Sex-differential Host-microbiome CVD Risk - A Longitudinal Cohort Approach (XCVD)

Sex Hormone-specific Cardiovascular Risks in the Gut Microbiome-host Axis - A Longitudinal Cohort Study.

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.

Study Overview

• Status: Recruiting
• Conditions: Cardiovascular Risk Factors; Gut Microbiome; Transgender; Immune System

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.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Lajos Marko, Dr.; Email: lajos.marko@charite.de
• Study Contact Backup: Name: Sofia Forslund, Prof. Dr.; Phone Number: +49 30 450540649; Email: sofia.forslund@mdc-berlin.de

Study Locations

• Germany
  • Berlin, Germany, 13125
    • Recruiting
    • Experimental and Clinical Research Center, Clinical Research Unit
    • Contact: Michael Boschmann, MD; Phone Number: +4930450540241; Email: michael.boschmann@charite.de
    • Contact: Lajos Marko, MD, PhD; Phone Number: +4930450540144; Email: lajos.marko@charite.de
    • Principal Investigator: Lajos Marko, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Healthy transgender individuals during their gender hormone replacement therapy (HRT)

Description

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.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in relative species abundance of intestinal bacteria compared	baseline and 2 years after initiation of hormone replacement therapy. stool samples: Analysis with 16s rRNA sequencing	Baseline, 2 years Follow Up (optional: after 1 year Follow Up)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in cardio marker	sera: following cardio marker can be determined by Electro Chemiluminescence Immuno-Assay: BNP and hs-troponin.	Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
Changes in hormone parameters	sera: following hormones can be determined by mass spectrometry: Free Androgen Index (fAI), Beta-CrossLaps (BCTX), Carboxy-terminal Propeptide of Procollagen I (P1CP), Luteinizing Hormone, Oestradiol, Progesterone, Testosterone, Free Testosterone, Sex Hormone Binding Globulin, Dihydrotestosterone, Oestron, Free Oestriol.	Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
Changes in immune marker	sera: pro- and anti-inflammatory cytokines using cytokine - multiplex panel and Immune cell populations with shotgun sequencing	Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
Changes in the oral species abundance	saliva sample / oral / mouth: species abundance of oral bacteria (sequencing)	Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
Changes in Proteomics	sera: MS and ELISA	Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
Changes in Metabolomics	sera: MS and ELISA	Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
Changes in relative species abundance of skin microbioma	skin swab: DNA - sequencing	Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
Changes in BMI	body mass index (kg/m²)	Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
Changes in circumference	circumference measurement (cm): waist and hip	Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
Gender identity	questionnaire: Transgender Congruence Scale (TCS) & gender dysphoria	Baseline, 6, 12, 18 and 24 months Follow Up
Changes in physical activity	questionnaire: International Physical Activity Questionnaire / IPAQ	Baseline, 6, 12, 18 and 24 months Follow Up
Changes in mental health	questionnaire: Generalized Anxiety Disorder / GAD-7	Baseline, 6, 12, 18 and 24 months Follow Up
Changes in Perceived Stress	questionnaire: Perceived Stress Questionnaire / PSQ	Baseline, 6, 12, 18 and 24 months Follow Up
Changes in quality of life	questionnaire: quality of life / PROMIS	Baseline, 6, 12, 18 and 24 months Follow Up
Changes in depression	questionnaire: Beck-Depressions-Inventar Revision / BDI II & The Patient Health Questionnaire (PHQ-9)	Baseline, 6, 12, 18 and 24 months Follow Up
Changes in chrono type / sleep-wake behaviour	questionnaire: Munich ChronoType Questionnaire (MCTQ)	Baseline, 6, 12, 18 and 24 months Follow Up
Changes in dietary habits	Food Frequency Quenstionnaire /FFQ, special diet and intake of dietary supplements, prebiotics and probiotics	Baseline, 6, 12, 18 and 24 months Follow Up
Documentation of HRT	HRT medication, dosing, regimes, and progress as well as all transition -relevant surgery and physical changes	Baseline - HRT start, 6, 12, 18 and 24 months Follow Up
Changes in vital signs	Systolic and diastolic blood pressure and heart rate	Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
Changes in socio-demographics	Family status, education level, current working status, and living situation	Baseline, 2 years Follow Up
Changes in the concentration of of cortisol, progesterone, testosterone and dehydroepiandrosterone	Hair sample: Hair steroid analysis with Immunoassay and LC-MS/MS	Baseline, 2 years Follow Up
Changes in Immune cell marker / regulatory T-cells	Whole blood samples for Immune cell populations and peripheral blood mononuclear cells RNA isolation for whole-transcriptome shotgun sequencing.	Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
Changes in Epigenomics	Whole blood samples for Immune cell populations and peripheral blood mononuclear cells RNA isolation for whole-transcriptome shotgun sequencing.	Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
Changes in life style risk parameters	Smoking status, alcohol consumption and use of recreational drugs	Baseline, 2 years Follow Up
Changes in CVD risk scores	Framingham risk scores (FRS) and Systematic Coronary Risk Evaluation (SCORE)	Baseline, 2 years Follow Up (optional: after 1 year Follow Up)

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
• Investigators: Study Director: Sofia Forslund, Dr., Max-Delbrück-Center; Principal Investigator: Lajos Marko, Charité - Universitätsmedizin Berlin

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Short proposal of the study

Study record dates

Study Major Dates

• Study Start (Actual): August 29, 2022
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: April 4, 2022
• First Submitted That Met QC Criteria: April 13, 2022
• First Posted (Actual): April 19, 2022

Study Record Updates

• Last Update Posted (Estimated): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 8, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Transgender Medicine
• Other Study ID Numbers: ChariteU - ECRC XCVD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No