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Trial registered on ANZCTR


Registration number
ACTRN12613001219774
Ethics application status
Approved
Date submitted
31/10/2013
Date registered
6/11/2013
Date last updated
3/07/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Head Injury and Testosterone
Scientific title
A 12-month, double-blind, randomised, placebo-controlled clinical trial to determine the efficacy of multiple-dose testosterone undecanoate administration on neuropsychological, psychosocial and biological markers (biomarkers) in male participants with traumatic brain injury.
Secondary ID [1] 282434 0
Nil known.
Universal Trial Number (UTN)
Trial acronym
HIT Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Traumatic Brain Injury 289040 0
Condition category
Condition code
Neurological 289383 289383 0 0
Other neurological disorders
Injuries and Accidents 290817 290817 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will receive either testosterone undecanoate intramuscular injection (REANDRON 'Registered Trademark' 1000mg/4ml solution) or placebo at 8-week intervals for 48-weeks, with initial administration occurring within 3-months of traumatic brain injury. Ampoules of REANDRON 'Registered Trademark' and matching placebo will be supplied by Bayer-Schering, Australia.
Intervention code [1] 287078 0
Treatment: Drugs
Comparator / control treatment
The placebo ampoules will match the REANDRON 'Registered Trademark' vials in appearance and content to maintain blinding. Placebo testosterone will be presented in an identical 5 ml glass ampoule and has similar appearance as a clear, yellowish oily solution. Ingredients include benzyl benzoate and castor oil. Bayer Australia Limited will supply the matching placebo ampoules.
Control group
Placebo

Outcomes
Primary outcome [1] 289488 0
To examine the cognitive and behavioural effects of the intervention compared to placebo, both objective tests and behavioural rating scales will be utilised. The primary outcome measures for this trial include the Mini Mental State Examination, Rey Auditory Verbal Learning Test, WAIS-III Digit Span, WAIS-III Digit Symbol Test, and Controlled Oral Word Association Test. The primary behavioural rating scale includes the Frontal Systems Behavior Scale, both patient and informant versions.
Timepoint [1] 289488 0
Approximately 12 months from initial treatment administration
Primary outcome [2] 289489 0
To evaluate the blood and brain biomarkers associated with Alzheimer’s disease, and neuroinflammation in the intervention and placebo groups. This primary outcome assesses the change-from-baseline in biomarkers including the brain beta-amyloid burden, as measured by amyloid PET, plasma beta-amyloid, and inflammatory and oxidative markers.
Timepoint [2] 289489 0
Approximately 12 months from initial treatment administration
Secondary outcome [1] 302620 0
To examine the psychosocial outcomes of the intervention when compared to placebo, the Mayo-Portland Adaptability Inventory, both patient and informant versions will be used.
Timepoint [1] 302620 0
Approximately 12 months from initial treatment administration.
Secondary outcome [2] 305350 0
To examine participant quality of life after the intervention, the Epworth Sleepiness Scale and the Quality of life after Brain Injury will be used.
Timepoint [2] 305350 0
Approximately 12 months from initial treatment administration.

Eligibility
Key inclusion criteria
Male;
Aged 20 to 65 years old;
Brain injured with a severity of moderate to severe on admission Glasgow Coma Scale (GCS score of 7 to 12);
Able to personally read and understand the Participant Information and Consent Form, and provide written, signed and dated informed consent to participate in study;
Having been discharged from acute-care hospital stay and able to receive an initial injection within 3 months of injury;
Able and willing to meet all protocol-required procedures and visits.
Minimum age
20 Years
Maximum age
65 Years
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Previous or ongoing chronic or recurrent disease of the central nervous system or psychiatric disease that may have an impact on cognitive performance (e.g. Bipolar disorder, Dementia, Schizophrenia, Parkinson’s disease etc.). This also includes drug/alcohol dependency related disorders;
People whose primary language is other than English;
Laboratory or clinical signs of untreated, clinically significant abnormal thyroid function;
Treatment with testosterone replacement therapy during the last five years;
Known history of prostate cancer, abnormal prostate evidenced by prostate examination, elevated levels of prostate specific antigen (PSA) (>4ng/mL) for participants age 50 years old and over;
Uncontrolled hypertension, diabetes mellitus, renal disease (eGFR <50 mL/min), cardiac disease, haematological disease, liver or lung disease;
Systolic Blood Pressure >170mmHg and Diastolic Blood Pressure >100mmHg

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)
Informed consent will be obtained prior to initiation of any clinical screening procedure. Informed consent may be obtained up to 28 days before the first treatment. More than one visit may be required to complete all the screening evaluations.

If the participant meets all the inclusion and none of the exclusion criteria, randomisation will be performed via the IVRS/IWRS. Randomisation number and treatment kit numbers will be provided by IVRS/IWRS. Participants, medical doctors, and the research staff will be blinded to the randomisation outcome. Administration of study drug or placebo will commence within 28 days of screen.

Participants will subsequently be administered either testosterone or placebo injection.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Assignment will be randomised using Interactive Voice Response System (IVRS)/Interactive Web Response System (IWRS). We will provide the age, admission GCS score, and education.
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
The design is a proof-of-concept, double-blind, randomised, placebo-controlled clinical trial.
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
Statistical analyses will include estimates of effect (% success) together with 95% confidence intervals. Exploratory analyses will include ANOVA, chi-squared, t-tests, and regression techniques where appropriate. It is planned to make formal comparisons between the randomized groups to assess the efficacy of testosterone injection compared to placebo.
The requisite number of participants was determined by a priori analysis using G*Power version 3.1.5. Based on two-tailed analysis with a medium effect size of .30 and an alpha of .05., a sample size of 80 (df=78) would be needed to achieve a power of .79.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/02/2014
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
80
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 287217 0
Government body
Name [1] 287217 0
Neurotrauma Research Program (NRP) Project Grant
Country [1] 287217 0
Australia
Funding source category [2] 287218 0
Charities/Societies/Foundations
Name [2] 287218 0
The McCusker Alzheimer's Research Foundation
Country [2] 287218 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
The McCusker Alzheimer's Research Foundation
Address
Suite 22 Hollywood Medical Centre
85 Monash Ave
Nedlands WA 6008
Country
Australia
Secondary sponsor category [1] 285972 0
None
Name [1] 285972 0
None
Address [1] 285972 0
Country [1] 285972 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289996 0
Hollywood Private Hospital Research Ethics Committee
Ethics committee address [1] 289996 0
Monash Avenue
NEDLANDS WA 6009
Ethics committee country [1] 289996 0
Australia
Date submitted for ethics approval [1] 289996 0
Approval date [1] 289996 0
23/09/2013
Ethics approval number [1] 289996 0
HPH369

Summary
Brief summary
This project aims to investigate whether testosterone injections with initial administration within three months of traumatic brain injury (TBI) can assist in recovery from brain injury and reduce the risk for the development of Alzheimer’s Disease (AD) related biomarkers.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 39750 0
Prof Ralph N Martins AO
Address 39750 0
Hollywood Medical and Specialists Centre
Monash Avenue
Nedlands WA 6009
Country 39750 0
Australia
Phone 39750 0
+61 8 9347 4200
Fax 39750 0
+61 8 9347 4299
Email 39750 0
[email protected]
Contact person for public queries
Name 39751 0
Hamid R Sohrabi
Address 39751 0
Hollywood Medical and Specialists Centre
Monash Avenue
Nedlands WA 6009
Country 39751 0
Australia
Phone 39751 0
+61 8 6304 3969
Fax 39751 0
+61 8 6389 2033
Email 39751 0
[email protected]
Contact person for scientific queries
Name 39752 0
Neville Knuckey
Address 39752 0
Centre for Neuromuscular and Neurological Disorders (CNND)
The University of Western Australia (M518)
35 Stirling Highway
CRAWLEY WA 6009
Australia
Country 39752 0
Australia
Phone 39752 0
+61 8 9346 7206
Fax 39752 0
+61 8 9346 3487
Email 39752 0
[email protected]

No information has been provided regarding IPD availability


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No Supporting Document Provided



Results publications and other study-related documents

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