Gender DysphoriaNCT03651427
Cross-sex Hormone Therapy and Neuronal Plasticity
A study testing Estradiol in people with Gender Dysphoria, run by Hospital de Clinicas de Porto Alegre at 1 site in Brazil.
Trial summary
Transgender women (male-to-female) were invited to participate in this study to test the impact of Cross-Sex Hormone Therapy (CSHT) in the brain. Neuroimaging and cognitive assessment were performed in different time-points to compare the impact of CSHT in the brain. Read more about this study
- Who is it for?
- Ages 18 to 60 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Gender Dysphoria
- What is being tested?
- Estradiol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteBrazil
- Study dates
- 13 Feb 2017to 30 Mar 2019
- Phase
- Interventional
- 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 60 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Transgender women
- Age 18 to 60 years old.
Who cannot join
- Use of psychostimulant drugs
- Use of Antidepressive, Mood Stabiliser, Anti-psychotic, Benzodiazepines, anti-convulsivants, Anorexigenic
- Endocrinological disease (other than diabetes)
- Arterial Hypertensive Disease of Diabetes Mellitus out of control target
- Neurological disease, including stroke or recent cranial trauma with loss or consciousness
- HIV with low CD4 or high viral charge or symptomatic AIDS
- Neoplasia
Trial locations and contacts
1 site in 1 country.
Brazil1 site, 1 recruiting
- Recruiting
Hospital de Clínicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90035-903
Maiko Schneider, MD, 5551997722606, maikoschneider@hcpa.edu.br
About this study
Official title: Neuroactive Sex Steroids And Their Influence In Glutamatergic Neurotransmission - Effects in Memory and Cognition in Transgender People
Transgender women (male-to-female) were invited to participate in this study to test the impact of Cross-Sex Hormone Therapy (CSHT) in the brain.
Neuroimaging and cognitive assessment were performed in different time-points to compare the impact of CSHT in the brain.
Read the detailed description
Sex hormones are known to exert several effect on the brain white matter, cerebral cortex, functional connectivity and neurotransmission. Furthermore, in transgender people, CSHT is know to induce anatomical and functional changes in the brain. However, only a few studies have already been conducted to investigate the effects of sex hormones on the brain accounting for the interference of endogenous gonadal hormones. Also, there is a lack of knowledge about the importance of CSHT after Gender Affirming Surgery (GAS) regarding induced hypogonadism that follows this surgical procedure. Therefore, neuroimaging studies designed to isolate the effect of endogenous gonadal hormones in people with GD urge to be developed.
To fulfil this purpose, transgender women that have already performed GAS and/or were under Gonadotrophin Release Hormone analogues treatment (in order to induce hypogonadism similar to GAS) were invited to interrupt CSHT for at least 30 days to promote sex hormones washout. At the end of the washout, participants performed magnetic resonance imaging, laboratorial analyses for sex hormones and neuro-cognitive assessment. After this first time-point, participants received a new prescription for CSHT containing estradiol (without progesterone) to be used continuously for 60 days, when the same assessments from the end of washout were repeated 60 days after CSHT to compare brain and cognitive longitudinal changes.
At all the time-points, variations in depression scores and anxiety levels were assessed with specific scales.
- Conditions
- Gender Dysphoria
- Being tested
- Estradiol
- Keywords
- Estradiol;, Brain, glutamate, spectroscopy, hypogonadism
- Medical subject headings
- Gender Dysphoria, Hypogonadism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EstradiolDrug
Also called Drug washout
Induced hypogonadism and re-institution of CSHT
| Study group | Role | What they receive |
|---|---|---|
| Transgender Women | Experimental | Transgender women who already completed GAS or that agreed to start gonadotropin release hormone analogue to suppress endogenous sex hormones.
If the participants were using CSHT in the moment of the study assignment, they were asked to stop hormones for 30 days to evaluate the impact of hypogonadism in the brain.
After this first assessment, they received prescriptions for Estradiol (equine conjugated oestrogen, or estradiol valerate, or topic 17-beta estradiol formulations) for 60 days, and the impact of CSHT was evaluated again to compare to washout condition. Receives: Drug: Estradiol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glutamate concentration in the left hippocampus
Proton Spectroscopy - magnetic resonance imaging;
Glutamate concentration in the left hippocampus will be primarily correlated to working memory scores.
Measured: 90 days
Secondary outcomes (9)
Cortical Thickness
Anatomical magnetic resonance imaging
Measured: 90 days
Diffusion track imaging
Micro-Structural magnetic resonance imaging
Measured: 90 days
functional connectivity
functional magnetic resonance imaging
Measured: 90 days
Glutamate concentration in the anterior cingulate cortex and left dorsolateral prefrontal cortex
Proton spectroscopy - magnetic resonance imaging; Glutamate concentration in the left dorsolateral prefrontal cortex will be correlated to over all measures of cognition and executive functioning.
Measured: 90 days
Cognition
Instrument: Wechsler Adult Intelligence Scale (WAIS) version 3. Subscale: Full Scale Intelligence coefficient. Mean: 100 Standard deviation (SD):15 for Brazilian population. Range of classification: 69 and below - Extremely Low 70-79 - Borderline 80-89 - Low Average 90-109 - Average 110-119 - High Average 120-129 - Superior 130 and above - very superior
Measured: 90 days
Operational memory
Subscale from Wechsler Adult Intelligence Scale (WAIS) version 3. Mean: 100 Standard deviation (SD):15 for Brazilian population. 69 and below - Extremely Low 70-79 - Borderline 80-89 - Low Average 90-109 - Average 110-119 - High Average 120-129 - Superior 130 and above - very superior
Measured: 90 days
Verbal memory
Rey Auditory-Verbal Learning Test (RAVLT). Mean and range for Brazilian population:
- A1 (Verbal Memory - Immediate recall). Range (in Z-scores): Z <-1.5 are classified as deficit; Z >-1.5 are expected
- A5 (Verbal Memory - immediate recall). Range (in Z-scores): Z <-1.5 are classified as deficit; Z >-1.5 are expected
- A7 (Verbal Memory - late recall). Range in (Z-scores): Z <-1.5 are classified as deficit; Z >-1.5 are expected
- Learning Over Trial (LOT) (Learning capacity). Range (in Z-scores): Z <-1.5 are classified as deficit; Z >-1.5 are expected (please, note the reference for Brazilian population in the section "references" where the mean and standard deviation according to Brazilian population are described for each of the subtest; Salgado et al. (2011).
Measured: 90 days
Language (Verbal Fluency)
Verbal Fluency Tests: (FAS) and Animals.
Mean and standard deviation (SD) according to age range and years of education:
Age range for the test: 16-59 years
Score classification according to years of education:
- From 0 to 8 years of education: Mean: 38.8 SD: 12.0
- From 9 to 12 years of education: Mean: 40.5 SD: 10.7
- From 12 to 21 years of education:
Mean: 44.7 SD:11.2
Range in Z-scores: Z <-1.5 are classified as deficit; Z >-1.5 are expected
Measured: 90 days
Executive function
Stroop Test -Victoria Version.
Mean and standard deviation (SD) according to the age range and years of education:
For 19-39 years old + 5-8 years of education:
Mean: 33.3 SD:11.35
For 19-39 years old + 9 or more years of education:
Mean: 41.73 SD: 9.85
For 40-59 years old + 5-8 years of education:
Mean: 28 SD: 7.76
For 40-59 years old + 9 or more years of education:
Mean: 37.17 SD: 9.98
Range in Z-scores:
Z <-1.5 are classified as deficit; Z >-1.5 are expected
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2018
- Study start13 Feb 2017
- Primary completion30 Mar 2019 (estimated)
- Study completion30 Mar 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Gender DysphoriaStudies of the same condition, open and under way.
- More trials run by Hospital de Clinicas de Porto AlegreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Sel-controlled case series
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital de Clinicas de Porto Alegre
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Maria Lobato, Dr, Principal investigator, Hospital de Clinicas de Porto Alegre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03651427
- Sponsor's protocol ID
- 150199a
- Status last verified
- Aug 2018
- First submitted
- 24 Aug 2018
- Last updated
- 29 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Salgado JV, Malloy-Diniz LF, Abrantes SS, Moreira L, Schlottfeldt CG, Guimaraes W, Freitas DM, Oliveira J, Fuentes D. Applicability of the Rey auditory-verbal learning test to an adult sample in Brazil. Braz J Psychiatry. 2011 Sep;33(3):234-7. doi: 10.1590/s1516-44462011005000007.
PubMed 21971775
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuroactive Sex Steroids And Their Influence In Glutamatergic Neurotransmission - Effects in Memory and Cognition in Transgender People
- ClinicalTrials.gov ID
- NCT03651427
- Acronym / sponsor ID
- 150199a
- Conditions
- Gender Dysphoria
- Keywords
- Estradiol;, Brain, glutamate, spectroscopy, hypogonadism
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Hospital de Clinicas de Porto AlegreUniversity, hospital or other
- Study start
- 13 Feb 2017 (actual)
- Primary completion
- 30 Mar 2019 (estimated)
- Study completion
- 30 Mar 2019 (estimated)
- First posted
- 29 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Transgender women (male-to-female) were invited to participate in this study to test the impact of Cross-Sex Hormone Therapy (CSHT) in the brain.
