Brain-Derived Neurotrophic Factor in Obesity and Brain Function

NCT01517048 | Completed

• 2 other identifiers: 12005112-CH-0051
• Study Type: observational
• Target: 93
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

Obesity; Genetic Disorder; Mental Retardation; Developmental Delay

Keywords

Body Composition; Obesity; Overweight; Energy Homeostasis; Nociception; Prader-Willi Syndrome; Genetic Disorder; Healthy Volunteer; HV

Outcome Measures

Primary Outcomes (1)

• Serum brain-derived neurotrophic factor concentration

Secondary Outcomes (1)

• Body Composition, Cognitive Function

Eligibility Criteria

• Age: Up to 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%).

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (2)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

University of Alberta

Alberta, Canada

Location

Related Publications (4)

• 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.

  PMID: 20186709 BACKGROUND

• Wisse BE, Schwartz MW. The skinny on neurotrophins. Nat Neurosci. 2003 Jul;6(7):655-6. doi: 10.1038/nn0703-655. No abstract available.

  PMID: 12830151 BACKGROUND

• 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.

  PMID: 12796784 BACKGROUND

• 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.

  PMID: 29718281 DERIVED

MeSH Terms

Conditions

Obesity; Genetic Diseases, Inborn; Intellectual Disability; Learning Disabilities; Overweight; Prader-Willi Syndrome

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Neurodevelopmental Disorders; Mental Disorders; Communication Disorders; Abnormalities, Multiple; Congenital Abnormalities; Chromosome Disorders; Imprinting Disorders

Study Officials

• Jack A Yanovski, M.D.

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2012
• First Posted: January 25, 2012
• Study Start: January 9, 2012
• Study Completion: December 12, 2014
• Last Updated: December 17, 2019

Record last verified: 2014-12-12

Locations

US (1); CA (1)