The Physiology of Human Brown Adipose Tissue

Obesity Clinical Trial

Official title:

The Physiology of Human Brown Adipose Tissue

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04352244
• Other study ID #: 2009P-000101
• Status: Recruiting
• Start date: March 5, 2020
• Est. completion date: March 2024

Study information

• Verified date: July 2023
• Source: Beth Israel Deaconess Medical Center
• Contact: Mary Elizabeth Patti, MD
• Phone: 6173092635
• Email: MaryElizabeth.Patti[@]joslin.harvard.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Brown fat is a type of fat, found in both children and adults, which can produce heat and regulate the body's metabolism and energy use. White fat is the more common type of fat which is used to store extra calories. Understanding more about differences between brown and white fat may allow us to develop new approaches to improve the body's metabolism.

Description:

The overarching goal of this study, is to map fat (adipose) tissue differences in humans. The investigators will probe multiple aspects of fat cell (adipocyte) identity by integrating quantitative chemical imaging, single-cell and single-nucleus RNA sequencing (sc and snRNAseq), and site-specific collection of adipocytes and adipocyte precursors. Deidentified data from these studies will be submitted to the Human Cell Atlas. The investigators anticipate that these studies will ultimately increase understanding of mechanisms by which fat (adipose) tissue regulates systemic metabolism (energy transformation in the body), and promotes risk for metabolic disease. Knowledge gained from this research may be used to set the stage for disease-specific analyses, and aid in the development of personalized medicine for metabolic diseases such as type 2 diabetes.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: March 2024
• Est. primary completion date: March 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion criteria:

1. Healthy participants between age 18 and 75 years undergoing planned clinically indicated procedure at BIDMC.

Exclusion Criteria:

1. Body mass index (BMI) greater than or equal to 40 kg/m2

2. History of any local or systemic infectious disease with fever or requiring antibiotic within four weeks of drug administration;

3. Diabetes, either previously diagnosed or hemoglobin A1c greater than or equal to 6.5%

4. Use of oral or parenteral corticosteroids (epidural permitted) or other medication known to cause insulin resistance in the previous 6 weeks.

5. Willingness to provide informed consent and follow study procedures, including attending scheduled visits.

6. Chronic kidney disease stage 4 or 5 (including end-stage renal disease);

7. Hepatic disease, including serum alanine aminotransferase (ALT) or aspartate transaminase (AST) greater than or equal to 3 times the upper limit of normal; hepatic synthetic insufficiency as defined as serum albumin < 3.0 g/dL; or serum bilirubin > 2.0;

8. Active malignancy (except squamous or basal cell carcinoma of skin)

9. Bleeding disorder, treatment with anticoagulants (if not discontinued prior to surgery), or platelet count <50,000;

10. Current addiction to alcohol or substances of abuse;

11. Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation;

12. Use of an investigational drug within 30 days prior to screening.

13. There will be no involvement of special vulnerable populations such as fetuses, neonates, pregnant women, children, prisoners, institutionalized or incarcerated individuals, or others who may be considered vulnerable populations.

14. Because the goal is to study adult human brown adipose tissue, children are not eligible to participate.

Related Conditions & MeSH terms

• Adipose Tissue
• Adipose Tissue, Brown
• Obesity

Intervention

Procedure:
• Fat biopsy
The fat biopsy is performed during a scheduled procedure at the Beth Israel Deaconess Medical Center (BIDMC). Routine preoperative procedures will be followed, including local anesthesia (numbing a particular region of the body) or general anesthesia (being put to sleep). Adipose tissue will be sampled from different depots depending on the procedure. For example, the surgeon will collect adipose tissue from the neck and supraclavicular depots from cervical spine, thyroid, and parathyroid procedures; perinephric fat from adrenalectomies, omental fat from abdominal procedures, and paraspinal fat from lumbar spine procedures. Up to 5 pieces of fat tissue weighing about three to six grams will be removed. All other aspects of the surgical procedure will proceed as planned. Samples will be prepared for subsequent laboratory analysis.

Diagnostic Test:
• Blood sampling
A blood sample will be collected in the fasting state either during preoperative testing or in the preoperative area on the day of planned procedure for measurement of adipose functional markers (leptin, adiponectin) and insulin resistance (insulin, C-peptide), and measures of glycemia (glucose, hemoglobin A1c).

Genetic:
• Blood sample for DNA analysis
Targeted resequencing of DNA to identify variants associated with adipose phenotypes will be performed.

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Beth Israel Deaconess Medical Center	Chan Zuckerberg Initiative, Joslin Diabetes Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Collect human brown and white adipose tissue to prepare progenitor and differentiated cells for single nucleus RNA analysis.	Adipose tissue biopsy samples will be processed for single-nucleus RNA analysis of gene expression.	March 2022
Primary	Collect human brown and white adipose tissue to prepare progenitor and differentiated cells for Raman spectroscopy.	Adipose tissue biopsy samples will be processed for Raman spectroscopy analysis.	March 2022
Primary	Collect human brown and white adipose tissue to prepare cells for ex vivo differentiation	Adipose tissue biopsy samples will be processed for ex vivo differentiation.	March 2022
Primary	Insulin resistance	Insulin resistance of participants, assessed by homeostatic model of insulin resistance (HOMA-IR), will be analyzed and summarized.	March 2022
Primary	Hemoglobin A1c	Hemoglobin A1c levels for participants will be analyzed and summarized.	March 2022
Primary	Fasting glucose levels	Fasting glucose levels for participants will be analyzed and summarized.	March 2022
Primary	Body mass index (BMI)	Weight and height will be combined to report BMI in kg/m^2. BMI of participants will be analyzed and summarized.	March 2022
Primary	Demographic characteristics	Demographic characteristics of participants will be analyzed and summarized.	March 2022
Secondary	DNA analysis	DNA will be isolated and stored from blood samples. If specific genes are differentially regulated as a function of metabolic state or anatomical location of biopsy, locus-specific or genome-wide genotyping may be performed to assess potential regulatory single-nucleotide polymorphisms (SNP).	March 2022