Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613000711718
Ethics application status
Approved
Date submitted
18/06/2013
Date registered
28/06/2013
Date last updated
29/08/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Brain Injury and NeuroAid Supplementation
Scientific title
For a patient who has experienced mild or moderate brain injury, will NeuroAid II as compared to placebo improve functioning?
Secondary ID [1] 282692 0
Nil
Universal Trial Number (UTN)
U1111-1144-6921
Trial acronym
BRAINS (BRAin Injury and NeuroAid Supplementation)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mild and moderate traumatic brain injury 289405 0
Condition category
Condition code
Injuries and Accidents 289729 289729 0 0
Other injuries and accidents
Alternative and Complementary Medicine 289730 289730 0 0
Herbal remedies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
NeuroAid II (MLC901) which contains 9 herbal components (Radix astragali, Radix salvia miltiorrhizae, Radix paeoniae rubra, Rhizoma chuanxiong, Radix angelicae sinesis, Carthamus tinctorius, Prunus persica, Radix polygalae and Rhizoma acori tatarinowii). The dose is standard at 2 capsules (0.4g/capsule) 3x/day by oral administration for 6 months.
Adherence will be measured through counting the number of capsules not taken by the participant at each follow-up assessment
Intervention code [1] 287352 0
Treatment: Other
Comparator / control treatment
Placebo 2 capsules taken 3x/day for 6 months. Each placebo capsule contains Dextrin (331.7mg), Caramel (66.3mg) and Magnesium stearate (2mg) by oral administration.
Control group
Placebo

Outcomes
Primary outcome [1] 289819 0
CNS-Vital Signs computerised neuropsychological assessment, Neurocognition Index
Timepoint [1] 289819 0
Primary timepoint[1] is 6 month follow-up
Secondary outcome [1] 303307 0
Everyday memory difficulties (Cognitive Failures Questionnaire)
Timepoint [1] 303307 0
3, 6 and 9 month follow-up
Secondary outcome [2] 303308 0
post-concussion symptoms (Rivermead Post Concussion Symptoms Questionnaire)
Timepoint [2] 303308 0
3, 6 and 9 month follow-up
Secondary outcome [3] 303309 0
health related quality of life (QOLIBRI)
Timepoint [3] 303309 0
3, 6 and 9 month follow-up
Secondary outcome [4] 303310 0
Mood (Hospital Anxiety and Depression Scale)
Timepoint [4] 303310 0
3, 6 and 9 month follow up
Secondary outcome [5] 303311 0
Fatigue (Fatigue Impact Scale)
Timepoint [5] 303311 0
3, 6 and 9 month follow-up
Secondary outcome [6] 303312 0
Adverse events (nature and duration event experienced) e.g., abdominal discomfort. This outcome will be assessed by a weekly phone call for 2 weeks following initial administration. Any adverse events reported will be recorded for its nature, duration in days and any action taken.
Timepoint [6] 303312 0
3, 6 and 9 month follow-up

Eligibility
Key inclusion criteria
Aged 18-65 years
1-12 months post-TBI
Ability to provide informed consent
Experiencing cognitive impairment following injury
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Pre-Brain injury disability
Severe brain injury
Co-existing severe comorbidity
Current participation in another clinical trial
Pregnancy (suspected or confirmed)
Breast- feeding
Not fluent in English or have aphasia
Unknown date of injury
Known allergy to NeuroAid or its component ingredients

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)
This pilot study will include 140 patients who experienced a mild or moderate TBI in the Auckland and Hamilton regions. Eligible participants will be randomized to receiving either NeuroAid II (MLC901) or placebo using a computer randomisation programme. This will be a community-based study recruiting consecutive acute TBI patients through the Auckland City Hospital (Auckland) and Waikato Hospital (Hamilton) trauma units, Accident & Medical Clinics, TBI service providers and self-referrals. Assessors and participants will be blind to treatment allocation. Allocation to group will be determined by a central computerised randomisation programme
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
After consenting to participate in the study and completing the baseline assessment, eligible participants will be randomised to receive either the NeuroAid supplement or placebo using 1:1 minimisation randomisation. This approach stratify by center [Hamilton/Auckland], time since injury [1-2 months/2-3months] and sex. The study will be un-blinded only after group analyses have been completed. A researcher will randomise eligible participants using the computerised Minim randomisation programme at the National Institute for Stroke and Applied Neurosciences, AUT University.
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 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Descriptive analyses: data collected at baseline will be reported and compared between the NeuroAid and Control (placebo) groups. These baseline differences and differences in outcome will be tabulated between the Neuroaid and the Control group at 1, 3, 6 and 9 month follow-up. All analyses will be conducted by intention to treat. These will be summarised using means (95% confidence intervals [CI]), standard deviations, quartiles and range. Protocol analyses will be carried out for necessary variables from each follow-up.

Confirmatory analyses
Inferential analyses

Efficacy analyses – to identify any positive effect of NeuroAid on individuals with TBI using the primary and secondary outcomes.

Primary analyses – the primary outcome CNS- Vital Signs neurocognition index.

Secondary analyses – total scores and sub-scale scores of cognitive ability, post-concussion symptoms, mood, fatigue, quality of life and frequency of adverse events. Rates of adverse events will be determined to enable comparison between the proportion of patients with at least one adverse event in the NeuroAid group in comparison to the placebo group.

All data analysis will be carried out with adjustments made to account for multiple comparisons using a normality-based approach. Repeated measures analyses will be analysed using mixed linear regression models adjusting for baseline and potential covariates including but not limited to age, gender, severity of injury. The participant will be used to represent the random effect. Model selection will be undertaken with each outcome using standard selection heuristics. Covariates will be selected based on improving the overall efficiency of the model. Regardless, baseline and age, gender, severity of injury will be included in the model. Selecting covariates for inclusion in these models may be done by:
- Pooling the SD observed for the outcome in each arm (NeuroAid and placebo) to create an F-value. If the mean difference for an outcome between each arm exceeds this F-value then it should be included as a covariate in the model.
- If a significant difference is observed for an outcome between the two arms of the trial

Potential confounders, due to an imbalance between the two trial arms will also need to be adjusted for.

In the event that blatant non-normality is observed (from assessment of residuals) or an association with any other predictor is observed then alternate analyses such as GEE (generalised estimating equation) and exponential family distributions will be considered.

Covariates such as age, gender and severity of injury will also be examined in relation to the pattern of response of treatment

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Interim analysis identified no safety concerns and a positive treatment effect
Date of first participant enrolment
Anticipated
1/10/2013
Actual
1/07/2014
Date of last participant enrolment
Anticipated
28/02/2015
Actual
19/07/2016
Date of last data collection
Anticipated
Actual
18/04/2017
Sample size
Target
140
Accrual to date
Final
79
Recruitment outside Australia
Country [1] 5148 0
New Zealand
State/province [1] 5148 0
Auckland and Hamilton

Funding & Sponsors
Funding source category [1] 287462 0
Commercial sector/Industry
Name [1] 287462 0
Moleac Ltd
Country [1] 287462 0
Singapore
Primary sponsor type
University
Name
AUT University
Address
AUT City Campus
Wellesley Street
Auckland
New Zealand
1142
Country
New Zealand
Secondary sponsor category [1] 286206 0
None
Name [1] 286206 0
Address [1] 286206 0
Country [1] 286206 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289438 0
New Zealand Health and Disability Ethics Comittee
Ethics committee address [1] 289438 0
Ministry of Health
No 1 The Terrace
PO Box 5013
Wellington
6145
Ethics committee country [1] 289438 0
New Zealand
Date submitted for ethics approval [1] 289438 0
15/07/2013
Approval date [1] 289438 0
09/05/2014
Ethics approval number [1] 289438 0

Summary
Brief summary
Many people who have had a traumatic brain injury experience cognitive and functional difficulties that can have a significant impact on their ability to return to everyday life (such as returning to employment and maintaining social relationship). NeuroAid is a herbal supplement that has been shown to improve neurological deficits in people who have experienced a stroke. This pilot clinical trial will examine if NeuroAid shows trends in cognitive and functional improvement in 140 people who have experienced a mild or moderate traumatic brain injury in the last 1 to 3 months as compared to a placebo control group (inactive capsule). Participants will be given either NeuroAid II or placebo to take 3x daily for 6 months. Participants will be asked to complete a computerised cognitive test and questionnaires about their symptoms, mood and quality of life. These assessments will be carried out before, during and after participants have taken their treatment so that we can compare the results between the two groups.
Trial website
www.nisan.aut.ac.nz
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 40854 0
Prof Valery Feigin
Address 40854 0
AA254A, AUT North Shore Campus
90 Akoranga Drive
Northcote
Auckland
NZ
1142
Country 40854 0
New Zealand
Phone 40854 0
+64 9 921 9166
Fax 40854 0
+64 9 921 9620
Email 40854 0
[email protected]
Contact person for public queries
Name 40855 0
Dr Alice Theadom
Address 40855 0
AA254C, AUT North Shore Campus
90 Akoranga Drive
Northcote
Auckland
NZ
1142
Country 40855 0
New Zealand
Phone 40855 0
+64 9 921 9999 x 7805
Fax 40855 0
+64 9 921 9620
Email 40855 0
[email protected]
Contact person for scientific queries
Name 40856 0
Dr Alice Theadom
Address 40856 0
AA254C, AUT North Shore Campus
90 Akoranga Drive
Northcote
Auckland
NZ
1142
Country 40856 0
New Zealand
Phone 40856 0
+64 9 921 9999 x 7805
Fax 40856 0
+64 9 921 9620
Email 40856 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
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