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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Transgender, Gut Microbiome, Immune System, Cardiovascular Risk Factors

Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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What is the study measuring?
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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 concentration of cortisol | Hair sample: Hair steroid analysis with Immunoassay and LC-MS/MS | 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 Transcriptomics | Capillary blood sample for Immune cell populations: RNA isolation for whole-transcriptome shotgun 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 | 
| Changes in socio-demographics | Family status, education level, current working status, and living situation | Baseline, 2 years 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 Risk parameters | Smoking status, alcohol consumption and use of recreational drugs | Baseline, 2 years Follow Up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transgender Medicine