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

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03396978
• Collaborator: (none)
• Enrollment: 5
• Location: 1
• Arm: 1
• Actual Duration (Months): 23.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Adipose Tissue; Microbiome; Menopause	Other: GnRHag	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: The Influence of Gonadal Hormone Suppression on Adipocyte Lineage and the Microbiome
• Actual Study Start Date: Jan 11, 2018
• Actual Primary Completion Date: Dec 18, 2019
• Actual Study Completion Date: Dec 18, 2019

Arms and Interventions

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.

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

Outcome Measures

Primary Outcome Measures

1. Accumulation of Myeloid Cells [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.

2. Progenitor proliferation and adipogenic potential [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.

3. Gut microbial diversity [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

Secondary Outcome Measures

1. In Vitro Metabolic Phenotyping [2 years after completion of last participant]

   in vitro measurement of lipid and glucose uptake, insulin and adrenergic sensitivity, and mitochondrial content.

2. β-glucuronidase activity [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.

3. Estrogen parent: metabolite ratios [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado Anschutz Medical Campus	Aurora	Colorado	United States	80045

Sponsors and Collaborators

• University of Colorado, Denver

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT03396978
• Other Study ID Numbers: 17-1869
• First Posted: Jan 11, 2018
• Last Update Posted: Aug 25, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Study Results

No Results Posted as of Aug 25, 2021