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Trial registered on ANZCTR


Registration number
ACTRN12623000165684
Ethics application status
Approved
Date submitted
8/02/2023
Date registered
17/02/2023
Date last updated
17/02/2023
Date data sharing statement initially provided
17/02/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluating Testosterone Therapy to Prevent Heart Failure in Women: The ETHEL study.
Scientific title
Evaluating Testosterone Therapy to Prevent Heart Failure in Women: The ETHEL study.
Secondary ID [1] 308951 0
None
Universal Trial Number (UTN)
Trial acronym
ETHEL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stage B heart failure with preserved ejection fraction 328963 0
Condition category
Condition code
Reproductive Health and Childbirth 325948 325948 0 0
Menstruation and menopause
Cardiovascular 326010 326010 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a randomised double-blind placebo-controlled crossover study. Participants will receive either treatment or placebo for 4 months, then receive the alternative study drug for 4 months with a 4-week washout period in between each 4-month treatment cycle. The total duration of participation in this study is 9 months.

Application of active treatment, 1% testosterone cream, 0.5ml (10mg/ml), or placebo cream
applied transdermally daily to upper thigh or buttock by participant for 4 months.
Compliance will be assessed by collection and weighing of returned cream containers at end of treatment period.
Intervention code [1] 325396 0
Treatment: Drugs
Comparator / control treatment
Placebo is unmedicated Androfeme 1 base formulation cream containing dl-8- tocopherol acetate (vitamin E), almond oil, butylated hydroxytoluene, carbomer 940, cetomacrogol 1000, cetostearyl alcohol, citric acid -anhydrous, triethanolamine, water purified and Phenonip® - a preservative containing hydroxybenzoates and phenoxyethanol.0.5ml daily applied transdermally to upper thigh or buttock for 4 months.
Control group
Placebo

Outcomes
Primary outcome [1] 333800 0
The primary outcome will be any change in cardiorespiratory fitness, assessed by change in VO2peak during cardiopulmonary exercise testing (CPET) on a cycle ergometer.
Timepoint [1] 333800 0
Change will be measured at 4 months post randomisation (at the conclusion of first treatment phase). It will then be measured both before and after the second phase of treatment (i.e. at 5 and 9 months post randomisation).
Secondary outcome [1] 418338 0
Any change in body-weight corrected power (W/kg) during a two leg countermovement jump measured via the Leonardo Mechanography Ground Reaction Force Platform.
Timepoint [1] 418338 0
Change will be measured at 4 months post randomisation (at the conclusion of first treatment phase). It will then be measured both before and after the second phase of treatment (i.e. at 5 and 9 months post randomisation).
Secondary outcome [2] 418558 0
Any change in body-weight corrected power (W/kg) during a two leg countermovement jump measured via the Leonardo Mechanography Ground Reaction Force Platform.
Timepoint [2] 418558 0
Change will be measured at 4 months post randomisation (at the conclusion of first treatment phase). It will then be measured both before and after the second phase of treatment (i.e. at 5 and 9 months post randomisation).
Secondary outcome [3] 418559 0
Any change in grip force measured via the Leonardo Mechanography Ground Reaction Force Platform.
Timepoint [3] 418559 0
Change will be measured at 4 months post randomisation (at the conclusion of first treatment phase). It will then be measured both before and after the second phase of treatment (i.e. at 5 and 9 months post randomisation).
Secondary outcome [4] 418560 0
Any change in grip work (endurance) measured via the Leonardo Mechanography Ground Reaction Force Platform.
Timepoint [4] 418560 0
Change will be measured at 4 months post randomisation (at the conclusion of first treatment phase). It will then be measured both before and after the second phase of treatment (i.e. at 5 and 9 months post randomisation).
Secondary outcome [5] 418564 0
Any change in measures of balance (standing with feet together eyes open/closed, tandem stance eyes open/closed, single leg stance eyes open/closed) measured via stabilometry on the Leonardo Mechanography Ground Reaction Force Platform.
Timepoint [5] 418564 0
Change will be measured at 4 months post randomisation (at the conclusion of first treatment phase). It will then be measured both before and after the second phase of treatment (i.e. at 5 and 9 months post randomisation).
Secondary outcome [6] 418565 0
Any change in power during the heel rise test measured via the Leonardo Mechanography Ground Reaction Force Platform.
Timepoint [6] 418565 0
Change will be measured at 4 months post randomisation (at the conclusion of first treatment phase). It will then be measured both before and after the second phase of treatment (i.e. at 5 and 9 months post randomisation).
Secondary outcome [7] 418566 0
Any change in ventricular structure or function assessed by echocardiogram.
Timepoint [7] 418566 0
Change will be measured at 4 months post randomisation (at the conclusion of first treatment phase). It will then be measured both before and after the second phase of treatment (i.e. at 5 and 9 months post randomisation).
Secondary outcome [8] 418567 0
Any change in cardiac structure, function, mass, or ventricular remodelling assessed by cardiac magnetic resonance imaging.
Timepoint [8] 418567 0
Change will be measured at 4 months post randomisation (at the conclusion of first treatment phase). It will then be measured both before and after the second phase of treatment (i.e. at 5 and 9 months post randomisation).
Secondary outcome [9] 418568 0
Any change in serum sex steroid levels (testosterone, estradiol, estrone, dehydroepiandrosterone, dihydrotestosterone).
Timepoint [9] 418568 0
Change from baseline will be measured both before and after the second phase of treatment (i.e. at 5 and 9 months post randomisation).
Secondary outcome [10] 418569 0
Change in overall health status as measured via the short-form 36 questionnaire.
Timepoint [10] 418569 0
Change will be measured at 4 months post randomisation (at the conclusion of first treatment phase). It will then be measured both before and after the second phase of treatment (i.e. at 5 and 9 months post randomisation).
Secondary outcome [11] 418570 0
Change in well-being as measured by the psychological general well-being index.
Timepoint [11] 418570 0
Change will be measured at 4 months post randomisation (at the conclusion of first treatment phase). It will then be measured both before and after the second phase of treatment (i.e. at 5 and 9 months post randomisation).
Secondary outcome [12] 418571 0
Change in physical activity and sedentary behaviours, measured over 7 days via a hip-worn accelerometer & activity log.
Timepoint [12] 418571 0
Change will be measured at 4 months post randomisation (at the conclusion of first treatment phase). It will then be measured both before and after the second phase of treatment (i.e. at 5 and 9 months post randomisation).

