Condition category
Mental and Behavioural Disorders
Date applied
02/05/2007
Date assigned
02/05/2007
Last edited
21/09/2007
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr F.M. Wouters

ORCID ID

Contact details

VU Medical Centre
Department of Pediatrics
1Y125
Boelelaan 1117
Amsterdam
1081 HV
Netherlands
+31 (0)20 444 1035
f.wouters@vumc.nl

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Acronym

Clinical study on transsexual adolescents

Study hypothesis

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

Approval received from the local medical ethics committee (Medisch Ethische Toetsingscommissie VU medisch centrum) on the 15th of February 2007 (ref: 2006/292).

Study design

Observational, parallel group, multicentre, case-control study

Primary study design

Observational

Secondary study design

Case-control study

Trial setting

Not specified

Trial type

Not Specified

Patient information sheet

Condition

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 names

Triptorelin

Primary outcome measures

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

Secondary outcome measures

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

Overall trial start date

01/02/2007

Overall trial end date

31/12/2009

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Child

Gender

Both

Target number of participants

264

Participant 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

Recruitment start date

01/02/2007

Recruitment end date

31/12/2009

Locations

Countries of recruitment

Netherlands

Trial participating centre

VU Medical Centre
Amsterdam
1081 HV
Netherlands

Sponsor information

Organisation

Vrije University Medical Centre (VUMC) (The Netherlands)

Sponsor details

Department of Paediatric Endocrinology
P.O. Box 7057
Amsterdam
1007 MB
Netherlands

Sponsor type

Hospital/treatment centre

Website

http://www.vumc.nl/english/

Funders

Funder type

Industry

Funder name

Ferring Pharmaceuticals A/S (Denmark)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Protocol on:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17074986

Publication citations

Additional files

Editorial Notes