Protocol TRANS and QT Repolarization

QTc Interval Clinical Trial

— QTrans  

Official title:

Analysis of Ventricular Repolarization by QT Measurement in Transgender People Treated With Hormone Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05865262
• Other study ID #: 2021.11.16_Grouthier
• Status: Completed
• Start date: November 16, 2021
• Est. completion date: January 1, 2023

Study information

• Verified date: April 2024
• Source: University Hospital, Bordeaux
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The consequence of hormone-based treatment on cardiac electrophysiology in transgender individuals is poorly explored. We will investigate the effects of gender affirming hormone treatments on ventricular repolarization (ie. QTc, QT corrected for heart rate duration) in a prospective cohort of transgender individuals before and after feminizing and masculinizing treatments, and transversally in transgender individuals on gender affirming hormone treatments. This monocentric cohort will be included in the Endocrinology department of the Haut-Leveque Hospital in Pessac (France).

Description:

An essential step in the care of gender dysphoria is gender-affirming hormone therapy (GAHT) combining an anti-androgen and estrogen therapy in transgender women (formerly male to female) or androgen therapy in transgender men (female to male). Several studies have shown a detrimental effect of GAHT on cardiovascular risk factors and therefore, the European Society of Endocrinology recommend an enhanced monitoring of cardiovascular risk factors in transgender population. Data on the risk of cardiac arrhythmias in transgender population are lacking, particularly on ventricular repolarization and QTc. Indeed, sex steroid hormones and gonadotropins are known to alter the cardiac electrophysiology, as shown in various animal and human studies. From puberty to menopause, the QTc is generally longer in women than in men, translating into a higher risk of Torsade de Pointes (a peculiar form of ventricular arrhythmia) in women versus men. Recent publications have well illustrated the shortening of QTc in women in situation of biological hyperandrogenism and; QTc lengthening in hypogonadal men which was reversed by restoration of physiological eugonadal testosterone levels. Gonadotrophin's levels were positively correlated with QTc. To date, no study has focused on changes in cardiac repolarization in the transgender population and particularly on the effects of GAHT. The aim of this study is to evaluate the impact of feminizing and masculinizing hormone treatments (GAHT) on ventricular repolarization (i.e QTc) in transgender individuals, followed at the Endocrinology department of the Haut-Leveque hospital in Pessac. We aim to enroll consecutively (monocentric cohort) transgender individuals (on and before treatment) consulting to the endocrinology department for their usual standard of care follow-up until we include 15 transgender men and 15 transgender women with 2 QTc assessments available, one before and the other after initiation of GAHT (triplicates of 10 sec ECGs, Fridericia's heart rate correction for each time-point). This effective (n=15/group) have ≥85% power to detect a difference in QTcF≥10msec between the ECG before and after initiation of GAHT with a paired t-test (α: 0.05; standard deviation of QTc in each subgroup: 12msec; expected QTcF mean: 410msec and 400msec in women and men before GAHT, respectively, intra-individual correlation: 0.5).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: January 1, 2023
• Est. primary completion date: November 16, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Individuals with gender dysphoria consulting as part of the usual standard of care follow-up in endocrinology for instauration of the follow-up of GAHT

Exclusion Criteria:

• <18 years old
• patients under protective measures or deprived of liberty (under guardianship, curatorship, safeguard of justice, incarcerated)
• history of congenital long QT syndrome

Related Conditions & MeSH terms

• QTc Interval

Intervention

Diagnostic Test:
• ECG
A triplicate ECG and a blood test will be done during a medical consultation as part of the usual endocrinology follow-up. Included individuals seen prior to initiation of GAHT, will be assessed a second time (at least one month after GAHT start) with a triplicate ECG and a blood test similar to inclusion visit. Included individuals already on GAHT will be seen only once at the inclusion visit. Triplicates of 10seconds 12-lead digitized electrocardiogram will be recorded after few minutes of rest in the supine position. Electrocardiograms will be acquired with Mindray ECG BeneHeart R12. For each subject, RR, PR, QRS and QT interval durations will be assessed with a semiautomatic approach using the median representative beats (overlap method) generated from 10seconds ECG with a good quality (CalECG v3.7; AMPS, LLC). The QT interval will be measured and corrected for heart rate by Fridericia's formula.
• blood test (assessing ionic and hormonal circulating levels)
Blood samples for the determination of serum concentrations of estradiol, progesterone, testosterone, FSH, and LH will be collected on the same day as the ECG, in a dry tube and further assayed in the immunology laboratory of Bordeaux University Hospital (France). Estradiol, progesterone, FSH, and LH plasma concentrations will be assayed by immunochemiluminescence (Architect i2000SR; Roche Diagnostics), and testosterone levels by liquid chromatography mass spectrometry. Kalemia and calcemia will be collected in a BD Vacutainer tube with heparin lithium and separator, further assayed at the biochemistry laboratory of Bordeaux University Hospital by indirect potentiometric measurement (Architect c16000) and Arsenazo III SRM 956 colorimetrie (Architect c16000).

Locations

Country	Name	City	State
France	University Hospital Bordeaux, France	Pessac

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Bordeaux	APHP

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess the impact of GAHT on QTc duration in transgender individuals before and after starting therapy	Difference in QTc duration before and after initiation of GAHT	assessments at inclusion and during follow-up visit in endocrinology department (minimum 1 month and max 2 years after treatment started)
Secondary	To assess the difference in PR, QRS, RR, QTc duration between men and women prior to GAHT, and transmen and transwomen already on GAHT.	Difference in PR, QRS, RR, QT, QTc duration on digital ECG at initial inclusion visit between men and women prior to GAHT, and transmen and transwomen already on GAHT	assessments at inclusion and during follow-up visit in endocrinology department (minimum 1 month and max 2 years after treatment started)
Secondary	To assess the impact of gender-affirming hormone treatment on PR, QRS, RR duration in transgender individuals before and after starting GAHT	Difference in PR, QRS, RR duration before and after initiation of GAHT.	assessments at inclusion and during follow-up visit in endocrinology department (minimum 1 month and max 2 years after treatment started)
Secondary	To assess the association between the hormonal and ionic levels with PR, QRS, RR, QTc duration in transgender individuals before and on GAHT.	Correlation (univariate and multivariate, including mixed effects models) between PR, QRS, RR, QTc duration and hormonal (progesterone, testosterone, FSH, LH, estradiol) and ionic (potassium, calcium) circulating levels	assessments at inclusion and during follow-up visit in endocrinology department (minimum 1 month and max 2 years after treatment started)