Understanding the Roles of Hormones in Adipocyte Remodeling Following Menopause (RESUME-2)
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|ClinicalTrials.gov Identifier: NCT03856268|
Recruitment Status : Suspended (Temporarily paused due to COVID-19 and expected to resume.)
First Posted : February 27, 2019
Last Update Posted : May 20, 2020
The overarching aims of this study are to:
- 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).
- 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).
|Condition or disease||Intervention/treatment|
|Menopause Surgical Estrogen Deficiency Adiposity Follicle-Stimulating Hormone Deficiency Hormone Deficiency||Procedure: 'Surgical Menopause' Group Drug: 'Drug-Induced Menopause' Group|
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.
|Study Type :||Observational|
|Estimated Enrollment :||12 participants|
|Official Title:||Understanding the Roles of Estradiol and Follicle-stimulating Hormone in Adipocyte Remodeling Following Surgical and Pharmacology-induced Menopause (RESUME-2 Study)|
|Actual Study Start Date :||April 1, 2019|
|Estimated Primary Completion Date :||December 31, 2020|
|Estimated Study Completion Date :||March 31, 2021|
ARM 1: 'Surgical Menopause' Group
Premenopausal women having an oophorectomy.
Procedure: 'Surgical Menopause' Group
Women undergoing laparoscopic oophorectomy surgery ('surgical menopause') will be enrolled at Pennington Biomedical.
Other Name: 'Bilateral Oophorectomy Surgery' Group
ARM 2: "Drug-Induced Menopause'
Premenopausal women with gonadal suppression
Drug: 'Drug-Induced Menopause' Group
Women undergoing gonadal suppression via leuprolide acetate (Lupron [AbbVie Inc.]) will be enrolled at the University of Colorado-Denver.
Other Name: 'Pharmacology-Induced Menopause' Group
'Comparative (Control)' Group
Premenopausal women with regular cycles.
- Rate of in vivo adipogenesis (via deuterium-enrichment of adipose tissue DNA) [ Time Frame: Change from baseline in enrichment of DNA of adipose cells with deuterium at 8 weeks ]Deuterium from the deuterium-labeled water is incorporated into the newly-synthesized DNA of newly-formed fat cell precursor cells through cell replication. The latter carry over the label when they become fat cells through differentiation. Enzymatic digestion of the fat tissue isolates the individual cells constituting the fat tissue. Centrifugation of the cell suspension allows the separation of fat cells into a floating layer and a pellet comprised of stromal-vascular cells including the fat cell precursor cells and small fat cells. As the fat cell precursor cells and small adipocytes have the property to attach quickly to plastic surfaces of culture dishes, a brief culturing of the stromal-vascular cells sorts these cells from the remaining cells. Thus, measuring the deuterium-enrichment of DNA from plastic-adherent stromal-vascular cells indicates the rate of in vivo formation of new mature fat cells and pre-adipocytes, a process collectively termed adipogenesis.
- Size of adipocytes [ Time Frame: Change from baseline in size of adipocytes at 8 weeks post-surgery ]Fat cell size will be determined using osmium fixation of the lipids and measurement of their diameter with Coulter Counter followed by calculation of fat cell volume. The mean lipid content of fat cells will be calculated by multiplying the fat cell volume by the density of triolein (0.915).
- Number of adipocytes [ Time Frame: Change from baseline in number of adipocytes at 8 weeks post-surgery ]Fat cell number will be estimated by dividing the volume of adipose tissue depot of interest to the mean fat cell volume or the fat mass of the depot to the mean lipid content in fat cell.
- Body composition (by Dual-energy X-ray Absorptiometry (DXA)) [ Time Frame: Change from baseline in body composition at 8 weeks post-surgery ]Fat mass, fat-free mass, and percent body fat will be assessed using a whole-body scanner GE iDXA.
- Adipose tissue gene and protein expression [ Time Frame: Changes from baseline in gene and protein expression at 8 weeks post-surgery ]Expression levels of genes and proteins involved in adipocyte expansion and function (ERα, PPARγ2, C/EBPα, aromatase, adiponectin, and LPL), extracellular matrix remodeling and fibrosis (COL6(a1, a2, a3), COL4a1, and TGFβ), and inflammation (IL-6 and TNFα) will be assessed.
Biospecimen Retention: Samples With DNA
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): NCT03856268
|United States, Louisiana|
|Pennington Biomedical Research Center|
|Baton Rouge, Louisiana, United States, 70808|
|Principal Investigator:||Kara L Marlatt, PhD, MPH||Pennington Biomedical Research Center|