The Influence of Gonadal Hormone Suppression on Adipocyte Lineage and the Microbiome (BATE Plus)

August 18, 2021 updated by: University of Colorado, Denver
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.

Study Overview

Status

Terminated

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

5

Phase

  • Not Applicable

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

    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Anschutz Medical Campus

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 50 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.

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

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: GnRHag
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.
Ovarian Hormone Suppression - the purpose of the intervention is not to study the drug, but the impact of the loss of ovarian hormones.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Accumulation of Myeloid Cells
Time Frame: 8 months after enrollment of last participant
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
Time Frame: 1 year after completion of last participant
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
Time Frame: 1 year after completion of last participant
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
In Vitro Metabolic Phenotyping
Time Frame: 2 years after completion of last participant
in vitro measurement of lipid and glucose uptake, insulin and adrenergic sensitivity, and mitochondrial content.
2 years after completion of last participant
β-glucuronidase activity
Time Frame: 2 years after completion of last participant
analysis of β-glucuronidase activity in fecal samples from premenopausal women under gonadal hormone suppression therapy via a 96-well assay. This will serve as a direct measure of fecal capacity for estrogen metabolism.
2 years after completion of last participant
Estrogen parent: metabolite ratios
Time Frame: 2 years after completion of last participant
comparison of estrogen parent: metabolite ratios in relation to changes in bacterial diversity and enzyme activity. We will use UPLC-MS/MS metabolomics.
2 years after completion of last participant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Kathleen M Gavin, PhD, University of Colorado, Denver

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)

January 11, 2018

Primary Completion (Actual)

December 18, 2019

Study Completion (Actual)

December 18, 2019

Study Registration Dates

First Submitted

January 5, 2018

First Submitted That Met QC Criteria

January 5, 2018

First Posted (Actual)

January 11, 2018

Study Record Updates

Last Update Posted (Actual)

August 25, 2021

Last Update Submitted That Met QC Criteria

August 18, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Other Study ID Numbers

  • 17-1869

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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.

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