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Gender DysphoriaPhase 4NCT02715232

Effects of Sex Steroids on the Serotonin System

A Phase 4 study testing Testosterone, Lynestrenol and Cyproterone Acetate in people with Gender Dysphoria, run by Medical University of Vienna at 1 site in Austria.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The aim of this study is to prove the modulatory influence of sex hormones on serotonergic neurotransmission by determining the enzymatic processes involved in serotonin synthesis and degradation using positron emission tomography (PET) in humans in vivo with the radiotracers [11C]AMT and [11C]harmine. Read more about this study

Who is it for?
Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for
Gender Dysphoria
What is being tested?
Testosterone, Lynestrenol and Cyproterone Acetate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
92 participants
Where
1 siteAustria
Study dates
6 Feb 2017to Dec 2020
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • DSM-5 diagnosis of Gender Dysphoria (DSM-5: 302.85; ICD-10: F64.1) (for transsexuals only)
  • Somatic health based on history, physical examination, ECG, laboratory screening, SCID
  • willingness and competence to sign the informed consent form

Who cannot join

  • concomitant major medical or neurological illness
  • internal or neurologic medical histories as well as pregnancy (positive urine pregnancy test) or breastfeeding
  • other DSM-5 Axis-I comorbidities, determined by a structured clinical interview (SCID), especially body dysphoric disorder (DSM-5: 300.7; ICD-10: F45.22), schizophrenia spectrum and other psychotic disorders
  • steroid hormone treatment within 6 months prior to inclusion
  • treatment with psychotropic agents such as SSRIs
  • any implant or stainless steel graft
Show all 10Show fewer
  • abnormal values in routine laboratory screening or general physical examination
  • current substance abuse or current or past substance related disorder
  • for participants who participated in an earlier neuroimaging study using ionizing radiation, the total radiation exposure dose of 20 mSv over the last 10 years must not be exceeded, as specified in the legislation on radiation protection (Allg. Strahlenschutzverordnung 2010; www.ris.bka.gv.at)
  • failure to comply with the study protocol or to follow the instructions of the investigating team

Trial locations and contacts

1 site in 1 country.

Austria1 site, 1 recruiting
  • Department of Psychiatry and Psychotherapy, Medical University of Vienna

    Vienna, 1090

    Rupert Lanzenberger, A/Prof., +43 40400 ext. 3825, rupert.lanzenberger@meduniwien.ac.at

    Rupert Lanzenberger, A/Prof. MD

    Recruiting

Other trials in Austria

About this study

Official title: Effects of Sex Steroid Hormones on Serotonin Synthesis and Degradation Measured With PET

The aim of this study is to prove the modulatory influence of sex hormones on serotonergic neurotransmission by determining the enzymatic processes involved in serotonin synthesis and degradation using positron emission tomography (PET) in humans in vivo with the radiotracers [11C]AMT and [11C]harmine.

Read the detailed description

Background:

Sex hormones such as estradiol and testosterone modulate human brain structure and function and are tightly connected to neuropsychiatric disorders such as depression and anxiety disorders. Using molecular imaging in humans in vivo, the investigators showed strong influences of sex hormones on serotonergic neurotransmission via modulation of serotonergic receptors and transporters. Although, animal studies also indicate strong modulatory influences on serotonin synthesis and degradation, human data on this potential effect are absent.

Objectives of the study:

The aim of this study is to prove the modulatory influence of sex hormones on serotonergic neurotransmission by determining the enzymatic processes involved in serotonin synthesis and degradation using positron emission tomography (PET) in humans in vivo with the radiotracers [11C]AMT and [11C]harmine.

Study design:

Single-blind, longitudinal study. Transsexuals will undergo four PET and two magnetic resonance imaging (MRI) measurements: 1. One [11C]AMT PET, one [11C]harmine PET and one MRI measurement before start of treatment, 2. One [11C]AMT PET, one [11C]harmine PET and one MRI measurement after 4 months of treatment. The investigators propose an overall study duration of 36 months.

