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Cold Induced Changes in White Adipose

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ClinicalTrials.gov Identifier: NCT02596776
Recruitment Status : Recruiting
First Posted : November 4, 2015
Last Update Posted : May 8, 2018
Sponsor:
Collaborator:
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Philip Kern, University of Kentucky

Brief Summary:

An adaptation to a cold environment is a tendency to generate heat within our body. Some of this heat comes from our fat tissue. Although most fat tissue is "white fat", there are pockets deep within the body that are called "brown fat", which are specially adapted to burning fat and making heat. The investigator believes that our white fat, just underneath the surface of our skin, also has this property to burn fat and make heat, although not at the high level of brown fat. This study is to examine this fat-burning property of the white fat under the skin in response to seasons and to cold. Many such studies have been done in mice, but little has been done in humans.

There are a number of factors, including age, weight, and medical history, that may make a person eligible or ineligible to participate in this study. Certain medications could make a person ineligible, but if these medications can be safely altered, the individual may become eligible.


Condition or disease Intervention/treatment Phase
Obese Normal Body Weight Prediabetes Metabolic Syndrome Procedure: Fat biopsy Drug: Propranolol and fat biopsy Other: heavy water and fat biopsy Early Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Cold Induced Changes in Human Subcutaneous White Adipose
Study Start Date : March 2016
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Biopsy
Drug Information available for: Propranolol

Arm Intervention/treatment
Active Comparator: Fat biopsy
From each abdominal and thigh biopsy, between 0.5 - 3 g of tissue is obtained (often less from the thigh), which is used for immunohistochemistry and frozen for subsequent RNA or protein isolation.
Procedure: Fat biopsy
up to 16 biopsy samples will be taken from each subject

Experimental: Propranolol and Fat Biopsy
From each abdominal and thigh biopsy, tissue will be examined for gene expression, with a focus on genes believed to be involved in adipose beiging (PGC1α, UCP1, TMEM26, IL4, Metrnl, CPA3, Siglec 8, tyrosine hydroxylase, others), and with immunohistochemistry, with a focus on beige adipocytes, macrophages, eosinophils and mast cells.
Procedure: Fat biopsy
up to 16 biopsy samples will be taken from each subject

Drug: Propranolol and fat biopsy
subset of subjects will receive propranolol and have fat biopsy performed

Active Comparator: Heavy Water and Fat Biopsy
The investigator will measure in vivo adipose lipolysis and triglyceride (TG) turnover in response to cold to physiologically demonstrate the impact of cold exposure on tissue function. The subjects will then be given 50 mL sterile containers of 70% 2H2O and consume two 50 mL vials per day during the remainder of the 5-week labeling period. Plasma and urine will be collected weekly so that body 2H2O can be measured.
Procedure: Fat biopsy
up to 16 biopsy samples will be taken from each subject

Other: heavy water and fat biopsy
subset of subjects will be given heavy water and have fat biopsy performed




Primary Outcome Measures :
  1. WAT changes during repeated exposure to cold temperatures [ Time Frame: 28 Weeks (Summer and Winter Seasons) ]
    Adipose biopsies will be performed

  2. WAT changes following Propranolol dosing [ Time Frame: 17 days in the summer season ]
    Subjects will be prescribed propranolol and adipose biopsies will be obtained.

  3. In vivo measurement of adipose lipolysis and triglyceride (TG) turnover [ Time Frame: 5 weeks per season (summer and winter) ]
    The heavy water will be given to and adipose biopsies will be obtained.



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Ages Eligible for Study:   35 Years to 60 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • the lean subjects body mass index (BMI) < 27
  • subjects with obesity/MetS (BMI 27-45 with IGT, IFG, or 3 features of MetS)
  • Insulin resistance Fasting blood sugar >126, or 2 hr glu >200, but with A1C<7.5 (i.e. we will include subjects with T2DM on no meds and with good glycemic control)
  • adequate platelet count (>100,000)
  • hematocrit of >32
  • stable weight

Exclusion Criteria:

  • obese subjects (BMI > 45)
  • anti-inflammatory drugs, β-blockers, any diabetes drugs or drugs known to affect adipose tissue
  • an unstable medical condition
  • coronary artery disease
  • congestive heart failure
  • heart block or a history of or any contraindication to a β-blocker.
  • asthma
  • previous stroke
  • use of anticoagulants or aspirin
  • pregnant or breastfeeding
  • lifestyles involving absent or extreme temperature exposure (eg. homebound or institutionalized subjects, outdoor workers).

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): NCT02596776


Contacts
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Contact: Philip Kern, MD (859) 323-4933 ext 81394 pake222@uky.edu

Locations
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United States, Kentucky
University of Kentucky Medical Center Center for Clinical and Translational Science Recruiting
Lexington, Kentucky, United States, 40536
Contact: Brianna Harfmann, PhD    859-218-1362    harfmanndb@uky.edu   
Sponsors and Collaborators
Philip Kern
National Institutes of Health (NIH)
Investigators
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Principal Investigator: Philip Kern, MD University of Kentucky

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Philip Kern, Principal Investigator, University of Kentucky
ClinicalTrials.gov Identifier: NCT02596776     History of Changes
Other Study ID Numbers: 15-0663
First Posted: November 4, 2015    Key Record Dates
Last Update Posted: May 8, 2018
Last Verified: May 2018

Additional relevant MeSH terms:
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Metabolic Syndrome
Body Weight
Prediabetic State
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Signs and Symptoms
Diabetes Mellitus
Endocrine System Diseases
Propranolol
Deuterium Oxide
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Antihypertensive Agents
Vasodilator Agents
Antineoplastic Agents
Radiation-Protective Agents
Protective Agents