ObesityNCT01851421
Fat Metabolism and Melanocortin 3 Receptors in African Americans
An observational study of Obesity and Healthy Volunteers, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Obesity, Healthy Volunteers
- How many people
- 88 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Sep 2013to 28 Jun 2021
- 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 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: Comunity sample
Who may be able to join
- Volunteers will qualify if they meet the following criteria
- 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.
- 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.
- Obesity, defined as body mass index (BMI) greater than or equal to 30 kg/m2 and weight under 450 lbs, in order for subjects to be able to undergo DXA scanning.
- 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).
- 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.
- 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).
Who cannot join
- Volunteers will be excluded (and referred to non-experimental treatment programs as needed) for the following reasons:
- 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 (e.g. -PT/PTT values that are prolonged greater than or equal to 3 seconds from the upper limit of the normal or thrombocytopenia < 70,000) or pulmonary disorders; or porphyria;
- Current users of tobacco products;
- Subjects following a diet with specific food requirements such as vegetarian, vegan, or kosher;
- Women who are pregnant or who are currently nursing an infant or have irregular menses;
- 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;
Show all 13Show fewer
- Recent (3 months) use of anorexiant medications;
- Subjects using medications known to affect glucose and fatty acid metabolism and/or absorption;
- Subjects on anticoagulatns, or those who cannot safely stop NSAIDs or antiplataelet agents for 10 days (a week prior to and three days after their biopsy)
- Subjects with weight change of more than 3% of body weight in the past two months;
- Subjects currently using a weight loss diet;
- Subjects with untreated hypertension: a consistently (2 weeks apart) elevated systolic blood pressure of greater than 160 mm Hg and/or a diastolic flood pressure greater than 95 mm Hg.
- Subjects with a history of keloid formation, since such individuals may have greater scarring after biopsies or intravenous catheter placement.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Fat Metabolism and Function Altering Polymorphisms in MC3R
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.
Read more
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.
Read the 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.
- Conditions
- Obesity, Healthy Volunteers
- Keywords
- Lipogenesis, Adult, Obesity, LIPOLYSIS, Melanocortin-3 Receptor
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Double-Variant MC3R | Volunteers with homozygous polymorphisms causing protein changes to T6K and V81I. | |
| Wild Type MC3R | Volunteers with no polymorphisms in MC3R gene. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Free fatty acid reflux rate measured on a high- fat diet during the hyperinsulinemic state
FFA flux by isotopic study
Measured: 3 hours
Secondary outcomes (1)
Free fatty acid flux rate in the post-absorptive state and estimates of whole body glucose disposal and endogenous glucose production assessed during postabsorptive and hyperinsulinemic states on both diets
FFA flux by isotopic study
Measured: 4 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2013 (estimated)
- Study start23 Sep 2013
- Primary completion13 Oct 2020
- Study completion28 Jun 2021
Why it stopped: Slow/Insufficient accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)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
- Prospective
- Enrolment
- 88 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
- NCT01851421
- Sponsor's protocol ID
- 130097
- Other IDs
- 13-CH-0097
- Status last verified
- Jun 2021
- First submitted
- 9 May 2013
- Last updated
- 30 Jun 2021
- Results posted
- No
Publications
Feng N, Young SF, Aguilera G, Puricelli E, Adler-Wailes DC, Sebring NG, Yanovski JA. Co-occurrence of two partially inactivating polymorphisms of MC3R is associated with pediatric-onset obesity. Diabetes. 2005 Sep;54(9):2663-7. doi: 10.2337/diabetes.54.9.2663.
PubMed 16123355Lee B, Koo J, Yun Jun J, Gavrilova O, Lee Y, Seo AY, Taylor-Douglas DC, Adler-Wailes DC, Chen F, Gardner R, Koutzoumis D, Sherafat Kazemzadeh R, Roberson RB, Yanovski JA. A mouse model for a partially inactive obesity-associated human MC3R variant. Nat Commun. 2016 Jan 28;7:10522. doi: 10.1038/ncomms10522.
