Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624001337561
Ethics application status
Approved
Date submitted
20/09/2024
Date registered
4/11/2024
Date last updated
4/11/2024
Date data sharing statement initially provided
4/11/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Low-dose testosterone treatment in trans individuals
Scientific title
Effects of Low-Dose Testosterone on Mental and Physical Health Outcomes in Trans Individuals
Secondary ID [1] 312998 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Transgender health 335186 0
Gender dysphoria 335187 0
Depression 335188 0
Suicide 335189 0
Condition category
Condition code
Metabolic and Endocrine 331675 331675 0 0
Other endocrine disorders
Mental Health 331676 331676 0 0
Depression
Mental Health 331677 331677 0 0
Suicide

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Transdermal testosterone 1%, transdermal gel, 12.5mg per pump actuation, 2 pump actuations daily, from week 0 to week 12. Adherence monitored through patient calendar/ diary.
Followed by a 12-month extended follow-up post-initiation of testosterone.
Intervention code [1] 329539 0
Treatment: Drugs
Comparator / control treatment
Currently, in our Austin Health gender clinic, following initial assessment of suitability and informed consent, due to large demand for appointments, there is a minimum 3-month waitlist prior to initiation of gender affirming hormone therapy. This is standard care.
We will undertake a pragmatic intervention whereby after initial assessment and informed consent, we will randomise individuals to immediate low-dose testosterone therapy or delayed testosterone therapy (commencement of low-dose testosterone after standard care 3-month waiting list). This will be followed by a 12-month extended follow-up post-initiation of testosterone.

Semi-structured interviews will be conducted with the first 15 participants who opt-in to the interview, 6 months after commencing testosterone.
Control group
Active

Outcomes
Primary outcome [1] 339401 0
Symptoms of gender dysphoria
Timepoint [1] 339401 0
Baseline, 3 months (primary timepoint), 6 months and 12 months after intervention commencement
Primary outcome [2] 339402 0
Gender Euphoria
Timepoint [2] 339402 0
Baseline, 3 months (primary timepoint), 6 months, 12 months after intervention commencement.
Primary outcome [3] 339403 0
Psychological distress
Timepoint [3] 339403 0
Baseline, 3 months (primary timepoint), 6 months, 12 months after intervention commencement
Secondary outcome [1] 439790 0
Suicidality
Timepoint [1] 439790 0
Baseline, 3 months, 6 months, 12 months after intervention commencement
Secondary outcome [2] 439791 0
Quality of Life
Timepoint [2] 439791 0
Baseline, 3 months, 6 months, 12 months after intervention commencement
Secondary outcome [3] 439792 0
Serum total testosterone concentration
Timepoint [3] 439792 0
Baseline, 3 months, 6 months, 12 months after intervention commencement
Secondary outcome [4] 439793 0
Haemoglobin/ haematocrit level
Timepoint [4] 439793 0
Baseline, 3 months, 6 months, 12 months after intervention commencement
Secondary outcome [5] 439794 0
Biochemistry: creatinine
Timepoint [5] 439794 0
Baseline, 3 months, 6 months, 12 months after intervention commencement
Secondary outcome [6] 439795 0
Biochemistry: estimated glomerular filtration rate
Timepoint [6] 439795 0
Baseline, 3 months, 6 months, 12 months after intervention commencement
Secondary outcome [7] 439796 0
Biochemistry: liver function tests
Timepoint [7] 439796 0
Baseline, 3 month, 6 months and 12 months after intervention commencement
Secondary outcome [8] 439797 0
Biochemistry: glucose
Timepoint [8] 439797 0
Baseline and 12 months after intervention commencement
Secondary outcome [9] 439798 0
Biochemistry: lipid profile
Timepoint [9] 439798 0
Baseline and 12 months after intervention commencement
Secondary outcome [10] 439799 0
Semi-structured interviews - with subgroup of participants, measuring gender dysphoria, gender euphoria and mental health. This will be assessed as a composite outcome.
Timepoint [10] 439799 0
6 months after intervention commencement

Eligibility
Key inclusion criteria
Trans people newly commencing low-dose testosterone, who:
1. Are deemed suitable for commencement using the informed consent model of care, and
2. Plan to remain on low-dose testosterone for at least 3 months (from the time of
enrolment in the trial)
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Contraindication to testosterone
2. Previous testosterone treatment
3. Significant mental health conditions or cognitive impairment compromising the ability to
provide informed consent

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation performed by third party off site using schedule
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
Power calculation is based on the primary and secondary endpoints of gender dysphoria and depression, using change in GPSQ and PHQ-9 over 3 months following commencement of full-dose testosterone from our previous RCT (Nolan et al., 2023).
For gender dysphoria, the sample size required with a level of significance of 0.05 and power of 0.9 to demonstrate a similar magnitude of change in GPSQ, when the mean GPSQ decreased from 46.2±6.0 to 38.0±6.2 after 3 months of testosterone, and assumption that GPSQ will not change in individuals allocated to standard care, is 11 per group.
For depression, the sample size required with a level of significance of 0.05 and power of 0.9 to demonstrate a change in PHQ-9 of 5 or more, when the mean PHQ-9 at baseline was 15.2±4.7, and assumption that PHQ-9 will not change in individuals allocated to standard care, is 19 per group.
We will recruit 24 individuals per group to allow for 20% attrition.

Descriptive statistics at baseline will be presented as mean (SD) or median (IQR) as appropriate for continuous variables, and frequency (%) for categorical variables.
Chi-squared tests will be used to compare the proportion of participants with clinically significant changes in outcome measures. Longitudinal changes in outcome measures will be assessed using a linear mixed-effects model with group, time, age (as a stratification variable) and an interaction between group and time. A random intercept will be fitted for each participant. Pre-defined post-hoc contrasts will be used to estimate the mean difference and corresponding 95% confidence interval between the intervention group and the standard care group across time. A two-tailed significance level of p<0.05 will be used.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
11/11/2024
Actual
Date of last participant enrolment
Anticipated
30/03/2026
Actual
Date of last data collection
Anticipated
14/04/2027
Actual
Sample size
Target
48
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 27112 0
Austin Health - Heidelberg Repatriation Hospital - Heidelberg West
Recruitment postcode(s) [1] 43190 0
3081 - Heidelberg West

Funding & Sponsors
Funding source category [1] 317438 0
Charities/Societies/Foundations
Name [1] 317438 0
Royal Australasian College of Physicians-Endocrine Society of Australia
Country [1] 317438 0
Australia
Primary sponsor type
University
Name
University of Melbourne
Address
Country
Australia
Secondary sponsor category [1] 319728 0
None
Name [1] 319728 0
Address [1] 319728 0
Country [1] 319728 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316156 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 316156 0
Ethics committee country [1] 316156 0
Australia
Date submitted for ethics approval [1] 316156 0
28/06/2024
Approval date [1] 316156 0
01/10/2024
Ethics approval number [1] 316156 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 136966 0
Dr Brendan Nolan
Address 136966 0
Level 2, Centaur Building Heidelberg Repatriation Hospital 300 Waterdale Road Heidelberg Heights VIC 3081
Country 136966 0
Australia
Phone 136966 0
+61 394962260
Fax 136966 0
Email 136966 0
nolan.b@unimelb.edu.au
Contact person for public queries
Name 136967 0
Dr Brendan Nolan
Address 136967 0
Level 2, Centaur Building Heidelberg Repatriation Hospital 300 Waterdale Road Heidelberg Heights VIC 3081
Country 136967 0
Australia
Phone 136967 0
+61 394962260
Fax 136967 0
Email 136967 0
gender-research@unimelb.edu.au
Contact person for scientific queries
Name 136968 0
Dr Brendan Nolan
Address 136968 0
Level 2, Centaur Building Heidelberg Repatriation Hospital 300 Waterdale Road Heidelberg Heights VIC 3081
Country 136968 0
Australia
Phone 136968 0
+61 394962260
Fax 136968 0
Email 136968 0
gender-research@unimelb.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.