Circadian Brown Adipose Tissue Metabolism

October 25, 2016 updated by: Daniel Pryma, University of Pennsylvania

A Pilot Study to Investigate Circadian Variations in Brown Adipose Tissue Metabolism in Healthy Volunteers.

Brown adipose tissue is poorly understood fat that can metabolize glucose in order to generate heat. Since activated brown fat has a high metabolic rate, it is of great interest as a potential target to combat obesity. However, the signaling and control of brown fat metabolism is poorly understood. Because brown fat uses glucose as its energy source, brown fat metabolism can be imaged with PET/CT using the positron emitting glucose analog F-18 FDG. We have recently shown in mice a striking circadian variation in brown fat metabolism as evidenced by changes in FDG uptake. In this study we endeavor to generate pilot data on a potential circadian variation in brown fat activation in healthy humans.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Brown adipose tissue is a form of fat that is able to metabolize glucose in order to generate heat. When active, it can convert a great deal of glucose into thermal energy. Activation of brown fat could potentially help to combat obesity by increasing the basal metabolic rate. However, activation and signaling of brown fat is poorly understood. In a mouse model, we have recently shown that there is significant circadian variation in brown fat activation and have also discovered the gene that is responsible for the circadian changes (Gerhart-Hines et al, Nature 2013). Specifically, we have shown that in wild type mice, brown fat activation is high at night and low during the day. Whether human brown fat activation has a circadian component is currently unknown. Showing that brown fat activation in humans is subject to similar circadian rhythms as in mice would be an important step in understanding the signaling of activation and may help to elucidate potential strategies to control activation. Positron emission tomography/computed tomography (PET/CT) is a hybrid imaging modality that allows imaging positron emitting isotopes such as fluorine-18 (F-18) along with anatomic imaging using x-rays. The physiologic information from the PET component is co-registered with the anatomic information from the CT component, permitting accurate localization and quantification of physiologic processes. The most common clinically used positron emitting radiopharmaceutical is F-18 fluorodeoxyglucose (FDG). It is a glucose analog which is taken up by glucose transporters and phosphorylated to FDG-6P by hexokinase. However, isomerase, the next enzyme in the glycolytic pathway, is inactive on FDG-6P and so it is largely trapped in the cell. Therefore, FDG PET/CT gives a map of relative amount of glucose uptake and phosphorylation over the interval from injection to scan. Activated brown fat has robust FDG uptake with very intense signal seen. Therefore, FDG PET/CT can be used both to determine whether a person has activated brown fat at the time of the scan as well as to quantify the overall level of metabolism in the fat. Our primary objective is to gather pilot data on the potential presence of circadian variations in brown fat uptake in young, healthy, lean male volunteers. We plan to do this by performing two FDG PET/CT scans 12 hours apart while the patient remains in a temperature and diet controlled environment leading up to both scans. Our primary hypothesis is that brown fat activity will be higher during the day than at night (as human and mouse circadian rhythms are reversed). We will also pair measurement of cortisol with the FDG injections as cortisol levels provide valuable independent information on the circadian rhythm.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
10

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • At least 18 years of age and less than 45 years of age
  • Able and willing to provide informed consent
  • Male gender
  • Capable of complying with study procedures and able to lie still in the PET/CT scanner for up to 40 minutes continuously
  • Normal fasting glucose (less than 100 mg/dl)
  • No evidence of significant concurrent illness
  • Follow typical sleep/wake cycle of generally asleep at night and awake during the day

Exclusion Criteria:

  • Prior surgery or radiation to the head, neck, or upper chest (except surgeries such as tonsillectomy/adenoidectomy/tympanostomy that would not be expected, in the judgement of the investigator, to have disrupted the adipose tissue in the neck or the upper chest)
  • Active addiction or illicit drug abuse
  • BMI greater than 25
  • Employment in the night shift/3rd shift
  • Unable to remain in the Clinical and Translational Research Center (CTRC) for entire 24 hour period.
  • Unable or unwilling to maintain peripheral intravenous access for up to 24 hours
  • Abnormal liver or kidney function (serum creatinine or transaminase levels greater than 1.5 ULN)
  • Subject has any other condition or personal circumstance that, in the judgement of the investigator, might interfere with the collection of complete, high quality data

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: Single group assignment
Diagnostic test/procedure - FDG PET/CT
Device: FDG PET/CT
PET/CT is a hybrid imaging modality that allows imaging positron emitting isotopes such as F-18 along with anatomic imaging using x-rays. The physiologic information from the PET component is co-registered with the anatomic information from the CT component, permitting accurate localization and quantification of physiologic processes. The most common clinically used positron emitting radiopharmaceutical is F-18 fluorodeoxyglucose (FDG). It is a glucose analog which is taken up by glucose transporters and phosphorylated to FDG-6P by hexokinase. FDG PET/CT gives a map of relative amount of glucose uptake and phosphorylation over the interval from injection to scan.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Change in Maximum Standardized Update Value (SUVmax) in Brown Adipose Tissue FDG Uptake in the Neck or Upper Chest on Evening and Imaging Compared to Morning Imaging
Time Frame: ~12-hours
~12-hours

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Correlation Between Cortisol Level and Brown Adipose Tissue FDG Uptake
Time Frame: ~12-hours
~12-hours
Change in Total Brown Adipose Tissue FDG Uptake as Measured by Total Volume of Segmented Fat Times the Mean Standardized Uptake Value (SUVmean)
Time Frame: ~12-hours
~12-hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Pennsylvania

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 4, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 5, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 6, 2014

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 7, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 25, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2016

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 819607

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