Understanding the Roles of Hormones in Adipocyte Remodeling Following Menopause

Adiposity Clinical Trial

— RESUME-2  

Official title:

Understanding the Roles of Estradiol and Follicle-stimulating Hormone in Adipocyte Remodeling Following Surgical and Pharmacology-induced Menopause (RESUME-2 Study)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03856268
• Other study ID #: PBRC 2019-010
• Status: Withdrawn
• Start date: April 1, 2019
• Est. completion date: November 11, 2022

Study information

• Verified date: November 2022
• Source: Pennington Biomedical Research Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 11, 2022
• Est. primary completion date: November 11, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Adiposity
• Endocrine System Diseases
• Estrogen Deficiency
• Follicle-Stimulating Hormone Deficiency
• Hormone Deficiency
• Menopause Surgical

Intervention

Procedure:
• 'Surgical Menopause' Group
Women undergoing laparoscopic oophorectomy surgery ('surgical menopause') will be enrolled at Pennington Biomedical.

Drug:
• 'Drug-Induced Menopause' Group
Women undergoing gonadal suppression via leuprolide acetate (Lupron [AbbVie Inc.]) will be enrolled at the University of Colorado-Denver.

Locations

Country	Name	City	State
United States	Pennington Biomedical Research Center	Baton Rouge	Louisiana

Sponsors (3)

Lead Sponsor	Collaborator
Pennington Biomedical Research Center	University of Alabama at Birmingham, University of Colorado, Denver

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of in vivo adipogenesis (via deuterium-enrichment of adipose tissue DNA)	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.	Change from baseline in enrichment of DNA of adipose cells with deuterium at 8 weeks
Secondary	Size of adipocytes	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).	Change from baseline in size of adipocytes at 8 weeks post-surgery
Secondary	Number of adipocytes	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.	Change from baseline in number of adipocytes at 8 weeks post-surgery
Secondary	Body composition (by Dual-energy X-ray Absorptiometry (DXA))	Fat mass, fat-free mass, and percent body fat will be assessed using a whole-body scanner GE iDXA.	Change from baseline in body composition at 8 weeks post-surgery
Secondary	Adipose tissue gene and protein expression	Expression levels of genes and proteins involved in adipocyte expansion and function (ERa, PPAR?2, C/EBPa, aromatase, adiponectin, and LPL), extracellular matrix remodeling and fibrosis (COL6(a1, a2, a3), COL4a1, and TGFß), and inflammation (IL-6 and TNFa) will be assessed.	Changes from baseline in gene and protein expression at 8 weeks post-surgery