PubMed 26818770Demidowich AP, Parikh VJ, Dedhia N, Branham RE, Madi SA, Marwitz SE, Roberson RB, Uhlman AJ, Levi NJ, Mi SJ, Jun JY, Broadney MM, Brady SM, Yanovski JA. Associations of the melanocortin 3 receptor C17A + G241A haplotype with body composition and inflammation in African-American adults. Ann Hum Genet. 2019 Sep;83(5):355-360. doi: 10.1111/ahg.12315. Epub 2019 Apr 2.
PubMed 30937899
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fat Metabolism and Function Altering Polymorphisms in MC3R
- ClinicalTrials.gov ID
- NCT01851421
- Acronym / sponsor ID
- 130097
- Conditions
- Obesity, Healthy Volunteers
- Keywords
- Lipogenesis, Adult, Obesity, LIPOLYSIS, Melanocortin-3 Receptor
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Slow/Insufficient accrual
- Enrolment
- 88 participants (actual)
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- 23 Sep 2013 (actual)
- Primary completion
- 13 Oct 2020 (actual)
- Study completion
- 28 Jun 2021 (actual)
- First posted
- 10 May 2013 (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:
- 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.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Double-Variant MC3R | – | –Volunteers with homozygous polymorphisms causing protein changes to T6K and V81I. |
| Wild Type MC3R | – | –Volunteers with no polymorphisms in MC3R gene. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Comunity sample
Key inclusion criteria (7 listed)
- Volunteers will qualify if they meet the following criteria
- 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.
- 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.
- Obesity, defined as body mass index (BMI) greater than or equal to 30 kg/m2 and weight under 450 lbs, in order for subjects to be able to undergo DXA scanning.
- 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).
Key exclusion criteria (13 listed)
- Volunteers will be excluded (and referred to non-experimental treatment programs as needed) for the following reasons:
- 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 (e.g. -PT/PTT values that are prolonged greater than or equal to 3 seconds from the upper limit of the normal or thrombocytopenia < 70,000) or pulmonary disorders; or porphyria;
- Current users of tobacco products;
- Subjects following a diet with specific food requirements such as vegetarian, vegan, or kosher;
- Women who are pregnant or who are currently nursing an infant or have irregular menses;
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
Free fatty acid reflux rate measured on a high- fat diet during the hyperinsulinemic state
Time frame: 3 hours
FFA flux by isotopic study
1 secondary outcome
Free fatty acid flux rate in the post-absorptive state and estimates of whole body glucose disposal and endogenous glucose production assessed during postabsorptive and hyperinsulinemic states on both diets
Time frame: 4 days
Results and safety
The study was stopped early (reason given: Slow/Insufficient accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2021.
- Background: PubMed 16123355Feng N, Young SF, Aguilera G, Puricelli E, Adler-Wailes DC, Sebring NG, Yanovski JA. Co-occurrence of two partially inactivating polymorphisms of MC3R is associated with pediatric-onset obesity. Diabetes. 2005 Sep;54(9):2663-7. doi: 10.2337/diabetes.54.9.2663.
- Background: PubMed 26818770Lee B, Koo J, Yun Jun J, Gavrilova O, Lee Y, Seo AY, Taylor-Douglas DC, Adler-Wailes DC, Chen F, Gardner R, Koutzoumis D, Sherafat Kazemzadeh R, Roberson RB, Yanovski JA. A mouse model for a partially inactive obesity-associated human MC3R variant. Nat Commun. 2016 Jan 28;7:10522. doi: 10.1038/ncomms10522.
- Background: PubMed 30937899Demidowich AP, Parikh VJ, Dedhia N, Branham RE, Madi SA, Marwitz SE, Roberson RB, Uhlman AJ, Levi NJ, Mi SJ, Jun JY, Broadney MM, Brady SM, Yanovski JA. Associations of the melanocortin 3 receptor C17A + G241A haplotype with body composition and inflammation in African-American adults. Ann Hum Genet. 2019 Sep;83(5):355-360. doi: 10.1111/ahg.12315. Epub 2019 Apr 2.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Obesity and Healthy Volunteers, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
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 7 inclusion and 13 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: stopped early, as of the sponsor's last update on 30 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 was stopped early (reason given: Slow/Insufficient accrual). Results are not available in the source record.
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?
Free fatty acid reflux rate measured on a high- fat diet during the hyperinsulinemic state (time frame: 3 hours). 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 NCT01851421, which also lists 3 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 30 Jun 2021.