Understanding the Roles of Hormones in Adipocyte Remodeling Following Menopause

NCT03856268 | Withdrawn

• 1 other identifier: PBRC 2019-010
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The overarching aims of this study are to:

1. 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. 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).

Conditions

Menopause Surgical; Estrogen Deficiency; Adiposity; Follicle-Stimulating Hormone Deficiency; Hormone Deficiency

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Size of adipocytes

  Change from baseline in size of adipocytes at 8 weeks post-surgery

• Number of adipocytes

  Change from baseline in number of adipocytes at 8 weeks post-surgery

• Body composition (by Dual-energy X-ray Absorptiometry (DXA))

  Change from baseline in body composition at 8 weeks post-surgery

• Adipose tissue gene and protein expression

  Changes from baseline in gene and protein expression at 8 weeks post-surgery

Study Arms (3)

ARM 1: 'Surgical Menopause' Group

Premenopausal women having an oophorectomy.

Procedure: 'Surgical Menopause' Group

ARM 2: "Drug-Induced Menopause'

Premenopausal women with gonadal suppression

Drug: 'Drug-Induced Menopause' Group

'Comparative (Control)' Group

Premenopausal women with regular cycles.

Interventions

'Surgical Menopause' Group PROCEDURE

Women undergoing laparoscopic oophorectomy surgery ('surgical menopause') will be enrolled at Pennington Biomedical.

Also known as: 'Bilateral Oophorectomy Surgery' Group

ARM 1: 'Surgical Menopause' Group

'Drug-Induced Menopause' Group DRUG

Women undergoing gonadal suppression via leuprolide acetate (Lupron \[AbbVie Inc.\]) will be enrolled at the University of Colorado-Denver.

Also known as: 'Pharmacology-Induced Menopause' Group

ARM 2: "Drug-Induced Menopause'

Eligibility Criteria

• Age: 18 Years - 50 Years
• Gender Eligibility Details: Premenopausal women planning to undergo elective, laparoscopic bilateral oophorectomy surgery OR gonadal suppression via leuprolide acetate (Lupron \[AbbVie Inc.\]).
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pennington Biomedical Research Center: lead
• University of Colorado, Denver: collaborator
• University of Alabama at Birmingham: collaborator

Study Sites (1)

Pennington Biomedical Research Center

Baton Rouge, Louisiana, 70808, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Adipose tissue

MeSH Terms

Conditions

Obesity

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Kara L Marlatt, PhD, MPH

  Pennington Biomedical Research Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Postdoctoral Researcher - John S McIlhenny Skeletal Muscle Physiology - Ravussin

Study Record Dates

• First Submitted: February 25, 2019
• First Posted: February 27, 2019
• Study Start: April 1, 2019
• Primary Completion: November 11, 2022
• Study Completion: November 11, 2022
• Last Updated: November 16, 2022

Record last verified: 2022-11

Locations

US (1)