Brain development, brain functioning, growth and metabolic aspects in the clinical management of transsexual adolescents

ISRCTN	ISRCTN81574253
DOI	https://doi.org/10.1186/ISRCTN81574253
Protocol serial number	N/A
Sponsor	Vrije University Medical Centre (VUMC) (The Netherlands)
Funder	Ferring Pharmaceuticals

Submission date: 02/05/2007
Registration date: 02/05/2007
Last edited: 06/08/2021

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Mental and Behavioural Disorders

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr F.M. Wouters
Scientific

VU Medical Centre
Department of Pediatrics, 1Y125
Boelelaan 1117
Amsterdam
1081 HV
Netherlands

Phone	+31 (0)20 444 1035
Email	f.wouters@vumc.nl

Study information

Primary study design	Observational
Study design	Observational, parallel group, multicentre, case-control study
Secondary study design	Case-control study
Scientific title	Brain development, brain functioning, growth and metabolic aspects in the clinical management of transsexual adolescents
Study acronym	Clinical study on transsexual adolescents
Study objectives	The hypothesis of this study is that the pubertal delay in transsexual adolescents, induced by treatment with Gonadotropin-Releasing Hormone (GnRH) analogues, will cause a difference in the development of brain structures and brain function between transsexuals and age matched control subjects without transsexuality. If cross-sex hormones are added from the age of sixteen, a catch up of brain development is expected. It is of great interest to investigate if this brain development will occur in the direction of the biologic or desired sex. Gender dysphoria is associated with atypical levels of sex hormones during pregnancy. The hypothesis of this study is that already at a young age, development of brain structures and brain function in gender dysphoric children will occur in the direction of the desired instead of the biologic sex.
Ethics approval(s)	Approval received from the local medical ethics committee (Medisch Ethische Toetsingscommissie VU medisch centrum) on the 15th of February 2007 (ref: 2006/292).
Health condition(s) or problem(s) studied	Transsexuality
Intervention	Patients: Measurements will be performed at a prepubertal stage, before start of GnRH analogue Triptoreline/Decapeptyl-CR (current puberty delaying medication for transsexual adolescents in the VUmc from the age of 12 and if puberty has already started, i.e., Tanner stage B2 in girls, G1-2 in boys), before start of cross-sex hormones (17-beta oestradiol in male-to-female transsexuals and sustanon in female-to-male transsexuals), one year after start of cross-sex hormones and one to two years after gender reassignment surgery. Age matched control subjects (friends of the transsexual patients): Measurements will be performed if the transsexual friend starts with puberty delaying treatment, if the transsexual friend starts with cross-sex hormones and one to two years after surgery of the transsexual friend. Interventions: 1. Structural Magnetic Resonance Imaging (MRI); method used: a. voxel-based morphometry b. Region Of Interest (ROI) analysis 2. Functional MRI (Blood Oxygenation Level-Dependent [BOLD]) during which three cognition tasks will be performed (mental rotation, verbal fluency and emotional faces) 3. Physical examination with anthropometric measurements and gathering of information about pubertal stage according to Tanner 4. Digital photographs and physical appearance list 5. Salivary testosterone measurements 6. Family pedigree research: homosexuality/transsexuality in family The duration of the intervention will be approximately three hours for any visit, which means at maximum five visits (if patients will be followed longitudinally) for the patients and three visits (if control subjects will be followed longitudinally) for the control subjects.
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Triptorelin
Primary outcome measure(s)	1. Cognition: performance and reaction time on three cognition tasks (verbal fluency task, mental rotation task and emotional faces task), reaction times and performance will be measured 2. Functional MRI: data during the verbal fluency task, mental rotation task and emotional faces task 3. Structural MRI: data on total brain volume, grey and white matter (amount and percentage), Cerebrospinal Fluid (CSF), volume frontal and temporal lobe, gyrification, brain asymmetry. ROI analysis of basal ganglia, amygdala, hippocampus, corpus callosum, hypothalamus The timepoints at which the primary and secondary outcomes are measured for the patients are: 1. Prepubertal stage 2. Before start of GnRH analogue Triptoreline/Decapeptyl-CR (current puberty delaying medication for transsexual adolescents in the VUmc from the age of 12 and if puberty has already started, i.e., Tanner stage B2 in girls, G1-2 in boys) 3. Before start of cross-sex hormones (17-beta oestradiol in male-to-female transsexuals and sustanon in female-to-male transsexuals) 4. One year after start of cross-sex hormones 5. One to two years after gender reassignment surgery The timepoints for the control subjects are related to the time points of the patients, for they are age-matched friends of the patients. These timepoints are: 1. The moment that the transsexual friend starts with puberty delaying treatment 2. The moment that the transsexual friend starts with cross-sex hormones 3. One to two years after surgery of the transsexual friend
Key secondary outcome measure(s)	1. Score from -10 to 10 on handedness questionnaire 2. Performance score on adapted Wechsler Intelligence Scale for Children-III (WISC-III) questionnaire (four items: two performance, two verbal) 3. Information about psychological functioning (parent questionnaire) 4. Anthropometric data, information about pubertal stage according to Tanner 5. Information about homosexuality/transsexuality in family members 6. Digital photographs and physical appearance list (14 items) The timepoints at which the primary and secondary outcomes are measured for the patients are: 1. Prepubertal stage 2. Before start of GnRH analogue Triptoreline/Decapeptyl-CR (current puberty delaying medication for transsexual adolescents in the VUmc from the age of 12 and if puberty has already started, i.e., Tanner stage B2 in girls, G1-2 in boys) 3. Before start of cross-sex hormones (17-beta oestradiol in male-to-female transsexuals and sustanon in female-to-male transsexuals) 4. One year after start of cross-sex hormones 5. One to two years after gender reassignment surgery The timepoints for the control subjects are related to the time points of the patients, for they are age-matched friends of the patients. These timepoints are: 1. The moment that the transsexual friend starts with puberty delaying treatment 2. The moment that the transsexual friend starts with cross-sex hormones 3. One to two years after surgery of the transsexual friend
Completion date	31/12/2009

Eligibility

Participant type(s)	Mixed
Age group	Child
Sex	All
Target sample size at registration	264
Key inclusion criteria	Inclusion criteria - pubertal patients: 1. Girls and boys with transsexualism who are eligible for sex reassignment according to psychologist and psychiatrist (if they are older than 12 years, psychologically stable and live in a stable social environment) 2. Girls have to be in stage B2 and boys in G2-G3 with measurable oestradiol and testosterone levels respectively Inclusion criteria - pre-pubertal patients: 1. Girls and boys with high probability of transsexualism according to psychologist or psychiatrist and the age of 9 to 12 years 2. Girls have to be in an earlier stage than B2 and boys in an earlier stage than G2-G3 Inclusion criteria - healthy subjects: 1. Girls and boys who are similar aged friends of the transsexual patients
Key exclusion criteria	Exclusion criteria - patients: 1. Intersex conditions Exclusion criteria - healthy subjects: 1. Puberty delaying treatment or hormonal therapy; oral anticonception users are not excluded
Date of first enrolment	01/02/2007
Date of final enrolment	31/12/2009

Locations

Countries of recruitment

Netherlands

Study participating centre

VU Medical Centre

Amsterdam
1081 HV
Netherlands

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	01/07/2017	06/08/2021	Yes	No
Results article	01/12/2020	06/08/2021	Yes	No
Results article	22/02/2013	06/08/2021	Yes	No
Results article	30/01/2015	06/08/2021	Yes	No
Results article	01/07/2016	06/08/2021	Yes	No
Abstract results			No	No

Editorial Notes

06/08/2021: Publication references added.