Materials and Methods:

PET measurements will be performed on a GE Advance PET scanner. To examine the interdependence between serotonin activity and brain structure and function, four MRI sequences will be performed in order to assess gray matter volume and cortical thickness, gray and white matter microstructure, as well as resting state functional connectivity and cerebral blood flow. MRI measurements will be done on a 3 Tesla scanner with high spatial and temporal resolution.

Study population:

20 healthy female-to-male (FtM), 20 healthy male-to-female (MtF) transsexuals (aged 18-50) who are free of hormone-medication at baseline; 40 healthy controls, matched for sex, age and education level.

Pilot Study:

A pilot study without pharmacologic intervention consisting of one optional [11C]AMT PET and two [11C]harmine PET will be performed in 12 healthy controls in order to optimise PET measurement procedures.

Relevance and implications of the study:

This will be the first imaging study to investigate the effects of high-dose, long-term opposite-sex steroid hormones on serotonin synthesis and degradation in the living human brain using PET. The study will lead to the establishment of a comprehensive theory of serotonergic modulation by sex steroids and will increase knowledge on the serotonergic role in shaping brain morphology, microstructure and structural/functional connectivity. Results will provide essential data for a better understanding of neural sex differences associated with differences in hormonal states in humans and will elucidate neurobiological correlates of the known gender difference in the prevalence of neuropsychiatric disorders, thus contributing to the development of personalized treatment, the reduction of personal suffering and the reduction of costs and occupational disability.

Being tested
Testosterone, Lynestrenol, Cyproterone Acetate, Estradiol, Triptorelin acetate
Medical subject headings
Gender Dysphoria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TestosteroneDrug

    100mg testosterone undecanoat every 8-12 weeks, or alternatively 50mg testosterone transdermally, or 50mg testosterone creme

  • LynestrenolDrug

    2-3 tablets/day, if menstruation still occurs

  • Cyproterone AcetateDrug

    25mg daily

  • EstradiolDrug

    75 microgram transdermal therapeutic system twice a week, or p.o. estradiol 2x2mg/day, or estradiol gel 1,5-3mg

  • Triptorelin acetateDrug

    4,12mg every 4-6 weeks (powder for suspension for injection s.c. or i.m.

Study groups in NCT02715232
Study groupRoleWhat they receive
Female-to-MalesExperimentalFemale-to-Male Transsexuals receiving Testosterone treatment
Receives: Drug: Testosterone; Drug: Lynestrenol; Drug: Triptorelin acetate
Male-to-FemalesExperimentalMale-to-Female Transsexuals receiving Estradiol and Anti-androgen treatment
Receives: Drug: Cyproterone Acetate; Drug: Estradiol; Drug: Triptorelin acetate
Female ControlsNo interventionFemale Controls receiving no intervention
Male ControlsNo interventionMale controls receiving no intervention

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. blood-to-brain clearance/trapping (K*) of [11C]AMT

    [11C]AMT trapping as an estimation of brain serotonin synthesis in vivo in humans

    Measured: <5 months

  2. distribution volume (DV) of [11C]harmine

    distribution volume of specifically bound radioligand [11C]harmine in brain regions

    Measured: <5 months

Secondary outcomes (5)
  1. white and gray matter microstructure

    microstructure measured using diffusion weighted imaging

    Measured: <5 months

  2. gray matter volume/density and cortical thickness

    structural MRI measurements

    Measured: <5 months

  3. cerebral blood flow (CBF)

    cerebral blood flow measured using arterial spin labeling MRI

    Measured: <5 months

  4. Scores on the Klein Sexual Orientation Grid (KSOG)

    the KSOG measures sexual orientation

    Measured: <5 months

  5. Scores on the Utrecht Gender Dysphoria Scale

    Score for gender dysphoria

    Measured: <5 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Mar 2016 (estimated)
  2. Study start6 Feb 2017
  3. Primary completionDec 2020 (estimated)
  4. Study completionDec 2020 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Basic science
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
92 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02715232
Sponsor's protocol ID
1.1-20150511
Status last verified
Oct 2018
First submitted
16 Mar 2016
Last updated
15 Oct 2018
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes

