Sex-differential Host-microbiome CVD Risk - A Longitudinal Cohort Approach

Cardiovascular Risk Factors Clinical Trial

— XCVD  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05334888
• Other study ID #: ChariteU - ECRC XCVD
• Status: Recruiting
• Start date: August 29, 2022
• Est. completion date: December 31, 2027

Study information

• Verified date: February 2024
• Source: Charite University, Berlin, Germany
• Contact: Sofia Forslund, Prof. Dr.
• Phone: +49 30 450540649
• Email: sofia.forslund[@]mdc-berlin.de
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 31, 2027
• Est. primary completion date: December 31, 2025
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cardiovascular Risk Factors
• Gut Microbiome
• Immune System
• Transgender

Locations

Country	Name	City	State
Germany	Experimental and Clinical Research Center, Clinical Research Unit	Berlin

Sponsors (2)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany	Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)

Country where clinical trial is conducted

Germany, 

References & Publications (2)

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, — View 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 micro — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Changes in Proteomics	sera: MS and ELISA	Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
Secondary	Changes in Metabolomics	sera: MS and ELISA	Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
Secondary	Changes in relative species abundance of skin microbioma	skin swab: DNA - sequencing	Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
Secondary	Changes in BMI	body mass index (kg/m²)	Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
Secondary	Changes in circumference	circumference measurement (cm): waist and hip	Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
Secondary	Gender identity	questionnaire: Transgender Congruence Scale (TCS) & gender dysphoria	Baseline, 6, 12, 18 and 24 months Follow Up
Secondary	Changes in physical activity	questionnaire: International Physical Activity Questionnaire / IPAQ	Baseline, 6, 12, 18 and 24 months Follow Up
Secondary	Changes in mental health	questionnaire: Generalized Anxiety Disorder / GAD-7	Baseline, 6, 12, 18 and 24 months Follow Up
Secondary	Changes in Perceived Stress	questionnaire: Perceived Stress Questionnaire / PSQ	Baseline, 6, 12, 18 and 24 months Follow Up
Secondary	Changes in quality of life	questionnaire: quality of life / PROMIS	Baseline, 6, 12, 18 and 24 months Follow Up
Secondary	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
Secondary	Changes in chrono type / sleep-wake behaviour	questionnaire: Munich ChronoType Questionnaire (MCTQ)	Baseline, 6, 12, 18 and 24 months Follow Up
Secondary	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
Secondary	Changes in socio-demographics	Family status, education level, current working status, and living situation	Baseline, 2 years Follow Up
Secondary	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
Secondary	Changes in vital signs	Systolic and diastolic blood pressure and heart rate	Baseline, 2 years Follow Up (optional: after 1 year Follow Up)
Secondary	Changes in life style risk parameters	Smoking status, alcohol consumption and use of recreational drugs	Baseline, 2 years Follow Up
Secondary	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)

External Links

•   Short proposal of the study