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Trial registered on ANZCTR


Registration number
ACTRN12619001691134p
Ethics application status
Not yet submitted
Date submitted
25/11/2019
Date registered
2/12/2019
Date last updated
2/12/2019
Date data sharing statement initially provided
2/12/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Testosterone to treat men with painful osteoarthritis of the knee
Scientific title
A randomised, double-blind, placebo-controlled, parallel group study to determine whether Testosterone treatment on a background of exercise improves physical function, pain and body composition in men with OsteoArthritis of the Knee (TEX-OAK)
Secondary ID [1] 299912 0
None
Universal Trial Number (UTN)
Trial acronym
TEX-OAK
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Knee Osteoarthritis 315334 0
Condition category
Condition code
Musculoskeletal 313638 313638 0 0
Osteoarthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Study type
A pilot randomised controlled trial (RCT) to test whether addition of testosterone to usual care (exercise rehabilitative program) will improve function, pain and muscle strength in N=30 men with significant knee OA. The trial will be conducted in fully double-blind fashion with a 12 week duration. Randomisation will be completed by Lawley pharmaceuticals. Outcomes will be addressed at baseline (week 0) and end-of study (week 12)

Procedures
Medical assessments will be performed at IIID (Murdoch University) By Tarryn Sohn (medical registrar) with supervision from Dr Helen Keen (rheumatologist), Prof Bu Yeap (endocrinologist), Merrilee Needham (neurologist)

Drugs applied
Active name: testosterone
Trade name: AndroForte 5, transdermal cream, 100mg in 2 mls applied once daily by the patient over a 12 week period

Placebo: the placebo contains exactly the same ingredients as the active (minus the testosterone) exercise training
The exercise program will comprise 5 supervised sessions (1 hour each) within Murdoch Universities’ gymnasium over the 12 week period, and a supervised home-based exercise program.

Exercise training
The exercise program will be individually prescribed and progressed to accommodate the large variance in functional capabilities of each participant expected at baseline and in their individual exercise-response. Training variables will be modified according to exercise type, duration, frequency (based on pain and recovery) and intensity of the exercise. Resistance exercise will largely be conducted using multi-joint compound exercises of the lower limbs using body-weight and elastic bands (Therabands); with varying levels of resistance providing the different intensities (different colour bands). The initial exercise prescription will occur following baseline assessment. Progression of exercises and intensity will be based on rating of perceived exertion (RPE; a subjective scale) scores provided during fortnightly telephone calls and supervisory visits.

Home-based program
The Home-based progressive exercise will comprise of resistance, aerobic/ mobility, and balance exercises. All exercises will comprise of either resistance bands (therabands) or body weight movements. Resistance bands will largely be single-joint exercises while body weight movements will target movements involved in mobility and function, however focus will be on knee extensors and stabilisers. This will be supplemented with aerobic/ mobility and functional exercises (i.e. walking, sitting and rising) and balance exercises (ie narrow stance, tandem stance). The duration of the exercise program will be approximately 30 minutes which will be completed at least three times a week.

The home-based exercise program will be completed only at home by participants for the intervention period. The program will be supervised via telephone and home visits. All exercise sessions will be monitored via an exercise-based log-book which will include information regarding the rating of perceived exertion scale.

The participants will be asked to keep a record on a diary of their drug application, exercise and pain levels (using the visual analogue scale prior to exercise session). Additionally, all analgesia used will be recorded in patient’s diaries.

Procedure timeline
Medical assessments: screening, baseline and end of study
Blood collection: screening, week 0 and week 12
Intervention code [1] 316186 0
Treatment: Drugs
Comparator / control treatment
The transdermal cream will be applied onto an area of the torso with low subcutaneous fat, and then covered

This is a double-blinded RCT where participants will be randomly assigned to a group receiving placebo or testosterone.. Exercise training will be performed regardless of the treatment received.

The placebo contains exactly the same ingredients as the active (minus the testosterone). .
Control group
Placebo

Outcomes
Primary outcome [1] 322078 0
Primary outcome: Physical function as assessed in performance based tests. Specifically
- 30-s chair-stand test
- 40m fast paced walk test
- Stair climb test
- Timed up and go test
- 6 minute walk test
Timepoint [1] 322078 0
Time points: function will be measured as above at week 0 and week 12
Secondary outcome [1] 377243 0
Pain
Timepoint [1] 377243 0
As recorded in individualised patient diaries
Change in knee pain (total WOMAC pain, weight bearing and non–weight bearing pain), all time points.
Assessed at each visit using a visual analogue scale
Secondary outcome [2] 377244 0
Muscle strength
Timepoint [2] 377244 0
Dynamometry in the lower limbs (involving both lower limbs simultaneously) at weeks 0 and 12 (mainly measures quadriceps and hip flexors which are important muscle groups for knee OA)

