Brain-Derived Neurotrophic Factor in Obesity and Brain Function
2019년 12월 14일 업데이트: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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.
연구 개요
상세 설명
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.
연구 유형
관찰
등록 (실제)
93
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
99년 이하 (어린이, 성인, 고령자)
건강한 자원 봉사자를 받아들입니다
예
연구 대상 성별
모두
설명
- INCLUSION CRITERIA:
Subject Inclusion Criteria:
- 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.
- 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.
- 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:
For all subjects:
- Pregnancy
- 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
- If age >12 months, greater than 2% body weight loss in preceding 6 months
- Anorexiant or weight loss medication use in preceding 6 months
For control subjects:
- Chronic medical conditions anticipated to affect results or impede study participation
- Medication use will be reviewed on a case-by-case basis by the Principal Investigator to determine eligibility
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
|---|
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Serum brain-derived neurotrophic factor concentration
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2차 결과 측정
결과 측정 |
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Body Composition, Cognitive Function
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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
일반 간행물
- Han JC, Reyes-Capo DP, Liu CY, Reynolds JC, Turkbey E, Turkbey IB, Bryant J, Marshall JD, Naggert JK, Gahl WA, Yanovski JA, Gunay-Aygun M. Comprehensive Endocrine-Metabolic Evaluation of Patients With Alstrom Syndrome Compared With BMI-Matched Controls. J Clin Endocrinol Metab. 2018 Jul 1;103(7):2707-2719. doi: 10.1210/jc.2018-00496.
- Cohen-Cory S, Kidane AH, Shirkey NJ, Marshak S. Brain-derived neurotrophic factor and the development of structural neuronal connectivity. Dev Neurobiol. 2010 Apr;70(5):271-88. doi: 10.1002/dneu.20774.
- Wisse BE, Schwartz MW. The skinny on neurotrophins. Nat Neurosci. 2003 Jul;6(7):655-6. doi: 10.1038/nn0703-655. No abstract available.
- Xu B, Goulding EH, Zang K, Cepoi D, Cone RD, Jones KR, Tecott LH, Reichardt LF. Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor. Nat Neurosci. 2003 Jul;6(7):736-42. doi: 10.1038/nn1073.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작
2012년 1월 9일
연구 완료
2014년 12월 12일
연구 등록 날짜
최초 제출
2012년 1월 24일
QC 기준을 충족하는 최초 제출
2012년 1월 24일
처음 게시됨 (추정)
2012년 1월 25일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2019년 12월 17일
QC 기준을 충족하는 마지막 업데이트 제출
2019년 12월 14일
마지막으로 확인됨
2014년 12월 12일
추가 정보
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