Eligibility
Key inclusion criteria
- Evidence of Stage B heart failure with reduced functional capacity (<85% age-predicted VO2peak).
- Normal mammogram within the preceding 2 years
Minimum age
60 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Heart failure, either documented or undiagnosed with an EF <40% or NTproBNP >400ng/L
- Other cardiac disease (myocardial infarction, angina; known coronary artery disease; valve disease more than moderate)
- Features incompatible with the study design (unlikely to be adherent to follow-up; <12 months life expectancy due to concomitant disease; participation in another clinical trial where blinded treatment would be unacceptable; unable to provide written informed consent)
- Inability to acquire interpretable echo images (uncommon)
- Unstable diabetes (HbA1C>7.5%)
- Estrogen-sensitive cancer
- Use of any drugs or dietary supplements that may affect testosterone effects including, but not limited to systemic antiandrogen therapy (spironolactone; cyproterone acetate; finasteride; minoxidil)
- Treatment with SGLT-2 inhibitors or GLP-1 agonists as indicated
- Recent use of androgen therapy
- Contraindication to exercise
- Inability to speak or understand English

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)
Participants will be randomly allocated to treatment with testosterone or identical placebo in a 1:1 ratio. This will be based on computer generated random numbers prepared by a statistician with no involvement in the trial. The use of a central automated allocation procedure with security in place will ensure the allocation cannot be accessed or influenced by any person. The investigators and participants will be blinded to study drug assignment and the blind will be maintained until the database is closed. Study drug identity will be concealed by packaging. AndroFeme1 and placebo cream will be in identical packaging. Emergency unblinding will be allowed in limited situations that impact on the safety of study participants.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Allocation will be based on computer generated random numbers prepared by a statistician with no involvement in the trial.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
6/03/2023
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
38
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 313165 0
Charities/Societies/Foundations
Name [1] 313165 0
The Heart Foundation
Country [1] 313165 0
Australia
Primary sponsor type
University
Name
Monash University
Address
Wellington Road
Clayton
Victoria 3800
Country
Australia
Secondary sponsor category [1] 314871 0
None
Name [1] 314871 0
Address [1] 314871 0
Country [1] 314871 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312406 0
Monash University Human Ethics Committee
Ethics committee address [1] 312406 0
Ethics committee country [1] 312406 0
Australia
Date submitted for ethics approval [1] 312406 0
15/12/2022
Approval date [1] 312406 0
11/01/2023
Ethics approval number [1] 312406 0
36621

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

Contacts
Principal investigator
Name 124546 0
Prof Susan Davis
Address 124546 0
The Women’s Health Research Program,
School of Public Health and Preventive Medicine
Monash University
553 St Kilda Rd,
Melbourne, Victoria 3004
Country 124546 0
Australia
Phone 124546 0
+61 3 9903 0827
Fax 124546 0
Email 124546 0
susan.davis@monash.edu
Contact person for public queries
Name 124547 0
Susan Davis
Address 124547 0
The Women’s Health Research Program,
School of Public Health and Preventive Medicine
Monash University
553 St Kilda Rd,
Melbourne, Victoria 3004
Country 124547 0
Australia
Phone 124547 0
+61 3 9903 0827
Fax 124547 0
Email 124547 0
susan.davis@monash.edu
Contact person for scientific queries
Name 124548 0
Susan Davis
Address 124548 0
The Women’s Health Research Program,
School of Public Health and Preventive Medicine
Monash University
553 St Kilda Rd,
Melbourne, Victoria 3004
Country 124548 0
Australia
Phone 124548 0
+61 3 9903 0827
Fax 124548 0
Email 124548 0
susan.davis@monash.edu

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?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
18303Study protocol  susan.davis@monash.edu



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.