Eligibility
Key inclusion criteria
Key inclusion criteria adult men with significant knee OA in accordance with ACR guidelines who are able to provide informed consent
Inclusion criteria
- Aged 40-74 years
- Men with significant knee pain on most days (defined as VAS>40mm)
- Meet American College of Rheumatology (ACR) clinical criteria for knee OA confirmed by a rheumatologist
- Baseline testosterone less than or equal to 14nmol/L
Minimum age
40 Years
Maximum age
74 Years
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria
- Major knee surgery within the last 3 months
- Major knee trauma/ significant knee injury within the last 6 months
- Arthroscopy or open surgery in the index knee in the last 12 months
- Injections of corticosteroids (last 3 months) or hyaluronic acid (last 6 months)
- Organic hypogonadism
- History of prostate cancer
- Suspected malignancy on DRE
- Elevated PSA
- Elevated haematocrit
- Other forms of inflammatory arthritis
- Active cardiovascular disease (unstable angina, myocardial infarction, stroke, transient ischaemic attack, or revascularisation procedure within the past 12 months)
- Other major co-morbidity (eg advanced lung disease or cancer)
- Use of androgens or anti-androgen drugs in past 12 months
- Untreated hypertension

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
This pilot randomised controlled trial (RCT) will have a limited number of participants (n=30) and will therefore be unlikely to allow comprehensive inferential analysis. Data will be used to establish the feasibility, including safety and tolerability of running a national full-scale RCT of testosterone in men with painful knee OA.

Random-intercept linear mixed models will be generated for outcomes (modelled as fixed-effects) of interest and estimated margin means generated. The primary outcome will be within (pre, post)-between (T, Placebo) interaction which will be assessed using unadjusted analysis (LSD). For each outcome, effect size calculations and clinically meaningful changes will be conducted/ assessed to inform future trials. Bivariate associations between outcome measure change-scores and variables of interest (i.e., age, baseline score) using either a Pearson’s or Spearman rank test.

Statistical analysis will be performed with the assistance of a biostatistician at IIID.

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

Funding & Sponsors
Funding source category [1] 304371 0
Government body
Name [1] 304371 0
Research Development Unit, Department of Health
Address [1] 304371 0
189 Royal St, Perth WA 6004
Country [1] 304371 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Lawley Pharmaceuticals Pty Ltd
Address
2/15A Harrogate Street
West Leederville
WA 6007
Country
Australia
Secondary sponsor category [1] 304624 0
None
Name [1] 304624 0
Address [1] 304624 0
Country [1] 304624 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 304812 0
Human Research Ethics Committee - Murdoch University
Ethics committee address [1] 304812 0
Murdoch University
Chancellery Building Room 1.006
South Street, Murdoch
Western Australia 6150
Ethics committee country [1] 304812 0
Australia
Date submitted for ethics approval [1] 304812 0
02/12/2019
Approval date [1] 304812 0
Ethics approval number [1] 304812 0

Summary
Brief summary
Knee OA is a major contributor to the global burden of disease, associated with significant pain, physical dysfunction and reduced quality of life. Muscle weakness and decreased lower limb muscle mass are common in knee OA, and are associated with poor long term outcomes.

Therapy that builds muscle mass and improves physical function offers a new avenue to improve patient outcomes. Testosterone is the classical anabolic steroid hormone, which increases muscle mass and strength in men. However, it has never been tested as an intervention in men with knee OA.

This pilot RCT in men with knee OA, will test the hypothesis that testosterone therapy will increase physical function, reduce pain and increase leg strength.

The study will be completed in a randomised, double-blind fashion. The investigators have expertise in rheumatology, endocrinology, neurology and physical sciences
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 98286 0
Prof Prof Merrilee Needham
Address 98286 0
Institute for Immunology and Infectious Diseases
Murdoch University
Building 390 Discovery Way
Murdoch WA 6150
Country 98286 0
Australia
Phone 98286 0
+61 8 9360 1334
Fax 98286 0
+61 8 9360 1380
Email 98286 0
Merrilee.Needham@health.wa.gov.au
Contact person for public queries
Name 98287 0
Dr Tarryn Sohn
Address 98287 0
Fiona Stanley Hospital
11 Robin Warren Dr, Murdoch WA 6150
Country 98287 0
Australia
Phone 98287 0
+61 8 6152 2222
Fax 98287 0
Email 98287 0
tarryn.sohn@health.wa.gov.au
Contact person for scientific queries
Name 98288 0
Dr Tarryn Sohn
Address 98288 0
Fiona Stanley Hospital
11 Robin Warren Dr, Murdoch WA 6150
Country 98288 0
Australia
Phone 98288 0
+61 8 6152 2222
Fax 98288 0
Email 98288 0
tarryn.sohn@health.wa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The data set is kept on local secure servers. Data sharing requests can be submitted to the research team.
It is not intended to share IPD for the trial. Results will be made available as per open access requirements.
What supporting documents are/will be available?
No other documents available
Summary results
No Results