Identification and Metabolic Characterization of a Cohort of Human Subjects With Mutations in PRDM-16

NCT02808715 | Completed

• 1 other identifier: 2014/337/C
• Study Type: observational
• Target: 247
• Locations: 0 countries
• Sites: N/A

Brief Summary

Chinese male subjects will be invited to participate in a research study of brown fat, a special tissue in the body that is designed to burn energy to make heat. The objective is to learn the importance of a gene called "PRDM-16" for the function of brown fat. Subjects were selected as a possible subject in this study because they fulfil the age and weight criteria. 500 subjects from the Singhealth Investigational Medicine Unit healthy volunteer database will be recruited over a period of 2 years. All of the subjects will have their PRDM-16 gene sequenced. The objective is to identify subjects with mutations, or changes, in their PRDM-16 gene. About 12 subjects with PRDM-16 mutations are expected to be identified. Samples of blood obtained during the course of this study will be stored and analysed only for the purposes of this study for a period not exceeding 2 years, and will be destroyed after completion of the study, unless subject is agreeable to donate the samples to the National Heart Centre Singapore for continuous storage for future studies that are approved by the institutional review board..

Conditions

Mutation; Obesity; Dyslipidemia; Diabetes

Outcome Measures

Primary Outcomes (1)

• Number of participants with deleterious mutations in the PRDM-16 locus, using standard genomic methods

  1 year

Interventions

Blood Sample Collection OTHER

Blood draw #1 Site of blood draw: IMU Volume of blood: 20mL Purpose of blood draw: Isolation of genomic DNA Site of storage: NHRIS biobank Coding: Specimens will be identified using a research ID that will be affixed to samples using bar-coding. After the blood is collected, stored the blood at 4 degree Celsius and contact the NHCS biobank coordinator to collect the blood samples. The blood samples must be collected within 1 hour of collection.

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

500 subjects will be recruited from the IMU healthy volunteer database. The investigators will enroll male Chinese volunteers. Women, children and the elderly are excluded from our initial study since prior research suggests that age and sex has an effect on brown fat function. In order to study the role of PRDM-16 in brown fat function the investigators wish to keep other contributing variables static in our study.

You may qualify if:

• Male
• Chinese
• Age \>= 21 and =\< 50
• BMI \>=18.5 and =\< 30
• Ability to provide written, informed consent.
• To control for this the investigators will include only adult Chinese men less than 50 years old.
• Since obesity also alters brown fat function the investigators will exclude those with BMI\>30.

You may not qualify if:

• Diagnosis of DM2
• Use of beta blockers, TZD (ie rosiglitazone/pioglitazone) or metformin Since the subjects will be recruited from the IMU healthy volunteer database there should be no prior history of DM2 or medication use. Nevertheless, diagnosis of DM2 and use of the drugs listed can alter brown fat activity and interfere with our analysis.
• Presence of pacemakers or foreign metallic objects in the eyes. Future planned experiments with the identified cohort include cardiac MRI. Subjects with pacemakers or foreign metallic objects in the eyes will be ineligible for this potential follow-up study.

Sponsors & Collaborators

• National Heart Centre Singapore: lead
• Duke-NUS Graduate Medical School: collaborator
• Singapore General Hospital: collaborator

Biospecimen

Retention: SAMPLES WITH DNA

A blood sample will be obtained and processed to isolate genomic DNA. A PCR-based strategy will be employed to sequence the entire PRDM-16 locus to identify variants. Variant alleles of PRDM-16 will be classified as having benign or deleterious mutations. Subjects who harbor deleterious mutations in both alleles of PRDM-16 will be identified for further study. For subjects who withdraw from the study, no further testing of the blood samples will occur. The blood will be stored at the NHRIS biobank. After the study is complete the samples will remain in storage at the NHRIS biobank.

MeSH Terms

Conditions

Obesity; Dyslipidemias; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Lipid Metabolism Disorders; Metabolic Diseases; Glucose Metabolism Disorders; Endocrine System Diseases

Study Officials

• Tan Ru San, MBBS

  National Heart Centre Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2016
• First Posted: June 22, 2016
• Study Start: May 1, 2014
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: June 22, 2016

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will not share