Esta página foi traduzida automaticamente e a precisão da tradução não é garantida. Por favor, consulte o versão em inglês para um texto fonte.

Brain-Derived Neurotrophic Factor in Obesity and Brain Function

14 de dezembro de 2019 atualizado por: 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.

Visão geral do estudo

Status

Concluído

Condições

Descrição detalhada

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.

Tipo de estudo

Observacional

Inscrição (Real)

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

Canadá
- - Alberta, Canadá
    - University of Alberta
Estados Unidos
- Maryland
  - Bethesda, Maryland, Estados Unidos, 20892
    - National Institutes of Health Clinical Center, 9000 Rockville Pike

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

Não mais velho que 99 anos (Filho, Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Sim

Gêneros Elegíveis para o Estudo

Tudo

Descrição

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:
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
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

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Serum brain-derived neurotrophic factor concentration

Medidas de resultados secundários

Medida de resultado
Body Composition, Cognitive Function

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Publicações e links úteis

A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.

Publicações Gerais

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo

9 de janeiro de 2012

Conclusão do estudo

12 de dezembro de 2014

Datas de inscrição no estudo

Enviado pela primeira vez

24 de janeiro de 2012

Enviado pela primeira vez que atendeu aos critérios de CQ