Clinical trial NCT05334888: Sex-differential Host-microbiome CVD Risk - A Longitudinal Cohort Approach
Official title: Sex Hormone-specific Cardiovascular Risks in the Gut Microbiome-host Axis - A Longitudinal Cohort Study.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Transgender
Gut Microbiome
Immune System
Cardiovascular Risk Factors
Keywords: Transgender Medicine
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
First posted: 2022-04-19
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Healthy transgender individuals during their gender hormone replacement therapy (HRT)

Brief summary: The XCVD study investigates the influence of sex hormones on the composition of the gut microbiome and the possible emergence of cardiovascular risk factors. It will follow 200 healthy transgender individuals for two years during their hormone replacement therapy (HRT) and analyze them for the possible emergence of cardiovascular risk factors in relation to changes in the gut microbiome, metabolome, and immunome. We would also like to phenotype cardiovascular disease.

Detailed description: Conducting this innovative study using established scientific methods such as omics platforms, systems biology, and careful CVD phenotyping will allow, for the first time, extensive data collection on the influence of sex hormones on the development of CVD risk factors as well as the role of the gut microbiome. In doing so, the influence of circulating sex hormones can also be quantified to potentially predict CVD risk markers.

Eligibility criteria: Inclusion Criteria:

* Age 18-50
* Language requirements: German, English
* Previous gender hormone replacement therapy (HRT).
* Ability to give consent and written consent to participate.
* Health insurance (for clarification of incidental findings)

Exclusion Criteria:

* Diseases or functional disorders that, in the opinion of the study physician, preclude participation in the study.
* Incapacity or other circumstances that do not allow study participants to fully understand the nature, significance and scope of this study.

Primary outcomes:
measure: Changes in relative species abundance of intestinal bacteria compared
timeFrame: Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
Secondary outcomes:
measure: Changes in cardio marker
timeFrame: Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
measure: Changes in hormone parameters
timeFrame: Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
measure: Changes in immune marker
timeFrame: Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
measure: Changes in the concentration of of cortisol, progesterone, testosterone and dehydroepiandrosterone
timeFrame: Baseline, 2 years Follow Up
measure: Changes in the oral species abundance
timeFrame: Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
measure: Changes in Immune cell marker / regulatory T-cells
timeFrame: Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
measure: Changes in Epigenomics
timeFrame: Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
measure: Changes in Proteomics
timeFrame: Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
measure: Changes in Metabolomics
timeFrame: Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
measure: Changes in relative species abundance of skin microbioma
timeFrame: Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
measure: Changes in BMI
timeFrame: Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
measure: Changes in circumference
timeFrame: Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
measure: Gender identity
timeFrame: Baseline, 6, 12, 18 and 24 months Follow Up
measure: Changes in physical activity
timeFrame: Baseline, 6, 12, 18 and 24 months Follow Up
measure: Changes in mental health
timeFrame: Baseline, 6, 12, 18 and 24 months Follow Up
measure: Changes in Perceived Stress
timeFrame: Baseline, 6, 12, 18 and 24 months Follow Up
measure: Changes in quality of life
timeFrame: Baseline, 6, 12, 18 and 24 months Follow Up
measure: Changes in depression
timeFrame: Baseline, 6, 12, 18 and 24 months Follow Up
measure: Changes in chrono type / sleep-wake behaviour
timeFrame: Baseline, 6, 12, 18 and 24 months Follow Up
measure: Changes in dietary habits
timeFrame: Baseline, 6, 12, 18 and 24 months Follow Up
measure: Changes in socio-demographics
timeFrame: Baseline, 2 years Follow Up
measure: Documentation of HRT
timeFrame: Baseline - HRT start, 6, 12, 18 and 24 months Follow Up
measure: Changes in vital signs
timeFrame: Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
measure: Changes in life style risk parameters
timeFrame: Baseline, 2 years Follow Up
measure: Changes in CVD risk scores
timeFrame: Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Experimental and Clinical Research Center, Clinical Research Unit
Study officials:
affiliation: Max-Delbrück-Center
name: Sofia Forslund, Dr.
role: STUDY_DIRECTOR
affiliation: Charite - Universitätsmedizin Berlin
name: Lajos Marko
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fromentin S, Forslund SK, Chechi K, Aron-Wisnewsky J, Chakaroun R, Nielsen T, Tremaroli V, Ji B, Prifti E, Myridakis A, Chilloux J, Andrikopoulos P, Fan Y, Olanipekun MT, Alves R, Adiouch S, Bar N, Talmor-Barkan Y, Belda E, Caesar R, Coelho LP, Falony G, Fellahi S, Galan P, Galleron N, Helft G, Hoyles L, Isnard R, Le Chatelier E, Julienne H, Olsson L, Pedersen HK, Pons N, Quinquis B, Rouault C, Roume H, Salem JE, Schmidt TSB, Vieira-Silva S, Li P, Zimmermann-Kogadeeva M, Lewinter C, Sondertoft NB, Hansen TH, Gauguier D, Gotze JP, Kober L, Kornowski R, Vestergaard H, Hansen T, Zucker JD, Hercberg S, Letunic I, Backhed F, Oppert JM, Nielsen J, Raes J, Bork P, Stumvoll M, Segal E, Clement K, Dumas ME, Ehrlich SD, Pedersen O. Microbiome and metabolome features of the cardiometabolic disease spectrum. Nat Med. 2022 Feb;28(2):303-314. doi: 10.1038/s41591-022-01688-4. Epub 2022 Feb 17.
citation: Talmor-Barkan Y, Bar N, Shaul AA, Shahaf N, Godneva A, Bussi Y, Lotan-Pompan M, Weinberger A, Shechter A, Chezar-Azerrad C, Arow Z, Hammer Y, Chechi K, Forslund SK, Fromentin S, Dumas ME, Ehrlich SD, Pedersen O, Kornowski R, Segal E. Metabolomic and microbiome profiling reveals personalized risk factors for coronary artery disease. Nat Med. 2022 Feb;28(2):295-302. doi: 10.1038/s41591-022-01686-6. Epub 2022 Feb 17.