Clinical trial NCT03856268: Understanding the Roles of Hormones in Adipocyte Remodeling Following Menopause
Official title: Understanding the Roles of Estradiol and Follicle-stimulating Hormone in Adipocyte Remodeling Following Surgical and Pharmacology-induced Menopause (RESUME-2 Study)
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Menopause Surgical
Estrogen Deficiency
Adiposity
Follicle-Stimulating Hormone Deficiency
Hormone Deficiency
Lead sponsor: Pennington Biomedical Research Center
Sponsor class: OTHER
Collaborators: name: University of Colorado, Denver
name: University of Alabama at Birmingham
First posted: 2019-02-27
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Women (aged 18-50 y) will be enrolled. Women will be pre-menopausal, not pregnant, and not using hormone therapy or have medical indication for increased cancer risk.

Brief summary: The overarching aims of this study are to:

1. Characterize the rate of in vivo adipogenesis, and changes in adipose tissue gene and protein expression, in the scABD and scFEM depots of women undergoing surgical menopause (↓E2, ↑FSH).
2. Characterize the rate of in vivo adipogenesis, and changes in adipose tissue gene and protein expression, in the scABD and scFEM depots of women undergoing gonadal suppression (↓E2, ↓FSH).

Detailed description: This is a cross-sectional study where two groups of premenopausal women (ages 18-50 y) will be enrolled in a parallel arm study:

* Arm 1 (Surgical Menopause): up to 6 women undergoing laparoscopic, elective bilateral oophorectomy \[Site: Pennington Biomedical Research Center\].
* Arm 2 (Pharmacology-Induced Menopause): up to 6 women undergoing gonadal suppression via leuprolide acetate (Lupron \[AbbVie Inc.\]) \[Site: UC-Denver\].

We will compare each arm of women to non-oophorectomized, premenopausal women (controls) with normal menstrual cycles (Apple\&Pear study; NCT01748994; PI: Ravussin) selectively matched (1:2) for age and BMI. The Apple\&Pear study uses the same in vivo adipogenesis labeling protocol, with similar age and BMI criteria, as the proposed study.

Eligibility criteria: INCLUSION CRITERIA:

* Healthy female
* Ages 18-50 y
* Planning to have either a laparoscopic bilateral oophorectomy or a laparoscopic unilateral oophorectomy (which would result in no remaining ovaries)
* Are willing to drink heavy water (2H2O) over an 8-week period
* Medically cleared for participation in the study by OB/GYN and Medical Investigator
* Are willing to have blood and fat tissue stored for future use

EXCLUSION CRITERIA:

* Meet either of the following criteria:
* Have all 3 of the major menopause-related symptoms \[hot flashes, mood swings, insomnia (trouble sleeping)\]
* Have 2 of the major menopause-related symptom combinations \[hot flashes and mood swings, or hot flashes and insomnia (trouble sleeping)\]
* Unstable weight in the last 3 months \[gain or loss \>7 lb (or 3.2 kg)\]
* History of clinically diagnosed diabetes or a fasting blood glucose \>126 mg/dL
* Chronic use of systemic glucocorticoids, antipsychotic/antidepressant medications, thiazolidinediones and other medications that cause clinically significant weight gain, weight loss or are known to make changes in fat cell number/size \*
* Previous bariatric surgery (or other surgeries) for obesity or weight loss (\< 3 years ago)
* Use of over the counter or prescription weight loss products
* History of metabolic diseases (other than diabetes)
* History of neurological disease
* History of cardiovascular disease (or other chronic diseases)
* Pregnant, planning to become pregnant, or breastfeeding
* Use of hormone replacement therapy
* Unwilling to discontinue any form or hormonal therapy (e.g., contraceptives including birth control pills, vaginal ring, injections, implant, or skin patch; hormonal supplements, etc.) upon enrollment (after the Screening Visit).

  * Inconsistent use of medications listed above will be evaluated and left up to the discretion of the Medical Investigator to evaluate safety.

Primary outcomes:
measure: Rate of in vivo adipogenesis (via deuterium-enrichment of adipose tissue DNA)
timeFrame: Change from baseline in enrichment of DNA of adipose cells with deuterium at 8 weeks
Secondary outcomes:
measure: Size of adipocytes
timeFrame: Change from baseline in size of adipocytes at 8 weeks post-surgery
measure: Number of adipocytes
timeFrame: Change from baseline in number of adipocytes at 8 weeks post-surgery
measure: Body composition (by Dual-energy X-ray Absorptiometry (DXA))
timeFrame: Change from baseline in body composition at 8 weeks post-surgery
measure: Adipose tissue gene and protein expression
timeFrame: Changes from baseline in gene and protein expression at 8 weeks post-surgery
Other outcomes:
Locations:
city: Baton Rouge
country: United States
facility: Pennington Biomedical Research Center
state: Louisiana
Study officials:
affiliation: Pennington Biomedical Research Center
name: Kara L Marlatt, PhD, MPH
role: PRINCIPAL_INVESTIGATOR
References: