Clinical Trial: Effects of Sex Steroids on the Serotonin System

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

Brief 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.

Detailed Summary:

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 res
Sponsor: Medical University of Vienna

Current Primary Outcome:

  • 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
  • distribution volume (DV) of [11C]harmine [ Time Frame: <5 months ]
    distribution volume of specifically bound radioligand [11C]harmine in brain regions


Original Primary Outcome: Same as current

Current Secondary Outcome:

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


Original Secondary Outcome:

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


Information By: Medical University of Vienna

Dates:
Date Received: March 16, 2016
Date Started: February 6, 2017
Date Completion: December 2020
Last Updated: April 12, 2017
Last Verified: April 2017