Fat Metabolism and Melanocortin 3 Receptors in African Americans

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Collaborator:
National Institute of Minority Healthy and Health Disparities
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )
ClinicalTrials.gov Identifier:
NCT01851421
First received: May 9, 2013
Last updated: June 20, 2014
Last verified: January 2014
  Purpose

Background:

- Melanocortin receptors are proteins in the body that help send messages between body systems. One such receptor, the melanocortin 3 receptor (MC3R), is important for regulating body weight. Differences in MC3R can affect fat metabolism - or how the body handles fat. Some people who have changes in the MC3R genetic code are heavier than those who do not have these changes. These changes are found more often in African Americans. Researchers want to study the MC3R in African American adults to see how these changes may affect fat metabolism. They will look at overweight adults with either the most common genetic code for the MC3R or a rare variant.

Objectives:

- To study the role of the MC3R in body weight and fat metabolism.

Eligibility:

  • Healthy African American volunteers between 18 and 55 years of age.
  • Volunteers must be overweight (body mass index at least 30 kg/m2) but weigh less than 450 lbs.

Design:

  • The study consists of an outpatient screening visit and a 7-day inpatient visit with dietary studies.
  • Participants will be screened with a physical exam and medical history. Blood samples will be collected. (Participants will need to fast for 10 hours before giving blood samples.) A body scan will be given to determine fat, bone, and muscle content. Participants will complete a 3-day dietary assessment to record their food and drink consumption. They will also have an exercise test to look at heart and lung function.
  • Participants will have a 7-day inpatient stay. They will have a regular diet for the first 3 days of the study. For the final 4 days, they will have a diet with a higher fat content.
  • During the inpatient visit, participants will have the following study procedures:
  • Body measurements
  • Daily exercise routine
  • Imaging studies of the body
  • Measurement of a whole day s energy expenditure (spending one day in metabolic chamber-day 5)
  • Frequent blood samples
  • Urine collection for 24 hours (days 3 and 7)
  • Fat biopsy (collection of a small sample of fat tissue from under the skin on the abdomen)
  • Insulin and metabolism tests while eating the two different diets (day 4 and day 7).
  • After the final insulin and metabolism test, participants will be discharged from the study.

Condition
Obesity
Healthy Volunteers

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Fat Metabolism and Function Altering Polymorphisms in MC3R

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Free fatty acid reflux rate measured on a high- fat diet during the hyperinsulinemic state. [ Time Frame: ongoing ] [ Designated as safety issue: No ]

Estimated Enrollment: 400
Study Start Date: March 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Detailed Description:

Our prior studies have found that children with homozygosity for two rare Melanocortin 3 Receptor (MC3R) polymorphisms (T6K+V81I) have greater fat mass compared to wild type children. These polymorphisms are about 10-fold more prevalent in Non-Hispanic Black than White Americans. In vitro, T6K+V81I causes MC3R hypofunction. Since mouse models and limited human data suggest the MC3R may be involved in regulating substrate oxidation, and therefore fatty acid disposal, we propose to study 30 Non-Hispanic Black BMI-matched subjects with homozygous T6K+V81I or wild-type MC3R to compare substrate turnover (fatty acids and glucose) during fasting and under conditions of hyperinsulinemia after adaptation from a normal-fat to a high-fat isocaloric diet. Using adipocytes obtained from biopsies, we will also study glucose and fatty acid uptake, storage and mobilization in vitro. We hypothesize that this study will shed light on the role of the MC3R in substrate metabolism and energy expenditure, and will yield information that may assist in the development of more effective approaches for the treatment of obesity in Non-Hispanic Black Americans.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA

Volunteers will qualify if they meet the following criteria

  1. Age 18-55 years. Subject age is limited to 55y maximum because subjects are required to complete a maximal exercise test as part of their evaluations. Studying only younger patients decreases the risks of such exercise tests.
  2. Non-Hispanic Black by self-identification with (to the best of the subject s knowledge) all 4 grandparents considered Non-Hispanic Black. Because T6K+V81I MC3R is 10-times more prevalent among Non-Hispanic Blacks, only Non-Hispanic Blacks will be eligible to participate.
  3. Obesity, defined as body mass index (BMI) (Bullet)30 kg/m2 and weight under 450 lbs, in order for subjects to be able to undergo DXA scanning.
  4. Willing to undergo genetic screening to establish that subject is either homozygous wild type for MC3R or homozygous for T6K+V81I MC3R, with the absence of other genetic causes of monogenic obesity (for both study and control groups).
  5. Good general health. In general, subjects should take no medications. However, individuals taking medications for obesity-related co-morbid conditions, who have not had changes in dosage for more than 6 months, may be included, at the discretion of the principal investigator.
  6. For females, a negative pregnancy test at the initial evaluation. Because pregnancy is a state in which weight gain is expected and appropriate, pregnant individuals would not be suitable for this study. Sexually active women must be using an effective form of birth control. These methods include abstinence, oral contraceptives, an intrauterine device (IUD), levonogestrol implants (Norplant), or medroxyprogesterone acetate injections (Depo-provera shots). If one of these cannot be used, contraceptive foam with a condom is recommended (One of these methods must have been used by the subject for at least two months prior to the start of the study).

EXCLUSION CRITERIA

Volunteers will be excluded (and referred to non-experimental treatment programs as needed) for the following reasons:

  1. Subjects with a major medical illnesses that in the opinion of the medical team would impede interpretation of results, including significant renal, hepatic (other than obesity-related steatosis), gastrointestinal, most endocrinologic (e.g., Cushing syndrome, untreated hyper- or hypothyroidism, pheochromocytoma), hematological problems or pulmonary disorders; or porphyria;
  2. Current users of tobacco products;
  3. Subjects following a diet with specific food requirements such as vegetarian, vegan, or kosher;
  4. Women who are pregnant or who are currently nursing an infant or have irregular menses;
  5. Individuals who have current substance abuse or a psychiatric disorder or other condition that in the opinion of the investigators would impede competence or adherence;
  6. Recent (3 months) use of anorexiant medications;
  7. Subjects using medications known to affect glucose and fatty acid metabolism and/or absorption; h) Subjects with weight change of more than 3% of body weight in the past two months;

i) Subjects currently using a weight loss diet;

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01851421

Contacts
Contact: Andrew P Demidowich, M.D. (301) 594-1176 demidowicha@mail.nih.gov
Contact: Jack A Yanovski, M.D. (301) 496-0858 jy15i@nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
National Institute of Minority Healthy and Health Disparities
Investigators
Principal Investigator: Jack A Yanovski, M.D. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )
ClinicalTrials.gov Identifier: NCT01851421     History of Changes
Other Study ID Numbers: 130097, 13-CH-0097
Study First Received: May 9, 2013
Last Updated: June 20, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Body Fat
Adult
Obesity
Free Fatty Acids
Melanocortin-3 Receptor

Additional relevant MeSH terms:
Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms

ClinicalTrials.gov processed this record on August 19, 2014