The Role of Estrogen in Adipocyte Remodeling Following Surgical Menopause (RESUME)
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|ClinicalTrials.gov Identifier: NCT03631680|
Recruitment Status : Suspended (Temporarily paused due to COVID-19 and expected to resume.)
First Posted : August 15, 2018
Last Update Posted : May 20, 2020
The overarching aim of this study is to assess the downstream effects of abrupt estrogen deficiency in women undergoing elective bilateral oophorectomy by studying:
- the rate of in vivo adipogenesis in the subcutaneous abdominal (scABD) and subcutaneous femoral (scFEM) adipose tissue depots following bilateral oophorectomy surgery using an innovative (and tested) 8-week incorporation of stable isotope (deuterium; 2H) administered in the form of heavy water (2H2O) to endogenously label adipose tissue DNA;
- the changes in expression of subcutaneous adipose tissue genes and proteins specific to adipocyte expansion and function; extracellular matrix remodeling and fibrosis; and inflammation in the scABD and scFEM depots before and after elective bilateral oophorectomy.
|Condition or disease||Intervention/treatment|
|Menopause Surgical Estrogen Deficiency Adiposity||Procedure: Bilateral Oophorectomy Surgery|
|Study Type :||Observational|
|Estimated Enrollment :||10 participants|
|Official Title:||The Role of Estrogen in Adipocyte Remodeling Following Surgical Menopause|
|Actual Study Start Date :||September 25, 2018|
|Estimated Primary Completion Date :||December 31, 2020|
|Estimated Study Completion Date :||December 31, 2021|
'Bilateral Oophorectomy Surgery' Group
Premenopausal women planning to undergo a laparoscopic, elective bilateral oophorectomy surgery.
Procedure: Bilateral Oophorectomy Surgery
Women undergoing elective, laparoscopic bilateral oophorectomy surgery will be enrolled.
'Comparative (Control)' Group
Premenopausal women with normal menstrual cycles from a previously completed study at Pennington Biomedical Research Center [NCT01748994] will serve as a comparator (control) group.
- 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 post-surgery ]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.
- Body composition (by Magnetic Resonance Imaging (MRI)) [ Time Frame: Change from baseline in body composition at 8 weeks post-surgery ]Visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and total adipose tissue (TAT) will be assessed by MRI scan (3T GE Discovery 750w).
- 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): NCT03631680
|United States, Louisiana|
|Pennington Biomedical Research Center|
|Baton Rouge, Louisiana, United States, 70808|
|Principal Investigator:||Kara L Marlatt, PhD, MPH||Pennington Biomedical Research Center|