ClinicalTrials.gov
ClinicalTrials.gov Menu

Brown Adipose Tissue Activity in Pre- and Postmenopausal Women

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: NCT02927392
Recruitment Status : Recruiting
First Posted : October 7, 2016
Last Update Posted : July 14, 2017
Sponsor:
Collaborators:
University of Ottawa
Université de Sherbrooke
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
University of Colorado, Denver

Brief Summary:
The physiological relevance of brown adipose tissue (BAT) in humans is largely unknown. The investigators have shown that suppressing ovarian function in premenopausal women reduces resting energy expenditure (REE), and this is prevented by adding back estradiol (E2). The investigators preliminary data suggest that this may be due, in part, to reduced brown adipose tissue (BAT) activity. The overarching hypothesis is that BAT activity in humans is modulated by E2. To determine if natural declines in endogenous E2 contribute to changes in BAT activity, we will compare BAT activity in pre-and post-menopausal women. The investigators will also explore whether suppression of ovarian hormones in pre-menopausal women impairs BAT activity. BAT activity will be quantified using dynamic positron emission topography/computed tomography (PET/CT) imaging combined with 11C-acetate tracers. We will assess the thermogenic response of BAT by measuring cold-induced changes in REE, shivering, and skin and core temperature.

Condition or disease Intervention/treatment Phase
Menopause Obesity Drug: Leuprolide acetate Not Applicable

Detailed Description:

Participants will be asked to perform studies to measure resting metabolic rate and activity of brown adipose tissue or brown fat. Brown fat is different from regular "white fat" in that it produces heat and burns calories. The investigators will measure how active brown fat is at normal room temperature and after participants have been exposed to cold.

The study will last 5-6 hours. It will consist of measurements made in warm temperatures and then after a period of cold exposure. For the cold exposure part of the study, participants will be asked to wear a cooling suit for 3 hrs. Skin temperature is normally about 90º Fahrenheit. The cooling suit will adjust the water temperature until your skin temperature is about 82º Fahrenheit. The suit will cover the entire body except for the face, hands, and feet. Participants may feel cold while wearing the suit and you may shiver some, but based on past studies, any shivering should be minor.

Before and after the cooling suit is turned on, body scans will be performed using a procedure called positron emission tomography (PET). These scans do not use radiation. Before the PET scans, the investigators will infuse radioactive tracer into an arm. These tracers have a low dose of radiation and will show us where the brown fat is and how active it is. One PET scan will be performed at room temperature, and the second scan will be performed after the cooling suit has been worn for 3 hours. Two additional scans using computed tomography (CT) will be performed at end of the study. CT scans are like an x-ray, and use radiation. The radiation dose in the CT scan is much higher than the tracers. When the CT scans are combined with the PET scans, we can separate brown fat from white fat.

15 pre-menopausal women will be asked to volunteer for a follow up study. For 5 months, pre-menopausal women in this study will receive monthly injections that contain a study drug (leuprolide) that reduces estrogen to postmenopausal levels. This drug is approved by the FDA to reduce estrogen for the treatment of uterine fibroids and endometriosis, but is not approved for use in healthy women. In this study, the drug is being used to decrease hormones to determine if this reduces brown fat activity. 6 months after the first injection, these women will be asked to repeat the PET/CT studies.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: The Impact of Estrogen Status on the Biological Function of Brown Adipose Tissue in Women Measured Using Quantitative PET/CT
Study Start Date : January 2017
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : August 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Menopause

Arm Intervention/treatment
Experimental: Pre-menopausal women
To determine if natural declines in endogenous E2 contribute to changes in BAT activity, the investigators will compare BAT activity in pre-and post-menopausal women. We will also explore whether suppression of ovarian hormones in pre-menopausal women (using leuprolide acetate) impairs BAT activity.
Drug: Leuprolide acetate
A subset of premenopausal women will receive GnRHAG (leuprolide acetate) 3.75 mg/mo by intramuscular injection every 4 weeks for 24 weeks (6 doses).
Other Name: Lupron

No Intervention: Post-menopausal women
To determine if natural declines in endogenous E2 contribute to changes in BAT activity, the investigators will compare BAT activity in pre-and post-menopausal women.



Primary Outcome Measures :
  1. Brown Adipose Tissue Volume [ Time Frame: 5-6 hrs ]
    Brown adipose tissue volume will be measured using the radioactive tracer 18Fluro-deoxyglucose.

  2. Brown Adipose Tissue Activity -Warm Exposure [ Time Frame: 5-6 hrs ]
    Brown adipose tissue activity in warm temperatures will be measured using the radioactive tracer 11C-acetate

  3. Brown Adipose Tissue Activity - ColdExposure [ Time Frame: 5-6 hrs ]
    Brown adipose tissue activity after cold exposure will be measured using the radioactive tracer 11C-acetate


Secondary Outcome Measures :
  1. Resting energy expenditure - before cold exposure [ Time Frame: 5-6 hrs. ]
    Resting energy expenditure is the calories burned when a person is at rest.

  2. Resting energy expenditure - after cold exposure [ Time Frame: 5-6 hrs ]
    Resting energy expenditure is the calories burned when a person is at rest.



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.


Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Premenopausal volunteers will be healthy, eumenorrheic women, aged 18-45 yrs. Eumenorrheic status will be verified by regular menses (no missed cycles in previous year; cycle length 25-35 d).
  • Postmenopausal volunteers will be healthy women who have no menses for at least 12 months

Exclusion Criteria:

- Body mass index (BMI) > 35 kg/m2

Additional exclusion criteria for premenopausal women

  • Hormonal contraceptive use (past 6 mo.)
  • Pregnant, lactating or intention to become pregnant during the period of study

Additional exclusion criteria for postmenopausal women

  • History or current use of hormonal replacement therapy (HRT)
  • Women who have undergone surgical menopause.

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): NCT02927392


Contacts
Contact: Tracy Swibas, M.S. (303) 724-6418 tracy.swibas@ucdenver.edu
Contact: Edward Melanson, Ph.D. (303) 724-0935 ed.melanson@ucdenver.edu

Locations
United States, Colorado
University of Colorado Anschutz Medical Campus Recruiting
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
University of Ottawa
Université de Sherbrooke
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Principal Investigator: Edward Melanson, Ph.D. University of Colorado, Denver

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT02927392     History of Changes
Other Study ID Numbers: 16-1479
1R01DK112260-01 ( U.S. NIH Grant/Contract )
First Posted: October 7, 2016    Key Record Dates
Last Update Posted: July 14, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Additional relevant MeSH terms:
Leuprolide
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents