- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03631680
The Role of Estrogen in Adipocyte Remodeling Following Surgical Menopause (RESUME)
November 11, 2022 updated by: Kara Marlatt, Pennington Biomedical Research Center
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.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
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.
Study Type
Observational
Enrollment (Actual)
2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Louisiana
-
Baton Rouge, Louisiana, United States, 70808
- Pennington Biomedical Research Center
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 45 years (ADULT)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
Female
Sampling Method
Non-Probability Sample
Study Population
Healthy women that are planning to undergo elective, laparoscopic bilateral oophorectomy surgery.
Description
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).
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
'Bilateral Oophorectomy Surgery' Group
Premenopausal women planning to undergo a laparoscopic, elective 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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Change from baseline in enrichment of DNA of adipose cells with deuterium at 8 weeks post-surgery
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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).
|
Change from baseline in size of adipocytes at 8 weeks post-surgery
|
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.
|
Change from baseline in number of adipocytes at 8 weeks post-surgery
|
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.
|
Change from baseline in body composition at 8 weeks post-surgery
|
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.
|
Changes from baseline in gene and protein expression at 8 weeks post-surgery
|
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).
|
Change from baseline in body composition at 8 weeks post-surgery
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
September 25, 2018
Primary Completion (ACTUAL)
November 11, 2022
Study Completion (ACTUAL)
November 11, 2022
Study Registration Dates
First Submitted
August 9, 2018
First Submitted That Met QC Criteria
August 13, 2018
First Posted (ACTUAL)
August 15, 2018
Study Record Updates
Last Update Posted (ACTUAL)
November 16, 2022
Last Update Submitted That Met QC Criteria
November 11, 2022
Last Verified
November 1, 2022
More Information
Terms related to this study
Other Study ID Numbers
- PBRC 2018-022
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Adiposity
-
Johns Hopkins UniversityCompleted
-
Neothetics, IncCompletedSubcutaneous Abdominal AdiposityUnited States
-
University Hospital, BrestCompleted
-
University of SharjahAl Jalila FoundationCompleted
-
University Hospital, Basel, SwitzerlandRigshospitalet, DenmarkCompletedAdipositySwitzerland
-
University of Colorado, DenverNational Institute on Aging (NIA)Not yet recruitingMenopause | Aging | Adiposity | Estrogen DeficiencyUnited States
-
University of Southern CaliforniaTerminatedAdiposity | Obesity, AbdominalUnited States
-
Erbe Elektromedizin GmbHErbe USA IncorporatedRecruitingObesity | AdiposityUnited States
-
Fudan UniversityInner Mongolia Yili Industrial Group Co., LtdCompletedObesity | AdiposityChina
-
Massachusetts General HospitalCompletedAdiposityUnited States
Clinical Trials on Bilateral Oophorectomy Surgery
-
Ismet HortuCompletedOxidative Stress | Ischemia Reperfusion Injury | OophorectomyTurkey
-
University Medical Center NijmegenActive, not recruitingOvarian Cancer | BRCA1 Gene Mutation | BRCA2 Gene MutationNetherlands
-
University of California, San FranciscoUniversity of Alabama at BirminghamCompleted
-
National Taiwan University HospitalNational Science Council, TaiwanUnknownMenopause, Premature | Hysterectomy | Attitude | Perception | Ovariectomy | Estrogen Replacement TherapyTaiwan
-
NRG OncologyNational Cancer Institute (NCI)RecruitingOvarian CarcinomaUnited States, Korea, Republic of
-
Clinical Center KragujevacCompletedEndometrial Carcinoma Cellular Diagnosis
-
Pennington Biomedical Research CenterUniversity of Colorado, Denver; University of Alabama at BirminghamWithdrawnAdiposity | Hormone Deficiency | Menopause Surgical | Estrogen Deficiency | Follicle-Stimulating Hormone DeficiencyUnited States
-
University Hospital, GasthuisbergFondazione Policlinico Universitario Agostino Gemelli IRCCS; University Medical...RecruitingEndometrial CancerBelgium
-
M.D. Anderson Cancer CenterRecruitingFIGO Grade 1 Endometrial Endometrioid Adenocarcinoma | FIGO Grade 2 Endometrial Endometrioid AdenocarcinomaUnited States
-
University of OklahomaCompleted