Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001415897
Ethics application status
Approved
Date submitted
11/08/2021
Date registered
20/10/2021
Date last updated
1/12/2021
Date data sharing statement initially provided
20/10/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
The effects of gender affirming hormone therapy on skeletal muscle training and epigenetics
Scientific title
The effects of Gender Affirming hormone therapy on skeletal Muscle training and Epigenetics in transgender individuals: The GAME Study
Secondary ID [1] 304995 0
Nil known
Universal Trial Number (UTN)
Trial acronym
The GAME Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
muscle health and performance 323150 0
body composition 323151 0
metabolic health 323152 0
gender dysphoria 323472 0
Condition category
Condition code
Musculoskeletal 320722 320722 0 0
Normal musculoskeletal and cartilage development and function
Metabolic and Endocrine 320723 320723 0 0
Other endocrine disorders

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This is a prospective matched observational study in adults undergoing gender affirming hormone therapy, and age-matched controls. Participants undergoing gender affirming hormone therapy would have received these therapies regardless of their involvement in the study.

Assessments will take place at three timepoints for adults undergoing gender affirming therapy; prior to beginning gender affirming hormone treatment (baseline) and then at 6 and 12 months into treatment. Age-matched controls will be assessed at baseline and followed up after 12 months. Each timepoint will be divided into three examination days; day one: aerobic fitness tests (1.5-2 hour face-to-face session), day 2: muscle strength assessments (1.5-2 hour face-to-face session), and day three: body composition (DEXA) scans (only conducted at 0 and 12 months) and muscle and blood sampling (1-1.5 hour face-to-face session). Aerobic fitness tests and muscle strength assessments will be conducted by study researchers at Victoria University, with DEXA scans performed by a qualified technician and muscle/blood sampling performed by a medical doctor.
Intervention code [1] 321386 0
Not applicable
Comparator / control treatment
Age-matched cisgender males and females will be recruited and assessed at baseline and 12 months.
Control group
Active

Outcomes
Primary outcome [1] 328542 0
Aerobic fitness measures (composite primary outcome of maximum oxygen uptake consumption (VO2 max), peak aerobic power and lactate threshold), measured through graded exercise (GXT) and maximal oxygen uptake exercise tests.
Timepoint [1] 328542 0
In participants undergoing gender affirming hormone therapy: baseline, 6, 12 months (primary endpoint) into treatment.
In aged-matched participants; baseline and 12 months (primary endpoint)
Primary outcome [2] 328543 0
Muscle strength measures (composite primary outcome; lower body isokinetic and isometric muscle strength) as assessed using knee flexors and extensors and isokinetic dynamometry.
Timepoint [2] 328543 0
In participants undergoing gender affirming hormone therapy: baseline, 6, 12 months (primary endpoint) into treatment.
In aged-matched participants; baseline and 12 months (primary endpoint)
Primary outcome [3] 328588 0
DNA methylation and gene expression profiles in skeletal muscle, assessed using skeletal muscle biopsies and qPCR/RNA sequencing methods and MethylationEPIC arrays.
Timepoint [3] 328588 0
In participants undergoing gender affirming hormone therapy: baseline, 6, 12 months (primary endpoint) into treatment.
In aged-matched participants; baseline and 12 months (primary endpoint)
Secondary outcome [1] 399547 0
Levels of sex hormones, assessed using blood samples and routine pathology tests and standardised techniques.
Timepoint [1] 399547 0
In participants undergoing gender affirming hormone therapy: baseline, 6, 12 months into treatment.
In aged-matched participants; baseline and 12 months.
Secondary outcome [2] 399548 0
Body composition, measured using dual x-ray absorpiometry (DEXA) scans.
Timepoint [2] 399548 0
In participants undergoing gender affirming hormone therapy: baseline and 12 months into treatment.
In aged-matched participants; baseline and 12 months.
Secondary outcome [3] 399549 0
Characteristics of skeletal muscle, examined using skeletal muscle biopsies and standard histological methods
Timepoint [3] 399549 0
In participants undergoing gender affirming hormone therapy: baseline, 6, 12 months into treatment.
In aged-matched participants; baseline and 12 months
Secondary outcome [4] 399550 0
Insulin resistance, assessed as HOMA-IR (fasting glucose x fasting insulin / 22.5), measured from blood samples by routine pathology tests using standardized techniques.
Timepoint [4] 399550 0
In participants undergoing gender affirming hormone therapy: baseline, 6, 12 months into treatment.
In aged-matched participants; baseline and 12 months.
Secondary outcome [5] 399551 0
Genetic variants (in mitochondrial and nuclear DNA) related to response to gender affirming hormone therapy, assessed blood samples and standard PCR techniques.
Timepoint [5] 399551 0
In both participants undergoing gender affirming hormone therapy and aged-matched; 12 months.
Secondary outcome [6] 399554 0
Blood lipid profiles, measured from blood samples by pathology services using standardized methods
Timepoint [6] 399554 0
In participants undergoing gender affirming hormone therapy: baseline, 6, 12 months into treatment.
In aged-matched participants; baseline and 12 months
Secondary outcome [7] 401492 0
Levels of haemoglobin, assessed using blood samples and routine pathology tests and standardised techniques.
Timepoint [7] 401492 0
In participants undergoing gender affirming hormone therapy: baseline, 6, 12 months into treatment.
In aged-matched participants; baseline and 12 months.
Secondary outcome [8] 401495 0
Mitochondrial function, examined using skeletal muscle biopsies and Oroboros instruments.
Timepoint [8] 401495 0
In participants undergoing gender affirming hormone therapy: baseline, 6, 12 months into treatment.
In aged-matched participants; baseline and 12 months
Secondary outcome [9] 401496 0
Skeletal muscle microRNA content, examined using skeletal muscle biopsies and microRNA array cards.
Timepoint [9] 401496 0
In participants undergoing gender affirming hormone therapy: baseline, 6, 12 months into treatment.
In aged-matched participants; baseline and 12 months

