations of MC4R and enroll
50 subjects of all ages who have diagnosis of homozygous or heterozygous MC4R
mutation confirmed by sequencing of the MC4R gene. Both functional-altering (N=25)
and non-pathologic (N=25) mutations will be included.
3. For control subjects: We will enroll 125 subjects of all ages who match with PWS or
MC4R subjects by age (plus-minus 10%), sex, race, and BMI percentile (plus-minus10%).
EXCLUSION CRITERIA:
Subject Exclusion Criteria:
1. For all subjects:
1. Pregnancy
2. Individuals who have, or whose parent or guardians have, current substance abuse
or a psychiatric disorder or other condition which, in the opinion of the
investigators, would impede competence or compliance or possibly hinder
completion of the study
3. If age > 12 months, greater than 2% body weight loss in preceding 6 months
4. Anorexiant or weight loss medication use in preceding 6 months
2. For control subjects:
1. Chronic medical conditions anticipated to affect results or impede study
participation
2. Medication use will be reviewed on a case-by-case basis by the Principal
Investigator to determine eligibility
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| NCT ID: |
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NCT01517048 |
| Primary Contact: |
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Principal Investigator
Joan C Han, M.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Melanie D Hicks
Phone: (301) 402-6762
Email: hicksmd@mail.nih.gov
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| Backup Contact: |
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Email: hanjo@mail.nih.gov
Joan C Han, M.D.
Phone: (301) 435-7820
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| Location Contact: |
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Bethesda, Maryland 20892
United States
For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)
Phone: 800-411-1222
Email: prpl@mail.cc.nih.gov
Site Status: Recruiting |