Evaluation of the Effectiveness of Hormonal Treatment in Adolescents Suffering From Gender Dysphoria

Phase 3RecruitingNCT06351501

Assistance Publique - Hôpitaux de Paris60 enrolled

Overview

Gender dysphoria (GD) is a significant suffering lasting more than 6 months in a subject, with regard to the discrepancy felt between his or her gender identity and his or her birth sex. From the onset of puberty, most of these self-identified transgender adolescents will persist in their transgender identity and will undergo hormonal and surgical reassignment when the time comes. International best practice guidelines recommend early treatment from the start of pubertal development to block pubertal progression, with the possibility of hormonal transition by administering sex hormones of the desired sex usually around the age of 15.5. However, in order to reduce the psychosocial consequences of GD, more and more referral teams are carrying out this transition from the age of 13.5, although no study has been published to show its benefit compared with a transition at the age of 15.5. In the absence of treatment, co-morbidity among adolescents suffering from gender dysphoria is very high, with anxiety-depressive states, suicidal risk and dropping out of school in the forefront. Our hypothesis is that hormonal transition started at an age closer to physiological puberty can significantly reduce this comorbidity and improve quality of life for these adolescents. This is the first therapeutic trial to be conducted in France in the transgender adolescent population, in an area where international recommendations based on the principles of Evidence Based Medicine are essentially derived from the clinical expertise of teams who have specialized in the care of transgender people for over forty years, while clinical data derived from structured research are still very scarce. The results of this study will guide the care of transgender adolescents, allowing them, if the study is positive, to access hormonal treatments earlier and thus more quickly improve their overall functioning, anxiety-depressive symptoms and their quality of life.

Multicenter, controlled, randomized, open trial with blinded evaluation of the primary endpoint (Prospective Open Blinding Endpoint PROBE study). Randomization will be stratified by sex assigned at birth and the investigating center. The primary analysis will be intention-to-treat and multiple imputation methods will be used to handle missing data. After verification of the inclusion criteria by the child psychiatrist (selection visit), then the pediatric endocrinologist (inclusion visit), the adolescent will be included in the study and will benefit from an initial evaluation (T0) by a psychologist trained for the primary criterion (CGAS) and secondary psycho-affective criteria.The patients will then be sent again to the pediatric endocrinologist who will randomize the patient (via an IT platform) and give them the treatment corresponding to their assigned group. Adolescents in both groups will be reassessed at 15.5 years +/- 6 months (T1). At the end of this evaluation, patients in the control group will begin their hormonal treatment. Adolescents will undergo a final evaluation at 17.5 years +/- 6 months (T2), at which time the same criteria as at T0 and T1 will be collected. Main objective: To evaluate, in gender dysphoric adolescents, having completed their social transition, having or not undergone prior pubertal suppression, the effectiveness of hormonal treatment with estrogens or testosterone initiated at 13.5 years +/- 6 months of age on the overall functioning of the teenager at 15.5 years +/- 6 months old. Primary endpoint: Children's Global Assesment Scale (CGAS) score at age 15.5 +/- 6 months Secondary objectives : Evaluate, in gender dysphoric adolescents who have completed their social transition, whether or not they have benefited from prior pubertal suppression: * the effectiveness of hormonal treatment started at 13.5 years old +/- 6 months vs. 15.5 years old +/- 6 months on the overall functioning of the adolescent at 17.5 years old+/- 6 months, * the safety (side effects) of hormonal treatment started at age 13.5 +/- 6 months, * and the relevance of hormonal treatment started at 13.5 years old +/- 6 months on other parameters assessed at 15.5 +/- 6 months and 17.5 +/- 6 months years old (gender identity, depression, anxiety, emotional, behavioral disorders and other comorbidities, objective and subjective quality of life, body image, height, waist/hip ratio, bone mineral density, BMI).

Eligibility

Sex: ALLMin age: 156 MonthsMax age: 168 Months

Medical Language ↔ Plain English

Inclusion Criteria: * Adolescents aged 13.5 years +/- 6 months, * Having initiated puberty: tanner score ≥2 for transgender boys; tanner score ≥2 for ; (clinic and/or testosterone \>0.3 ng/mL) for transgender girls * Presenting the criteria for gender dysphoria according to the DSM5 assessed by at least two child psychiatric interviews at least six months apart where the diagnosis of gender dysphoria was clinically established and that of associated autism spectrum disorder refuted and/or associated cognitive impairment, confirmed by specific scales (Gender Identity / Gender Dysphoria Questionnaire for Adults and Adolescents (GIDYQ-AA) and Utrecht Gender Dysphoria Scale (UGDS)) * Whose indication for hormonal transition has been validated in a multidisciplinary consultation meeting after at least one consultation with the pediatric endocrinologist with clinical examination, blood pressure measurement, and information on hormonal treatments in the context of gender dysphoria. Exclusion Criteria: * Contraindication to hormonal treatment (see paragraph 1.5) * Hormonal treatment needs to be adjusted (transgender boys patients treated with anti-coagulants or with thrombophilia). * Patients with risk of aggravation of certain diseases under oestrogen treatment (transgender girls patients with uncontrolled diabetes with HBA1C \> 8%, patients with cholelithiasis, biliary lithiasis, systemic lupus erythematosus, severe asthma, severe arterial hypertension, severe migraines, otosclerosis, epilepsy not controlled by treatment). * Patients with cancer with a risk of hypercalcemia (and associated hypercalciuria), linked to bone metastases. * Severe cardiac, hepatic or renal failure or ischemic heart disease, due to the risk of severe complications characterized by edema, with or without congestive heart failure. * Uncontrolled high blood pressure. * Patients with epilepsy and migraine. * Patients with current or history of thromboembolic events. * Severe untreated chronic depression clinically assessed and documented using the Beck Depression Inventory (BDI). * Diagnosed schizophrenia that is unstable or progressive * Diagnosed bipolar disorder that is unstable or progressive * Suicidal ideation identified through the MINI with a Columbia C-SSRS score \> 4, until the clinical condition has stabilized * Current anticoagulant treatment * Severe autism Spectrum Disorder (clinical screening, confirmed in cases of doubt by the Social Responsiveness Scale (SRS) Raw-score \> 76, carried out as part of usual care in cases of clinical evidence, * Cognitive deficit (clinical screening, confirmed by an QI \< 80 on the Weschler scale (WISC V), carried out as part of the usual treatment in the event of clinical evidence. * Refusal to participate in the study on the part of the adolescent or one of the holders of parental authority (both holders and the adolescent must sign a written consent after receiving appropriate information). * No social security cover * Participation in other intervention research * Pregnancy in progress * Insufficient knowledge of French

Outcomes

Primary Outcomes

Global functionning using the Children's Global Assessment Scale (CGAS)

The Children's Global Assessment Scale (CGAS), adapted from the Global Assessment Scale for adults, is a rating of general functioning for children and young people until 16 years old. The clinician assesses a range of aspects of psychological and social functioning and gives the child or young person a single score between 1 and 100, based on their lowest level of functioning. The score puts them in one of ten categories that range from "needs constant supervision" (1-10) to "superior functioning" (91-100). The measure can be used by clinicians as well as researchers to complement other scales measuring more specific symptoms.

Time frame: 15.5 years old +/- 6 months

Secondary Outcomes

Drug use (DEP-ADO)

Drug use: assessed by specific questions via the DEP-ADO questionnaire (screening grid for problem substance use among adolescents). Dep-Ado is a 15 minutes questionnaire to evaluate alcohol and substance use adolescent population aged 12 to 17 years. No problem if total score \<12; warning of \>12 et \<19; pathological use needing intervention if \>20

Time frame: T0 (13.5 years old +/-6 months); T1 (15.5 years old+/-6 months); T2 ( 17.5 years old +/-6 months)

WISC-V (weschler Test)

cognitive test with 4 subscales (verbal comprehension index, perceptual reasoning index, logical score, working memory index, processing speed index). IQ is calculated. If \<80, it is an non inclusion criteria. Normal range between 80 and 120. when \> 120 précocity

Time frame: T0 (13.5 years old +/-6 months); T2 ( 17.5 years old +/-6 months)

UGDS (Utrecht Gender Dysphoria Scale ) and GIDYQ-AA (Gender Identity/ Gender Dysphoria Questionnaire for Adolescents and Adults scale )

The Utrecht Gender Dysphoria Scale (UGDS) is a validated, 12-item screening measure for both adults and adolescents used extensively in gender clinics to assess gender dysphoria. Minimal score= 12; max=60. two versions (AFAB, AMAB)

Time frame: selection visit ; T1 (15.5 years old +/-6 months) ; T2 (17.5 years old +/-6 months)

Beck Depression Inventory (BDI)

is a 21-question multiple-choice self-report inventory, one of the most widely used psychometric tests for measuring the severity of depression.Min = 0 Max = 39 Between 0 and 3 = no Dépression

Time frame: T0 (13.5 years old +/-6 mois); T1 (15.5 years old+/-6 monhs); T2 ( 17.5 years old +/-6 months)

Body Image Scale (BIS)

The 10-item BIS was developed to assess changes in body image assessed with a four-point scale from "not at all" to "very much." High scores indicate higher body image.(Min=30, Max=150 )

Time frame: T0 (13.5 years old +/-6 months); T1 (15.5 years old+/-6 months); T2 ( 17.5 years old +/-6 months)

State and Anxiety Inventory for Children (STAI-C)

STAI-C includes 20-items that describe anxiety experiences a person might experience (e.g., item 6-"I worry too much"©). For each item, participants choose one of three options that indicate how often they experience the described situation - "hardly-ever", "sometimes" or "often"; these options are scored with 1, 2, and 3 points, respectively (total score range: 20-60). Higher scores indicate higher anxiety

Time frame: T0 (13.5 years old +/-6 mois); T1 (15.5 years old+/-6 monhs); T2 ( 17.5 years old +/-6 months)

World Health Organization Quality Of Life - BREF (WHOQOL-BREF)

This 26-item instrument measures four fields, i.e. physical health, mental health, social relations and the environment. The analysis is based on the scores generated for each field (no overall score can be calculated). The user manual is comprehensive, which makes the instrument easy to use (WHO, 1996). While some studies call into question the construct validity (D'Abundo et al., 2011), the WHOQOL-BREF is generally recognized as a reliable, valid instrument to assess quality of life and is widely used in the literature for clinical and population-based surveys (Oliveira, Carvalho and Esteves, 2016; Skevington, Lotfy and O'Connell, 2004).

Time frame: T0 (13.5 years old +/-6 months); T1 (15.5 years old+/-6 months); T2 ( 17.5 years old +/-6 months)

Satisfaction With Life Scale (SWLS)

The SWLS is a short 5-item instrument designed to measure global cognitive judgments of satisfaction with one's life. The scale usually requires only about one minute of a respondent's time.Min=5, Max=35. The higher score means a greater satisfaction with life

Time frame: T0 (13.5 years old +/-6 months); T1 (15.5 years old+/-6 months); T2 ( 17.5 years old +/-6 months)

Height, bone mineral density, BMI, waist to hip ratio

MI is a measurement of a person's leanness or corpulence based on their height and weight, and is intended to quantify tissue mass

Time frame: inclusion visit (13.5 years old +/-6 months); T1 (15.5 years old+/-6 months); T2 ( 17.5 years old +/-6 months)

Mini International Neuropsychiatric Interview (MINI)

To assess the 17 most common psychiatric disorders and suicidality in DSM-III-R, DSM-IV and DSM-5 and ICD-10. The MINI was designed as a brief structured diagnostic interview to meet the need for a short but accurate structured psychiatric interview for multicenter clinical trials and epidemiology studies and to be used as a first step in outcome tracking in nonresearch clinical settings.

Time frame: selection visit ; T1 (15.5 years old+/-6 months); T2 ( 17.5 years old +/-6 months)

The emotional and sexual relationship

The emotional and sexual relationship assessed by specific questions

Time frame: T0 (13.5 years old +/-6 months); T1 (15.5 years old+/-6 months); T2 ( 17.5 years old +/-6 months)

School drop-out / family breakdown

School drop-out / family breakdown assessed by specific questions

Time frame: T0 (13.5 years old +/-6 months); T1 (15.5 years old+/-6 months); T2 ( 17.5 years old +/-6 months)

Global Assesment Scale (GAS)

assess the adolescent's overall functioning, heteroquestionnaire, score from 1 to 100, on file and after 30-minute interview

Time frame: T2 : 17.5 years old +/-6 months

Potential side-effects

Time frame: T0 (13.5 years old +/-6 months); T1 (15.5 years old+/-6 months); T2 ( 17.5 years old +/-6 months)

Child Behaviour Checklist (CBCL) scale

Emotional disorders and possible comorbidities assessed by the Child Behavior Checklist (CBCL) score, parent self-questionnaire, 15 minutes

Time frame: T0 (13.5 years old +/-6 months); T1 (15.5 years old+/-6 months); T2 ( 17.5 years old +/-6 months)

Youth Self Report (YSR) scale

Emotional disorders and possible comorbidities: assessed by the Youth Self Report (YSR) self-questionnaire, 15 minutes

Time frame: T0 (13.5 years old +/-6 months); T1 (15.5 years old+/-6 months); T2 ( 17.5 years old +/-6 months)

Suicidal risk

Columbia-Suicide Severity Rating Scale (C-SSRS score \>4), in case of suicidal ideation identified through the MINI

Time frame: T0 (13.5 years old +/-6 months); T1 (15.5 years old+/-6 months); T2 ( 17.5 years old +/-6 months)

Evaluation of the Effectiveness of Hormonal Treatment in Adolescents Suffering From Gender Dysphoria

Overview

Conditions

Interventions

Eligibility

Locations (4)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts