Effects of Sex Steroids on the Serotonin System

October 12, 2018 updated by: Rupert Lanzenberger, Medical University of Vienna

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

92

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Vienna, Austria, 1090
        • Recruiting
        • Department of Psychiatry and Psychotherapy, Medical University of Vienna
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Female-to-Males
Female-to-Male Transsexuals receiving Testosterone treatment
Drug: Testosterone
100mg testosterone undecanoat every 8-12 weeks, or alternatively 50mg testosterone transdermally, or 50mg testosterone creme
Drug: Lynestrenol
2-3 tablets/day, if menstruation still occurs
Drug: Triptorelin acetate
4,12mg every 4-6 weeks (powder for suspension for injection s.c. or i.m.
Experimental: Male-to-Females
Male-to-Female Transsexuals receiving Estradiol and Anti-androgen treatment
Drug: Triptorelin acetate
4,12mg every 4-6 weeks (powder for suspension for injection s.c. or i.m.
Drug: Cyproterone Acetate
25mg daily
Drug: Estradiol
75 microgram transdermal therapeutic system twice a week, or p.o. estradiol 2x2mg/day, or estradiol gel 1,5-3mg
No Intervention: Female Controls
Female Controls receiving no intervention
No Intervention: Male Controls
Male controls receiving no intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
blood-to-brain clearance/trapping (K*) of [11C]AMT
Time Frame: <5 months
[11C]AMT trapping as an estimation of brain serotonin synthesis in vivo in humans
<5 months
distribution volume (DV) of [11C]harmine
Time Frame: <5 months
distribution volume of specifically bound radioligand [11C]harmine in brain regions
<5 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
white and gray matter microstructure
Time Frame: <5 months
microstructure measured using diffusion weighted imaging
<5 months
gray matter volume/density and cortical thickness
Time Frame: <5 months
structural MRI measurements
<5 months
cerebral blood flow (CBF)
Time Frame: <5 months
cerebral blood flow measured using arterial spin labeling MRI
<5 months
Scores on the Klein Sexual Orientation Grid (KSOG)
Time Frame: <5 months
the KSOG measures sexual orientation
<5 months
Scores on the Utrecht Gender Dysphoria Scale
Time Frame: <5 months
Score for gender dysphoria
<5 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical University of Vienna

Investigators

  • Principal Investigator: Rupert Lanzenberger, MD, Department of Psychiatry and Psychotherapy, Medical University of Vienna

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 6, 2017

Primary Completion (Anticipated)

December 1, 2020

Study Completion (Anticipated)

December 1, 2020

Study Registration Dates

First Submitted

March 16, 2016

First Submitted That Met QC Criteria

March 21, 2016

First Posted (Estimate)

March 22, 2016

Study Record Updates

Last Update Posted (Actual)

October 15, 2018

Last Update Submitted That Met QC Criteria

October 12, 2018

Last Verified

October 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1.1-20150511

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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