Clinical trial NCT03631680: The Role of Estrogen in Adipocyte Remodeling Following Surgical Menopause
Official title: The Role of Estrogen in Adipocyte Remodeling Following Surgical Menopause
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Menopause Surgical
Estrogen Deficiency
Adiposity
Lead sponsor: Pennington Biomedical Research Center
Sponsor class: OTHER
Collaborators: name: Louisiana Clinical and Translational Science Center
First posted: 2018-08-15
Enrollment: 2
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Healthy women that are planning to undergo elective, laparoscopic bilateral oophorectomy surgery.

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.

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.

Eligibility 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).

Primary outcomes:
measure: Rate of in vivo adipogenesis (via deuterium-enrichment of adipose tissue DNA)
timeFrame: Change from baseline in enrichment of DNA of adipose cells with deuterium at 8 weeks post-surgery
Secondary outcomes:
measure: Size of adipocytes
timeFrame: Change from baseline in size of adipocytes at 8 weeks post-surgery
measure: Number of adipocytes
timeFrame: Change from baseline in number of adipocytes at 8 weeks post-surgery
measure: Body composition (by Dual-energy X-ray Absorptiometry (DXA))
timeFrame: Change from baseline in body composition at 8 weeks post-surgery
measure: Body composition (by Magnetic Resonance Imaging (MRI))
timeFrame: Change from baseline in body composition at 8 weeks post-surgery
measure: Adipose tissue gene and protein expression
timeFrame: Changes from baseline in gene and protein expression at 8 weeks post-surgery
Other outcomes:
Locations:
city: Baton Rouge
country: United States
facility: Pennington Biomedical Research Center
state: Louisiana
Study officials:
affiliation: Pennington Biomedical Research Center
name: Kara L Marlatt, PhD, MPH
role: PRINCIPAL_INVESTIGATOR
References: