Brain-Derived Neurotrophic Factor in Obesity and Brain Function
| Status: | Completed |
|---|---|
| Conditions: | Obesity Weight Loss, Women's Studies |
| Therapuetic Areas: | Endocrinology, Reproductive |
| Healthy: | No |
| Age Range: | Any - 99 |
| Updated: | 3/20/2019 |
| Start Date: | January 9, 2012 |
| End Date: | December 12, 2014 |
Brain-Derived Neurotrophic Factor in Obesity and Neurocognitive Function
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.
- 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.
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.
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.
- 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
We found this trial at
2
sites
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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