The Role of Estrogen in Adipocyte Remodeling Following Surgical Menopause

NCT03631680 | Terminated

• 1 other identifier: PBRC 2018-022
• Study Type: observational
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

The overarching aim of this study is to assess the downstream effects of abrupt estrogen deficiency in women undergoing elective bilateral oophorectomy by studying:

1. 1.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;
2. 2.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.

Conditions

Menopause Surgical; Estrogen Deficiency; Adiposity

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 post-surgery

Secondary Outcomes (5)

• 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

• Body composition (by Magnetic Resonance Imaging (MRI))

  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 (2)

'Bilateral Oophorectomy Surgery' Group

Premenopausal women planning to undergo a laparoscopic, elective bilateral oophorectomy surgery.

Procedure: Bilateral Oophorectomy Surgery

'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.

Interventions

Bilateral Oophorectomy Surgery PROCEDURE

Women undergoing elective, laparoscopic bilateral oophorectomy surgery will be enrolled.

'Bilateral Oophorectomy Surgery' Group

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: Premenopausal women planning to undergo elective, laparoscopic bilateral oophorectomy surgery.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Healthy women that are planning to undergo elective, laparoscopic bilateral oophorectomy surgery.

You may qualify if:

• Healthy females
• Ages 18-45 y
• BMI between 25 kg/m2 and 40 kg/m2 (±0.5 kg/m2 will be accepted)
• Are pre-menopausal (follicle-stimulating hormone, FSH\<40 mIU/mL)
• Asymptomatic for the following menopause-related symptoms: hot flashes, insomnia (trouble sleeping), or mood swings
• Planning to have a laparoscopically, elective bilateral oophorectomy
• No medical indication for increased cancer risk
• 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:

• Unstable weight in the last 3 months \[gain or loss \>7 lb (or 3.2 kg)\]
• Significant changes in diet or physical activity level within the past month
• Smoking or use of tobacco products within the last 3 months
• Amenorrhea (or absence of regular monthly cycles)
• History of clinically diagnosed diabetes or a fasting blood glucose \>126 mg/dL
• Average screening blood pressure \>140/90 mmHg
• Chronic use of systemic glucocorticoids, systemic adrenergic-stimulating agents, 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
• 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)
• Unable or unwilling to have an MRI performed
• Pregnant, planning to become pregnant, or breastfeeding
• Use of hormone replacement therapy.

Sponsors & Collaborators

• Pennington Biomedical Research Center: lead
• Louisiana Clinical and Translational Science Center: 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

Study Record Dates

• First Submitted: August 9, 2018
• First Posted: August 15, 2018
• Study Start: September 25, 2018
• Primary Completion: November 11, 2022
• Study Completion: November 11, 2022
• Last Updated: November 16, 2022

Record last verified: 2022-11

Locations

US (1)