NCT03396978

Brief Summary

This research study plans to learn more about the role of female sex hormones on adipose tissue (or fat) and the gut microbiome (or the organisms that are in your digestive tract). The rationale for this study is that the rate at which women gain fat (especially in the stomach region) increases after menopause. It is thought to be due to the loss of estrogen because post-menopausal women who take estrogen gain less weight than those who do not take estrogen. Gut bacteria process estrogen and help determine the types of estrogen that circulate in the body. These bacteria can be changed with lifestyle factors such as diet, and may therefore, also affect the risk of diseases that are more common in women after menopause i.e., cardiovascular disease and cancer. In this study the investigators will obtain fat biopsies before and after 6 months of ovarian hormone suppression to measure how the fat cells change with the loss of female sex hormones (e.g., medical menopause). The investigators will also obtain stool and urine samples before and every month during the study to measure changes in the microbiome.

Trial Health

57
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Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
5

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Jan 2018

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 5, 2018

Completed
6 days until next milestone

First Posted

Study publicly available on registry

January 11, 2018

Completed
Same day until next milestone

Study Start

First participant enrolled

January 11, 2018

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 18, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 18, 2019

Completed
Last Updated

August 25, 2021

Status Verified

August 1, 2021

Enrollment Period

1.9 years

First QC Date

January 5, 2018

Last Update Submit

August 18, 2021

Conditions

Adipose TissueMicrobiomeMenopause

Outcome Measures

Primary Outcomes (3)

  • Accumulation of Myeloid Cells

    Quantification of accumulation of myeloid cells in abdominal subcutaneous adipose tissue of women before and after gonadal hormone suppression as assessed by CD45+/CD14+ staining via flow cytometry of isolated adipose stroma.

    8 months after enrollment of last participant

  • Progenitor proliferation and adipogenic potential

    Progenitor proliferation measured by BrdU and adipogenic potential as measured by Oil Red-O staining with quantification by absorbance. Adipocyte specific gene/protein expression will be measured to confirm adipocyte status.

    1 year after completion of last participant

  • Gut microbial diversity

    Comparison of gut microbial diversity before and after gonadal hormone suppression at monthly intervals as assessed by sequencing of the V4 region of 16s rRNA

    1 year after completion of last participant

Secondary Outcomes (3)

  • In Vitro Metabolic Phenotyping

    2 years after completion of last participant

  • β-glucuronidase activity

    2 years after completion of last participant

  • Estrogen parent: metabolite ratios

    2 years after completion of last participant

Study Arms (1)

GnRHag

EXPERIMENTAL

Participants will undergo 6 months of gonadotropin releasing hormone agonist (GnRHag) therapy (intramuscular injection of leuprolide acetate 3.75 mg for depot suspension; Lupron; TAP Pharmaceutical Products, Inc.; Lake Forest, IL) to chronically suppress ovarian hormones. A single injection of leuprolide acetate produces an initial stimulation (for up to 3 wk) followed by a prolonged suppression of pituitary gonadotropins and ovarian hormones. Repeated monthly dosing suppresses ovarian hormone secretion.

Other: GnRHag

Interventions

GnRHagOTHER

Ovarian Hormone Suppression - the purpose of the intervention is not to study the drug, but the impact of the loss of ovarian hormones.

GnRHag

Eligibility Criteria

Age18 Years - 50 Years
Sexfemale(Gender-based eligibility)
Gender Eligibility DetailsMust be biological female. This study is investigating ovarian hormone suppression.
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Enrollment into the parent protocol (COMIRB 16-1479 - The impact of estrogen status on the biological function of brown adipose tissue in women measured using quantitative PET/CT; PI - Edward Melanson, PhD)
  • Participation in GnRHag intervention

You may not qualify if:

  • Known allergy to lidocaine or other numbing medication
  • Uncontrolled bleeding disorder or inability to withhold aspirin/NSAIDs or other blood thinning medications for 7 days prior to biopsy procedure.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Study Officials

  • Kathleen M Gavin, PhD

    University of Colorado, Denver

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 5, 2018

First Posted

January 11, 2018

Study Start

January 11, 2018

Primary Completion

December 18, 2019

Study Completion

December 18, 2019

Last Updated

August 25, 2021

Record last verified: 2021-08

Data Sharing

IPD Sharing
Will not share

Locations

US(1)