Neuroimaging and cognitive assessment were performed in different time-points to compare the impact of CSHT in the brain.
Detailed description
Sex hormones are known to exert several effect on the brain white matter, cerebral cortex, functional connectivity and neurotransmission. Furthermore, in transgender people, CSHT is know to induce anatomical and functional changes in the brain. However, only a few studies have already been conducted to investigate the effects of sex hormones on the brain accounting for the interference of endogenous gonadal hormones. Also, there is a lack of knowledge about the importance of CSHT after Gender Affirming Surgery (GAS) regarding induced hypogonadism that follows this surgical procedure. Therefore, neuroimaging studies designed to isolate the effect of endogenous gonadal hormones in people with GD urge to be developed.
To fulfil this purpose, transgender women that have already performed GAS and/or were under Gonadotrophin Release Hormone analogues treatment (in order to induce hypogonadism similar to GAS) were invited to interrupt CSHT for at least 30 days to promote sex hormones washout. At the end of the washout, participants performed magnetic resonance imaging, laboratorial analyses for sex hormones and neuro-cognitive assessment. After this first time-point, participants received a new prescription for CSHT containing estradiol (without progesterone) to be used continuously for 60 days, when the same assessments from the end of washout were repeated 60 days after CSHT to compare brain and cognitive longitudinal changes.
At all the time-points, variations in depression scores and anxiety levels were assessed with specific scales.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Sel-controlled case series
| Arm | Type | Receives |
|---|---|---|
| Transgender Women | Experimental | Drug: EstradiolTransgender women who already completed GAS or that agreed to start gonadotropin release hormone analogue to suppress endogenous sex hormones. If the participants were using CSHT in the moment of the study assignment, they were asked to stop hormones for 30 days to evaluate the impact of hypogonadism in the brain. After this first assessment, they received prescriptions for Estradiol (equine conjugated oestrogen, or estradiol valerate, or topic 17-beta estradiol formulations) for 60 days, and the impact of CSHT was evaluated again to compare to washout condition. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Transgender women
- Age 18 to 60 years old.
Key exclusion criteria (7 listed)
- Use of psychostimulant drugs
- Use of Antidepressive, Mood Stabiliser, Anti-psychotic, Benzodiazepines, anti-convulsivants, Anorexigenic
- Endocrinological disease (other than diabetes)
- Arterial Hypertensive Disease of Diabetes Mellitus out of control target
- Neurological disease, including stroke or recent cranial trauma with loss or consciousness
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EstradiolAlso: Drug washoutInduced hypogonadism and re-institution of CSHT | Drug | Transgender Women |
Primary outcome
Glutamate concentration in the left hippocampus
Time frame: 90 days
Proton Spectroscopy - magnetic resonance imaging; Glutamate concentration in the left hippocampus will be primarily correlated to working memory scores.
9 secondary outcomes
Cortical Thickness
Time frame: 90 days
Diffusion track imaging
Time frame: 90 days
functional connectivity
Time frame: 90 days
Glutamate concentration in the anterior cingulate cortex and left dorsolateral prefrontal cortex
Time frame: 90 days
Cognition
Time frame: 90 days
Operational memory
Time frame: 90 days
Verbal memory
Time frame: 90 days
Language (Verbal Fluency)
Time frame: 90 days
Executive function
Time frame: 90 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2018.
- Results publication: PubMed 21971775Salgado JV, Malloy-Diniz LF, Abrantes SS, Moreira L, Schlottfeldt CG, Guimaraes W, Freitas DM, Oliveira J, Fuentes D. Applicability of the Rey auditory-verbal learning test to an adult sample in Brazil. Braz J Psychiatry. 2011 Sep;33(3):234-7. doi: 10.1590/s1516-44462011005000007.
- This references is related to the "verbal memory" evaluation, described in the outcomes.Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maria Lobato, Dr principal investigator
Hospital de Clinicas de Porto Alegre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Estradiol in people with Gender Dysphoria, run by Hospital de Clinicas de Porto Alegre at 1 site in Brazil.
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 2 inclusion and 7 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 29 Aug 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 Brazil. 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.
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 Maiko Schneider, MD (5551997722606, maikoschneider@hcpa.edu.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Glutamate concentration in the left hippocampus (time frame: 90 days). 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 NCT03651427, which also lists 1 linked publication.
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 29 Aug 2018.