The Influence of Gonadal Hormone Suppression on Adipocyte Lineage and the Microbiome (BATE Plus)
18. august 2021 opdateret af: 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.
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
5
Fase
- Ikke anvendelig
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
-
-
Colorado
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Aurora, Colorado, Forenede Stater, 80045
- University of Colorado Anschutz Medical Campus
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Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år til 50 år (Voksen)
Tager imod sunde frivillige
Ja
Køn, der er berettiget til at studere
Kvinde
Beskrivelse
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.
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Grundvidenskab
- Tildeling: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
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Eksperimentel: 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.
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Ovarian Hormone Suppression - the purpose of the intervention is not to study the drug, but the impact of the loss of ovarian hormones.
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Accumulation of Myeloid Cells
Tidsramme: 8 months after enrollment of last participant
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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.
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8 months after enrollment of last participant
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Progenitor proliferation and adipogenic potential
Tidsramme: 1 year after completion of last participant
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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.
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1 year after completion of last participant
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Gut microbial diversity
Tidsramme: 1 year after completion of last participant
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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
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1 year after completion of last participant
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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In Vitro Metabolic Phenotyping
Tidsramme: 2 years after completion of last participant
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in vitro measurement of lipid and glucose uptake, insulin and adrenergic sensitivity, and mitochondrial content.
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2 years after completion of last participant
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β-glucuronidase activity
Tidsramme: 2 years after completion of last participant
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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.
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2 years after completion of last participant
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Estrogen parent: metabolite ratios
Tidsramme: 2 years after completion of last participant
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comparison of estrogen parent: metabolite ratios in relation to changes in bacterial diversity and enzyme activity.
We will use UPLC-MS/MS metabolomics.
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2 years after completion of last participant
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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Efterforskere
- Ledende efterforsker: Kathleen M Gavin, PhD, University of Colorado, Denver
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart (Faktiske)
11. januar 2018
Primær færdiggørelse (Faktiske)
18. december 2019
Studieafslutning (Faktiske)
18. december 2019
Datoer for studieregistrering
Først indsendt
5. januar 2018
Først indsendt, der opfyldte QC-kriterier
5. januar 2018
Først opslået (Faktiske)
11. januar 2018
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
25. august 2021
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
18. august 2021
Sidst verificeret
1. august 2021
Mere information
Begreber relateret til denne undersøgelse
Andre undersøgelses-id-numre
- 17-1869
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
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