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The Physiology of Human Brown Adipose Tissue

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04352244
Recruitment Status : Recruiting
First Posted : April 20, 2020
Last Update Posted : August 19, 2021
Sponsor:
Collaborators:
Joslin Diabetes Center
Chan Zuckerberg Initiative
Information provided by (Responsible Party):
Mary Elizabeth Patti, Beth Israel Deaconess Medical Center

Brief 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.

Condition or disease Intervention/treatment
Adipose Tissue, Brown Adipose Tissue Obesity Procedure: Fat biopsy Diagnostic Test: Blood sampling Genetic: Blood sample for DNA analysis

Detailed 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.

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Study Type : Observational
Estimated Enrollment : 40 participants
Observational Model: Other
Time Perspective: Cross-Sectional
Official Title: The Physiology of Human Brown Adipose Tissue
Actual Study Start Date : March 5, 2020
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : March 2022

Group/Cohort Intervention/treatment
Surgical Participants
Individuals undergoing abdominal surgery or radiologically-guided biopsies for clinical indications will be recruited prior to the planned procedures.
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.




Primary Outcome Measures :
  1. Collect human brown and white adipose tissue to prepare progenitor and differentiated cells for single nucleus RNA analysis. [ Time Frame: March 2022 ]
    Adipose tissue biopsy samples will be processed for single-nucleus RNA analysis of gene expression.

  2. Collect human brown and white adipose tissue to prepare progenitor and differentiated cells for Raman spectroscopy. [ Time Frame: March 2022 ]
    Adipose tissue biopsy samples will be processed for Raman spectroscopy analysis.

  3. Collect human brown and white adipose tissue to prepare cells for ex vivo differentiation [ Time Frame: March 2022 ]
    Adipose tissue biopsy samples will be processed for ex vivo differentiation.

  4. Insulin resistance [ Time Frame: March 2022 ]
    Insulin resistance of participants, assessed by homeostatic model of insulin resistance (HOMA-IR), will be analyzed and summarized.

  5. Hemoglobin A1c [ Time Frame: March 2022 ]
    Hemoglobin A1c levels for participants will be analyzed and summarized.

  6. Fasting glucose levels [ Time Frame: March 2022 ]
    Fasting glucose levels for participants will be analyzed and summarized.

  7. Body mass index (BMI) [ Time Frame: March 2022 ]
    Weight and height will be combined to report BMI in kg/m^2. BMI of participants will be analyzed and summarized.

  8. Demographic characteristics [ Time Frame: March 2022 ]
    Demographic characteristics of participants will be analyzed and summarized.


Secondary Outcome Measures :
  1. DNA analysis [ Time Frame: March 2022 ]
    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).


Biospecimen Retention:   Samples With DNA
Specimens to be retained: blood and adipose tissue samples.


Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Participants planning a procedure will be recruited from clinical practices of Dr. Andrew White, Dr. Peter Mowschenson, and Dr. Per-Olof Hasselgren at BIDMC.
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04352244


Contacts
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Contact: Mary Elizabeth Patti, MD 6173092635 MaryElizabeth.Patti@joslin.harvard.edu
Contact: Amanda L Sheehan, MSN 6173092695 amanda.sheehan@joslin.harvard.edu

Locations
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United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Andrew P White, MD    617-754-9000    apwhite@bidmc.harvard.edu   
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Joslin Diabetes Center
Chan Zuckerberg Initiative
Investigators
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Principal Investigator: Mary Elizabeth Patti, MD Joslin Diabetes Center
  Study Documents (Full-Text)

Documents provided by Mary Elizabeth Patti, Beth Israel Deaconess Medical Center:
Informed Consent Form  [PDF] December 9, 2019

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Responsible Party: Mary Elizabeth Patti, Associate Professor of Medicine, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT04352244    
Other Study ID Numbers: 2009P-000101
First Posted: April 20, 2020    Key Record Dates
Last Update Posted: August 19, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Deidentified participant data will be shared with other researchers with permission of local institutional review boards via the Human Cell Atlas database.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: 6 months after publication of study results
Access Criteria: Data will be shared with academic investigators with approval of local institutional review boards.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Mary Elizabeth Patti, Beth Israel Deaconess Medical Center:
Human Cell Atlas