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

Menopause Clinical Trial

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Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03396978
• Other study ID #: 17-1869
• Status: Terminated
• Phase: N/A
• Start date: January 11, 2018
• Est. completion date: December 18, 2019

Study information

• Verified date: August 2021
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: December 18, 2019
• Est. primary completion date: December 18, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Adipose Tissue
• Menopause
• Microbiome

Intervention

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.

Locations

Country	Name	City	State
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Denver

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	In Vitro Metabolic Phenotyping	in vitro measurement of lipid and glucose uptake, insulin and adrenergic sensitivity, and mitochondrial content.	2 years after completion of last participant
Secondary	ß-glucuronidase activity	analysis of ß-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
Secondary	Estrogen parent: metabolite ratios	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