NCT02596776

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
26

participants targeted

Target at P25-P50 for early_phase_1

Timeline
Completed

Started Mar 2016

Typical duration for early_phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 2, 2015

Completed
2 days until next milestone

First Posted

Study publicly available on registry

November 4, 2015

Completed
4 months until next milestone

Study Start

First participant enrolled

March 1, 2016

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 20, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 20, 2018

Completed
Last Updated

February 7, 2020

Status Verified

February 1, 2020

Enrollment Period

2.5 years

First QC Date

November 2, 2015

Last Update Submit

February 5, 2020

Conditions

ObeseNormal Body WeightPrediabetesMetabolic Syndrome

Outcome Measures

Primary Outcomes (3)

  • WAT changes during repeated exposure to cold temperatures

    Adipose biopsies will be performed

    28 Weeks (Summer and Winter Seasons)

  • WAT changes following Propranolol dosing

    Subjects will be prescribed propranolol and adipose biopsies will be obtained.

    17 days in the summer season

  • In vivo measurement of adipose lipolysis and triglyceride (TG) turnover

    The heavy water will be given to and adipose biopsies will be obtained.

    5 weeks per season (summer and winter)

Study Arms (3)

Fat biopsy

ACTIVE COMPARATOR

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

Propranolol and Fat Biopsy

EXPERIMENTAL

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 biopsyDrug: Propranolol and fat biopsy

Heavy Water and Fat Biopsy

ACTIVE COMPARATOR

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 biopsyOther: heavy water and fat biopsy

Interventions

Fat biopsyPROCEDURE

up to 16 biopsy samples will be taken from each subject

Fat biopsyHeavy Water and Fat BiopsyPropranolol and Fat Biopsy
Propranolol and fat biopsyDRUG

subset of subjects will receive propranolol and have fat biopsy performed

Propranolol and Fat Biopsy
heavy water and fat biopsyOTHER

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

Heavy Water and Fat Biopsy

Eligibility Criteria

Age35 Years - 60 Years
Sexfemale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Kentucky Medical Center Center for Clinical and Translational Science

Lexington, Kentucky, 40536, United States

Location

Related Publications (2)

  • Finlin BS, Memetimin H, Confides AL, Kasza I, Zhu B, Vekaria HJ, Harfmann B, Jones KA, Johnson ZR, Westgate PM, Alexander CM, Sullivan PG, Dupont-Versteegden EE, Kern PA. Human adipose beiging in response to cold and mirabegron. JCI Insight. 2018 Aug 9;3(15):e121510. doi: 10.1172/jci.insight.121510. eCollection 2018 Aug 9.

    PMID: 30089732RESULT

  • Thiagarajan D, Quadri N, Jawahar S, Zirpoli H, Del Pozo CH, Lopez-Diez R, Hasan SN, Yepuri G, Gugger PF, Finlin BS, Kern PA, Gabbay K, Schmidt AM, Ramasamy R. Aldose reductase promotes diet-induced obesity via induction of senescence in subcutaneous adipose tissue. Obesity (Silver Spring). 2022 Aug;30(8):1647-1658. doi: 10.1002/oby.23496.

    PMID: 35894077DERIVED

MeSH Terms

Conditions

ObesityPrediabetic StateMetabolic Syndrome

Interventions

PropranololDeuterium Oxide

Condition Hierarchy (Ancestors)

OverweightOvernutritionNutrition DisordersNutritional and Metabolic DiseasesBody WeightSigns and SymptomsPathological Conditions, Signs and SymptomsDiabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesEndocrine System DiseasesInsulin ResistanceHyperinsulinism

Intervention Hierarchy (Ancestors)

PhenoxypropanolaminesPropanolaminesAmino AlcoholsAlcoholsOrganic ChemicalsPropanolsAminesNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsPolycyclic CompoundsWaterHydroxidesAlkaliesInorganic ChemicalsAnionsIonsElectrolytesDeuteriumHydrogenElementsGases

Study Officials

  • Philip Kern, MD

    University of Kentucky

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
early phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

November 2, 2015

First Posted

November 4, 2015

Study Start

March 1, 2016

Primary Completion

August 20, 2018

Study Completion

August 20, 2018

Last Updated

February 7, 2020

Record last verified: 2020-02

Data Sharing

IPD Sharing
Will not share

Locations

US(1)