Eligibility
Key inclusion criteria
For participants commencing gender affirming hormone therapy:
• Adults aged 18 years and over.
• Willingness to consent and comply with study requirements
• Diagnosed with gender dysphoria who are about to commence gender affirming hormone therapy

For matched cisgender participants:
• Adults aged 18 years and over.
• Willingness to consent and comply with study requirements
• Age-matched to participating individual about to commence gender affirming hormone therapy
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Prior use of gender affirming hormone therapy.
• Prior hypogonadism including previous oophorectomy or orchidectomy.
• Past medical history of cardiovascular conditions, dizziness or fainting during exertion, significant chronic or recurrent respiratory condition, significant neuromuscular, major musculoskeletal problems interfering with ability to cycle, uncontrolled endocrine and metabolic disorders or diabetes requiring insulin and other therapies, infectious blood borne disease, disorders or use of medications that will affect blood clotting and allergies to anaesthetic.
• Active cigarette use.
• Language difficulties.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Sample size calculations:
The study will involve a total of 160 adult participants, comprised of 40 participants over 4 groups (a transgender female and male group, and age-matched cisgender males and female groups). Sample size calculations were based on sex-specific fitness data from the Gene SMART study (n=120), led by listed investigators at Victoria University. For our primary aerobic fitness measure, VO2max, a sample size of 32 per group will be required to detect a difference at 90% power and a 0.05 significance level, based on data for males (mean 48.04, SD; 8.19) and females (mean 42.29, SD; 10.45) from the Gene SMART study. Considering a conservative drop-out rate of ~25%, a target of 40 participants per group (160 in total) was set.

Data analysis plan:
Changes in primary and secondary outcomes will be investigated with linear mixed models that account for repeated measures within the same individuals. We will adjust the models for known confounders (e.g. age, sex) and add an interaction between group and time to ensure that the changes in outcomes are specific to the gender-affirming group. A p value will be considered as significant at a false discovery rate < 0.005.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/01/2022
Actual
Date of last participant enrolment
Anticipated
1/11/2023
Actual
Date of last data collection
Anticipated
1/11/2024
Actual
Sample size
Target
160
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 20224 0
Austin Health - Heidelberg Repatriation Hospital - Heidelberg West
Recruitment postcode(s) [1] 34954 0
3081 - Heidelberg West
Recruitment postcode(s) [2] 34955 0
3011 - Footscray
Recruitment postcode(s) [3] 34956 0
3000 - Melbourne

Funding & Sponsors
Funding source category [1] 309379 0
University
Name [1] 309379 0
Victoria University
Country [1] 309379 0
Australia
Funding source category [2] 309413 0
Other Collaborative groups
Name [2] 309413 0
Trans Health Research Group
Country [2] 309413 0
Australia
Primary sponsor type
University
Name
Victoria University
Address
70/104 Ballarat Rd,
Footscray VIC, 3010
Country
Australia
Secondary sponsor category [1] 310352 0
Hospital
Name [1] 310352 0
Austin Health
Address [1] 310352 0
145 Studley Rd,
Heidelberg VIC 3084
Country [1] 310352 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309195 0
Austin Health Human Research Ethics Commitee
Ethics committee address [1] 309195 0
Ethics committee country [1] 309195 0
Australia
Date submitted for ethics approval [1] 309195 0
07/07/2021
Approval date [1] 309195 0
22/10/2021
Ethics approval number [1] 309195 0
HREC/77146/Austin-2021

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

Contacts
Principal investigator
Name 113306 0
Prof Nir Eynon
Address 113306 0
Victoria University, 70/104 Ballarat Rd, Footscray VIC 3010
Country 113306 0
Australia
Phone 113306 0
+613 9919 5615
Fax 113306 0
Email 113306 0
[email protected]
Contact person for public queries
Name 113307 0
Patrice Jones
Address 113307 0
Victoria University, 70/104 Ballarat Rd, Footscray VIC 3010
Country 113307 0
Australia
Phone 113307 0
+613 9919 5615
Fax 113307 0
Email 113307 0
[email protected]
Contact person for scientific queries
Name 113308 0
Patrice Jones
Address 113308 0
Victoria University, 70/104 Ballarat Rd, Footscray VIC 3010
Country 113308 0
Australia
Phone 113308 0
+613 9919 5615
Fax 113308 0
Email 113308 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All deidentified data collected during the study will be considered on request on a case-by-case basis
When will data be available (start and end dates)?
Start date 06/2022. No end date determined.
Available to whom?
Collaborating researchers with human research ethics committee approval for the proposed analysis
Available for what types of analyses?
All analyses considered on a case-by-case basis.
How or where can data be obtained?
On request to principal investigators, Nir Eynon (email:[email protected]) and Dr Ada Cheung (email: [email protected])


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
13105Other  [email protected] Study protocol to be published in a scientific jou... [More Details]



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.