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The Role of Estrogen in Adipocyte Remodeling Following Surgical Menopause (RESUME)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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
Sponsor:
Collaborator:
Louisiana Clinical and Translational Science Center
Information provided by (Responsible Party):
Kara Marlatt, Pennington Biomedical Research Center

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. 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. 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

Detailed Description:
This is a cross-sectional study that will enroll up to 10 women undergoing laparoscopic, elective bilateral oophorectomy at a local hospital in Baton Rouge, LA. Women will complete 7 study visits over 3 months; a single screening visit to assess eligibility, a pre-bilateral oophorectomy visit for imaging and adipose tissue biopsy collection, and 5 post-bilateral oophorectomy visits to "dose", maintain compliance and subject retention, and perform follow-up imaging and adipose tissue biopsy collection for outcome measures.

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Study Type : Observational
Estimated Enrollment : 10 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Menopause

Group/Cohort Intervention/treatment
'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.



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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).

  2. 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.

  3. 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.

  4. 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).

  5. 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
Adipose tissue


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Premenopausal women planning to undergo elective, laparoscopic bilateral oophorectomy surgery.
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Healthy women that are planning to undergo elective, laparoscopic bilateral oophorectomy surgery.
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.
  • 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).

Information from the National Library of Medicine

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


Locations
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United States, Louisiana
Pennington Biomedical Research Center
Baton Rouge, Louisiana, United States, 70808
Sponsors and Collaborators
Pennington Biomedical Research Center
Louisiana Clinical and Translational Science Center
Investigators
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Principal Investigator: Kara L Marlatt, PhD, MPH Pennington Biomedical Research Center
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Responsible Party: Kara Marlatt, Postdoctoral Researcher, Pennington Biomedical Research Center
ClinicalTrials.gov Identifier: NCT03631680    
Other Study ID Numbers: PBRC 2018-022
First Posted: August 15, 2018    Key Record Dates
Last Update Posted: May 20, 2020
Last Verified: May 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No