Publications

  • Kranz GS, Wadsak W, Kaufmann U, Savli M, Baldinger P, Gryglewski G, Haeusler D, Spies M, Mitterhauser M, Kasper S, Lanzenberger R. High-Dose Testosterone Treatment Increases Serotonin Transporter Binding in Transgender People. Biol Psychiatry. 2015 Oct 15;78(8):525-33. doi: 10.1016/j.biopsych.2014.09.010. Epub 2014 Sep 23.

    PubMed 25497691
  • Kranz GS, Hahn A, Kaufmann U, Kublbock M, Hummer A, Ganger S, Seiger R, Winkler D, Swaab DF, Windischberger C, Kasper S, Lanzenberger R. White matter microstructure in transsexuals and controls investigated by diffusion tensor imaging. J Neurosci. 2014 Nov 12;34(46):15466-75. doi: 10.1523/JNEUROSCI.2488-14.2014.

    PubMed 25392513
  • Hahn A, Kranz GS, Kublbock M, Kaufmann U, Ganger S, Hummer A, Seiger R, Spies M, Winkler D, Kasper S, Windischberger C, Swaab DF, Lanzenberger R. Structural Connectivity Networks of Transgender People. Cereb Cortex. 2015 Oct;25(10):3527-34. doi: 10.1093/cercor/bhu194. Epub 2014 Sep 12.

    PubMed 25217469
  • Hahn A, Kranz GS, Sladky R, Kaufmann U, Ganger S, Hummer A, Seiger R, Spies M, Vanicek T, Winkler D, Kasper S, Windischberger C, Swaab DF, Lanzenberger R. Testosterone affects language areas of the adult human brain. Hum Brain Mapp. 2016 May;37(5):1738-48. doi: 10.1002/hbm.23133. Epub 2016 Feb 15.

    PubMed 26876303
  • Smith LJ, Henderson JA, Abell CW, Bethea CL. Effects of ovarian steroids and raloxifene on proteins that synthesize, transport, and degrade serotonin in the raphe region of macaques. Neuropsychopharmacology. 2004 Nov;29(11):2035-45. doi: 10.1038/sj.npp.1300510.

    PubMed 15199371
  • Aggarwal M, Puri V, Puri S. Effects of estrogen on the serotonergic system and calcitonin gene-related peptide in trigeminal ganglia of rats. Ann Neurosci. 2012 Oct;19(4):151-7. doi: 10.5214/ans.0972.7531.190403.

    PubMed 25205989
  • Purves-Tyson TD, Handelsman DJ, Double KL, Owens SJ, Bustamante S, Weickert CS. Testosterone regulation of sex steroid-related mRNAs and dopamine-related mRNAs in adolescent male rat substantia nigra. BMC Neurosci. 2012 Aug 6;13:95. doi: 10.1186/1471-2202-13-95.

    PubMed 22867132
  • Klobl M, Reed MB, Handschuh P, Kaufmann U, Konadu ME, Ritter V, Spurny-Dworak B, Kranz GS, Lanzenberger R, Spies M. Gender Dysphoria and Sexual Euphoria: A Bayesian Perspective on the Influence of Gender-Affirming Hormone Therapy on Sexual Arousal. Arch Sex Behav. 2024 May;53(5):1859-1871. doi: 10.1007/s10508-023-02778-1. Epub 2024 Jan 12.

    PubMed 38216784

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Testosterone, Lynestrenol and Cyproterone Acetate in people with Gender Dysphoria, run by Medical University of Vienna at 1 site in Austria.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 15 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Rupert Lanzenberger, MD (+43 40400 ext. 35760, rupert.lanzenberger@meduniwien.ac.at), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

blood-to-brain clearance/trapping (K*) of [11C]AMT (time frame: <5 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02715232, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2018.

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