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Trial registered on ANZCTR


Registration number
ACTRN12623000166673p
Ethics application status
Submitted, not yet 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 Prevention of Muscle Loss After Menopause Using Testosterone: The PAMELA study
Scientific title
Evaluating prevention of Muscle Loss After Menopause Using Testosterone: The PAMELA study
Secondary ID [1] 308952 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Muscle loss 328964 0
Osetopenia 328965 0
sarcopenia 329027 0
osteoporosis 329028 0
Condition category
Condition code
Reproductive Health and Childbirth 325950 325950 0 0
Menstruation and menopause
Musculoskeletal 325952 325952 0 0
Osteoporosis
Musculoskeletal 325953 325953 0 0
Other muscular and skeletal disorders
Metabolic and Endocrine 326011 326011 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Application of active treatment, 1% testosterone cream, 0.5ml (10mg/ml), or placebo cream
applied transdermally daily to upper thigh or lower torso by participant for 6 months.
Compliance will be assessed by collection and weighing of returned cream containers at week 12 and week 26 after commencement of treatment.
Participants will be provided with and asked to self-administer vitamin D3 oral capsule, 1000IU/day for 26 weeks.
Intervention code [1] 325401 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 6 months
Participants will be provided with and asked to self-administer vitamin D3 oral capsule, 1000IU/day for 26 weeks.
Control group
Placebo

Outcomes
Primary outcome [1] 333801 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] 333801 0
6 months post-randomisation.
Secondary outcome [1] 418339 0
Any change in grip force measured via the Leonardo Mechanography Ground Reaction Force Platform.
Timepoint [1] 418339 0
6 months post-randomisation.
Secondary outcome [2] 418340 0
Any change in whole body composition assessed using dual-energy X-ray absorptiometry (DXA).
Timepoint [2] 418340 0
6 months post-randomisation.
Secondary outcome [3] 418342 0
Any change in health-related quality of life assessed using the Short-Form 36 questionnaire.
Timepoint [3] 418342 0
6 months post-randomisation.
Secondary outcome [4] 418572 0
Any change in grip work (endurance) measured via the Leonardo Mechanography Ground Reaction Force Platform.
Timepoint [4] 418572 0
6 months post-randomisation.
Secondary outcome [5] 418573 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] 418573 0
6 months post-randomisation.
Secondary outcome [6] 418574 0
Any change in power assessed via the heel rise test measured via the Leonardo Mechanography Ground Reaction Force Platform.
Timepoint [6] 418574 0
6 months post-randomisation.
Secondary outcome [7] 418575 0
Any change in bone mineral density assessed using using DXA scans
Timepoint [7] 418575 0
6 months post-randomisation.
Secondary outcome [8] 418576 0
Any change in menopause-related quality of life assessed using the MENQOL questionnaire.
Timepoint [8] 418576 0
6 months post-randomisation.

Eligibility
Key inclusion criteria
Naturally postmenopausal women, aged 55-70 years, who are not taking medications that might influence hormone levels or muscle/bone health. Participants must be agreeable to taking vitamin D3 1000 IU/day and making no meaningful change in their exercise regime or diet over the course of the study. Participants will be required to have a body mass index between 18 and 35 kg/m2, a clinically acceptable mammogram in the preceding 2 years and clinically acceptable cervical screening test results within the preceding 5 years.
Minimum age
55 Years
Maximum age
70 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Body mass index <18 or >35 kg/m2
2. Current or recent (in the past 12 months) use of systemic estrogen replacement therapy or tibolone (vaginal estrogen permitted)
3. Current or recent (in the past 12 months) use of antiandrogens
4. Use of any drugs affecting bone metabolism such as bisphosphonates, denosumab, systemic corticosteroids, antineoplastic drugs, thiazide diuretics, anti-epileptic drugs, and heparin in the last 5 years
5. History of testosterone or dehydroepiandrosterone treatment in the last 5 years
6. Plans to commence a weight reduction diet for the duration of the study
7. Known allergy to almonds (a constituent of the cream)
8. Severe chronic skin disease (such as eczema or psoriasis) that is likely to interfere with transdermal drug absorption
9. Intolerance to transdermal testosterone
10. Clinically significant infection requiring systemic antibiotics
11. Undiagnosed vaginal bleeding
12. Evidence of clinical hyperandrogenism (hirsutism, androgenic alopecia, or acne) as assessed by the recruiting clinician
13. Taking herbal remedies, grapefruit juice, or medications known to be strong inducers or inhibitors of cytochrome P450 3A4 or known to interact with testosterone metabolism or reproductive hormone levels.
14. Use of protein supplementation is permitted but participants will be restricted from commencing new any new protein supplement or increasing their consumption.
15. History of smoking within the past year, active substance abuse, or alcohol consumption of more than two standard drinks per day
16. Severe musculoskeletal, neurological, or metabolic disease which might influence the results of the study
17. Present or previous systemic cancer diagnosis in the last 5 years
18. Donation of blood within the last 6 weeks or plasma within 7 days of the first dosing in this study
19. Abnormal thyroid function (abnormal thyroid stimulating hormone (TSH) value confirmed by a free T4 outside laboratory range)
20. Being considered by a chief investigator to be unsuitable for participation in the study

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 is concealed by central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Allocation of participants in a 1:1 ratio to either transdermal testosterone or placebo group will be based on computer generated random numbers prepared by a statistician with no involvement in the trial. Randomization will be performed based on blocks of size 4 and 6, and stratified based on whether participants meet the current Australian guidelines for physical activity (>150 minutes moderate intensity or >75 minutes vigorous intensity exercise per week).
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
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis
An intention-to-treat analysis, including all participants in their randomized groups regardless of their adherence to assigned treatments, will be performed in a blinded fashion. Differences between randomized groups in the changes in primary and secondary outcome measures at 26 weeks will be examined using linear mixed-effects regression models with baseline value as the covariate, fixed factors for treatment, time, and treatment x time interaction, and with an autoregressive AR(1) covariance matrix for repeated measures of individuals over time. If >5% of participants are missing their primary outcome, multiple imputation will be applied to account for missing data, with missing values imputed separately by treatment group, assuming data are missing at random. The bootstrap approach will be used to provide 95% confidence intervals and p-values if the normality assumption is questionable. Additional adjustment will be carried out in a sensitivity analysis if clinically important baseline imbalances between randomized groups are identified. Pre-specified subgroup analyses will be performed by testing a treatment by subgroup interaction in the models. Per-protocol analyses for the primary and secondary endpoints will be conducted as secondary analyses.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
3/04/2023
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
156
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 313166 0
Government body
Name [1] 313166 0
National Health and Medical Research Council
Country [1] 313166 0
Australia
Primary sponsor type
University
Name
Monash University
Address
School of Public Health and Preventive Medicine
Monash University
553 St Kilda Rd
Melbourne, VIC 3004
Country
Australia
Secondary sponsor category [1] 314872 0
None
Name [1] 314872 0
Address [1] 314872 0
Country [1] 314872 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 312407 0
Monash University Human Ethics Committee
Ethics committee address [1] 312407 0
Ethics committee country [1] 312407 0
Australia
Date submitted for ethics approval [1] 312407 0
01/02/2023
Approval date [1] 312407 0
Ethics approval number [1] 312407 0

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

Contacts
Principal investigator
Name 124550 0
Prof Susan Davis
Address 124550 0
The Women’s Health Research Program,
School of Public Health and Preventive Medicine
Monash University
553 St Kilda Rd,
Melbourne, Victoria 3004
Country 124550 0
Australia
Phone 124550 0
+61 3 9903 0827
Fax 124550 0
+61 3 9903 0828
Email 124550 0
susan.davis@monash.edu
Contact person for public queries
Name 124551 0
Susan Davis
Address 124551 0
The Women’s Health Research Program,
School of Public Health and Preventive Medicine
Monash University
553 St Kilda Rd,
Melbourne, Victoria 3004
Country 124551 0
Australia
Phone 124551 0
+61 3 9903 0827
Fax 124551 0
+61 3 9903 0828
Email 124551 0
susan.davis@monash.edu
Contact person for scientific queries
Name 124552 0
Susan Davis
Address 124552 0
The Women’s Health Research Program,
School of Public Health and Preventive Medicine
Monash University
553 St Kilda Rd,
Melbourne, Victoria 3004
Country 124552 0
Australia
Phone 124552 0
+61 3 9903 0827
Fax 124552 0
+61 3 9903 0828
Email 124552 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
18304Study 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.