ObesityNCT01517048
Brain-Derived Neurotrophic Factor in Obesity and Brain Function
An observational study of Obesity and Genetic Disorder, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- Obesity, Genetic Disorder, Mental Retardation
- How many people
- 93 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 9 Jan 2012to 12 Dec 2014
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 99 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- 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%).
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: 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.
Read more
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.
Read the detailed description
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.
- Conditions
- Obesity, Genetic Disorder, Mental Retardation, Developmental Delay
- Keywords
- Body Composition, Obesity, Overweight, Energy Homeostasis, Nociception, Prader-Willi Syndrome, Genetic Disorder, Healthy Volunteer, HV
- Medical subject headings
- Obesity, Genetic Diseases, Inborn, Intellectual Disability, Learning Disabilities, Overweight, Prader-Willi Syndrome
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum brain-derived neurotrophic factor concentration
Secondary outcomes (1)
Body Composition, Cognitive Function
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2012 (estimated)
- Study start9 Jan 2012
- Study completion12 Dec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 93 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Jack A Yanovski, M.D., Principal investigator, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01517048
- Sponsor's protocol ID
- 120051
- Other IDs
- 12-CH-0051
- Status last verified
- 12 Dec 2014
- First submitted
- 24 Jan 2012
- Last updated
- 17 Dec 2019
- Results posted
- No
Publications
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.
PubMed 20186709Wisse BE, Schwartz MW. The skinny on neurotrophins. Nat Neurosci. 2003 Jul;6(7):655-6. doi: 10.1038/nn0703-655. No abstract available.
PubMed 12830151Xu 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.
PubMed 12796784Han 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.
PubMed 29718281
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Brain-Derived Neurotrophic Factor in Obesity and Neurocognitive Function
- ClinicalTrials.gov ID
- NCT01517048
- Acronym / sponsor ID
- 120051
- Conditions
- Obesity, Genetic Disorder, Mental Retardation, Developmental Delay
- Keywords
- Body Composition, Obesity, Overweight, Energy Homeostasis, Nociception, Prader-Willi Syndrome, Genetic Disorder, Healthy Volunteer
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 93 participants (actual)
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- 9 Jan 2012
- Study completion
- 12 Dec 2014
- First posted
- 25 Jan 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- Up to 99 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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%).
Key exclusion criteria (9 listed)
- For all subjects:
- For control subjects:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Serum brain-derived neurotrophic factor concentration
1 secondary outcome
Body Composition, Cognitive Function
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
- Background: PubMed 20186709Cohen-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.
- Background: PubMed 12830151Wisse BE, Schwartz MW. The skinny on neurotrophins. Nat Neurosci. 2003 Jul;6(7):655-6. doi: 10.1038/nn0703-655. No abstract available.
- Background: PubMed 12796784Xu 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.
- Derived from this study: PubMed 29718281Han 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jack A Yanovski, M.D. principal investigator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Obesity and Genetic Disorder, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum brain-derived neurotrophic factor concentration. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01517048, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2019; AzTrials last refreshed its copy on 27 Oct 2026.