Clinical trial NCT02927392: Brown Adipose Tissue Activity in Pre- and Postmenopausal Women
Official title: The Impact of Estrogen Status on the Biological Function of Brown Adipose Tissue in Women Measured Using Quantitative PET/CT
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Menopause
Obesity
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: University of Ottawa
name: Université de Sherbrooke
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2016-10-07
Enrollment: 69
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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.

Eligibility 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.

Primary outcomes:
measure: Brown Adipose Tissue Volume
timeFrame: 5-6 hrs
measure: Brown Adipose Tissue Activity -Warm Exposure
timeFrame: 5-6 hrs
measure: Brown Adipose Tissue Activity - ColdExposure
timeFrame: 5-6 hrs
Secondary outcomes:
measure: Resting Energy Expenditure - Before Cold Exposure
timeFrame: 5-6 hrs.
measure: Resting Energy Expenditure - After Cold Exposure
timeFrame: 5-6 hrs
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Edward Melanson, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: