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

NCT06351501 | Recruiting Phase 3

• 2 other identifiers: P170923J2019-000300-16
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 4

Brief Summary

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 16. However, in order to reduce the psychosocial consequences of GD, more and more referral teams are carrying out this transition from the age of 14, although no study has been published to show its benefit compared with a transition at the age of 16. 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.

Conditions

Gender Dysphoria

Keywords

Gender Dysphoria; adolescents; hormonal treatment; mental health

Outcome Measures

Primary Outcomes (1)

• 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.

  16 years old +/- 6 months

Secondary Outcomes (16)

• Drug use (DEP-ADO)

  T0 (14 years old +/-6 months); T1 (16 years old+/-6 months); T2 ( 18 years old +/-6 months)

• WISC-V (weschler Test)

  T0 (14 years old +/-6 months); T2 ( 18 years old +/-6 months)

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

  selection visit ; T1 (16 years old +/-6 months) ; T2 (18 years old +/-6 months)

• Beck Depression Inventory (BDI)

  T0 (14 years old +/-6 mois); T1 (16 years old+/-6 monhs); T2 ( 18 years old +/-6 months)

• Body Image Scale (BIS)

  T0 (14 years old +/-6 months); T1 (16 years old+/-6 months); T2 ( 18 years old +/-6 months)

Study Arms (2)

early hormonal treatment

EXPERIMENTAL

early hormonal treatment initiated at 14 years +/- 6 months, in addition to usual care

Drug: hormonal treatment with cross sex hormones (testosterone or oestrogenes) started at 14 years old +/- 6 months

usual treatment

ACTIVE COMPARATOR

Usual care between 14 and 16 years +/- 6 months : child psychiatric consultations, endocrinological consultations and consultations with a psychologist, family interviews, network work with local health partners and national education. Then hormonal treatment initiated at 16 years +/- 6 months, in addition to usual care.

Drug: Cross sex hormones ( œstrogenes or testosterone) started at 16 years old +/- 6 months

Interventions

hormonal treatment with cross sex hormones (testosterone or oestrogenes) started at 14 years old +/- 6 months DRUG

4 years of follow up (FU) with evaluation at T0 (14 years old +/- 6 months), T1 (16 years old +/-6 months) and T2 (18 years old+/- 6 months) with eather ANDROGEL® 16.2 mg/g, gel (testostérone) or ESTREVA® 0.1 %, gel ou 1.3 PROVAMES® 1 mg, cp (oestrogenes)

early hormonal treatment

Cross sex hormones ( œstrogenes or testosterone) started at 16 years old +/- 6 months DRUG

2 years of hormonal treatment from 16 old +/- 6 months to 18 years old +/- 6 months

usual treatment

Eligibility Criteria

• Age: 162 Months - 174 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Adolescents aged 14+/- 6 months,
• Having initiated puberty: tanner score ≥2 for FtM; tanner score ≥2 (clinic and/or testosterone \>0.3 ng/mL) for MtF
• 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.

You may not qualify if:

• Contraindication to hormonal treatment (see paragraph 1.5)
• Hormonal treatment needs to be adjusted (FtM patients treated with anti-coagulants or with thrombophilia).
• Patients with risk of aggravation of certain diseases under oestrogen treatment (MtF 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
• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (4)

Service de psychiatrie de l'enfant et de l'adolescent, GH Pitié-Salpêtrière

Paris, Paris, 75013, France

RECRUITING

Service d'Endocrinologie et Diabétologie Pédiatrique, CHU Robert Debré

Paris, Paris, 75019, France

RECRUITING

Service de Psychiatrie de l'enfant et de l'adolescent, CHU Robert Debré

Paris, Paris, 75019, France

RECRUITING

Service Endocrinologie et Diabète de l'enfant, CHU Le Kremlin Bicêtre

Le Kremlin-Bicêtre, Île-de-France Region, 94270, France

NOT YET RECRUITING

MeSH Terms

Conditions

Gender Dysphoria; Psychological Well-Being

Interventions

Testosterone

Condition Hierarchy (Ancestors)

Sexual Dysfunctions, Psychological; Mental Disorders; Personal Satisfaction; Behavior

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• David COHEN, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  STUDY DIRECTOR

Central Study Contacts

David COHEN, MD,PhD

CONTACT

01 42 16 23 51; david.cohen@aphp.fr

Anne BISSERY

CONTACT

(0)142162432; anne.bissery@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The assessment of the primary criteria will be carried out by a psychologist who will have no knowledge of the teenager's allocation group and will not have been involved in his or her care. At T1, the assessment will be based on key elements of the patient's file provided to him or her without any element that could indicate his or her allocation group or original gender, and a telephone interview with the teenager and his or her parents in which they will have been told in advance not to reveal the allocation group or gender. The psychologist who assesses a 16-year-old will be different from the one who assesses a 14-year-old. Psychological assessments other than the primary criterion, and the assessment by the pediatric endocrinologist, will take place at the site of the patient's usual care. Adolescents will be monitored as part of their usual care.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 2, 2024
• First Posted: April 8, 2024
• Study Start: June 25, 2024
• Primary Completion (Estimated): June 24, 2029
• Study Completion (Estimated): June 24, 2031
• Last Updated: March 13, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (4)