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Trial registered on ANZCTR


Registration number
ACTRN12619001216101p
Ethics application status
Submitted, not yet approved
Date submitted
30/05/2019
Date registered
2/09/2019
Date last updated
2/09/2019
Date data sharing statement initially provided
2/09/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Micronutrients and traumatic brain injury: a feasibility study
Scientific title
Micronutrients and traumatic brain injury: a feasibility study
Secondary ID [1] 298255 0
NIL
Universal Trial Number (UTN)
U1111-1230-3860
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Emotion dysregulation 312858 0
Traumatic Brain Injury 313135 0
Condition category
Condition code
Mental Health 311355 311355 0 0
Anxiety
Mental Health 311356 311356 0 0
Depression
Mental Health 311357 311357 0 0
Other mental health disorders
Neurological 311611 311611 0 0
Other neurological disorders
Injuries and Accidents 311613 311613 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All participants will be receiving a micronutrient formula for 6 months. The micronutrient formula will be made available in capsule and powder form. Whether the participants take the formula in a capsule or powder form, or a combination of both, will depend on both their preference and whether or not they are able to swallow the capsules. Participants will be asked to ingest 9 capsules daily, three capsules, three times a day or the equivalent in powder form. It is recommended the micronutrients are taken with food. The micronutrient intervention is a blend of vitamins, minerals, antioxidants and amino acids. The formula, Daily Essential Nutrients, is being manufactured and donated by Hardy Nutritionals (Registered Trademark), Canada and consists of the following ingredients. The following doses are for 12 capsules (full dose per day): Vitamin A (as retinyl palmitate), 5,760 IU; Vitamin C (as ascorbic acid), 600 mg; Vitamin D (as cholecalciferol), 3,000 IU; Vitamin E (as d-alpha tocopheryl succinate), 360 IU; Vitamin K (75% as phylloquinone; 25% as menaquinone-7), 120 mcg; Thiamin (as thiamin mononitrate), 60 mg; Riboflavin, 18 mg; Niacin (as niacinamide), 90 mg; Vitamin B6 (as pyridoxine hydrochloride), 69.9 mg; Folate (as L-methylfolate calcium), 801 mcg; Vitamin B12 (as methylcobalamin), 900 mcg; Biotin, 1080 mcg; Pantothenic acid (as d-calcium pantothenate), 30 mg; Calcium (as chelate), 1,320 mg; Iron (as chelate), 13.8 mg; Phosphorus (as chelate), 840 mg; Iodine (as chelate), 204 mcg; Magnesium (as chelate), 600 mg; Zinc (as chelate), 48 mg; Selenium (as chelate), 204 mcg; Copper (as chelate), 7.2 mg; Manganese (as chelate), 9.6 mg; Chromium (as chelate), 624 mcg; Molybdenum (as chelate), 144 mcg; Potassium (as chelate), 240 mg. Proprietary blend: Choline bitartrate, Alpha-lipoic acid, Mineral wax, Inositol, Acetyl-L-carnitine, Grape seed extract, Ginkgo biloba leaf extract, L-methionine, N-acetyl-L-cysteine, Boron, Vanadium, Lithium orotate, Nickel. Other ingredients: Vegetarian capsule (hypromellose), microcrystalline cellulose, magnesium stearate, silicon dioxide, titanium dioxide.
Adherence to the intervention will be assessed monthly through pill taking records kept by the participants.
Intervention code [1] 314516 0
Treatment: Other
Comparator / control treatment
There is no control group in this study. All participants will be observed and assessed monthly to determine whether there are changes to pre- intervention symptoms and post- intervention outcomes.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 320108 0
Affective Reactivity Index (ARI) will be used to measure feelings, behaviours and impairment specific to irritability.
Timepoint [1] 320108 0
Baseline (week 0), baseline (week 2), once a month for the 6 months of the intervention, 6- months post intervention
Secondary outcome [1] 370547 0
ADHD Rating Scale IV – (ADHD –RS) –
Timepoint [1] 370547 0
Baseline (week 0), baseline (week 2), once a month for the 6 months of the intervention, 6- months post intervention
Secondary outcome [2] 370548 0
Overt Behaviour Scale- Kids, Modified (the rape scale will be taken out)
Timepoint [2] 370548 0
Baseline (week 0), end of intervention (Month 6), follow up 6 months post intervention
Secondary outcome [3] 370549 0
Behaviour Rating Inventory of Executive Function (BRIEF, parent form),is a behavioural rating measure that was specifically designed to assess child and adolescent everyday executive skills in natural, everyday environments, including home and school. The BRIEF is composed of two major index scales and a composite of the two, which are the Behavioral Regulation Index (BRI), the Metacognition Index (MI), and the Global Executive Composite (GEC). Each of the two major index scales is further composed of scales. There are Eight clinical scales (Inhibit, Shift, Emotional Control, Initiate, Working Memory, Plan/Organize, Organization of Materials, Monitor) and two validity scales (Inconsistency and Negativity). The BRI is composed of the Inhibit, Shift, and Emotional Control scales, and the MI is composed of the Initiate, Working Memory, Plan/Organize, Organization of Materials, and Monitor scales. It takes 15 minutes to administer. It is completed by parents.
Timepoint [3] 370549 0
Baseline (week 0), at the end of the intervention (month 6) and 6 months post intervention
Secondary outcome [4] 370550 0
The Behaviour Rating Inventory of Executive Function (BRIEF, teacher form) is the teacher version of the parent questionnaire described above.
Timepoint [4] 370550 0
Baseline (week 0), at the end of the intervention (month 6) and 6 months post intervention
Secondary outcome [5] 370551 0
Strength and Difficulty Questionnaire (SDQ, parent form) assesses positive and negative psychological attributes measuring both problem behaviours and competencies. The SDQ give a total difficulties score that ranges from 0-40. The SDQ examines 25 attributes, divided between 5 scales: Emotional Problems, Conduct Problems, Hyperactivity and Inattention, Peer Relationship Problems and Prosocial Behaviours (excluded from Total Difficulties score). A separate scale measures the nature of the person's problems as assessed by parents including burden to others, social impairment, chronicity and distress relate to a reported problem.
Timepoint [5] 370551 0
Baseline (week 0), baseline (week 2), once a month for the 6 months of the intervention, 6- months post intervention
Secondary outcome [6] 370552 0
Strength and Difficulty Questionnaire (SDQ, teacher form) is the teacher version of the parent questionnaire described above.
Timepoint [6] 370552 0
Baseline (week 0), baseline (week 2), once a month for the 6 months of the intervention, 6- months post intervention
Secondary outcome [7] 371218 0
Clinical Global Inventory (CGI) assesses the severity of illness and changes from baseline
Timepoint [7] 371218 0
Baseline (week 0), baseline (week 2), once a month for the 6 months of the intervention, 6- months post intervention
Secondary outcome [8] 371222 0
Parenting Stress Index (PSI)
Timepoint [8] 371222 0
Baseline (week 0), baseline (week 2), at the end of the intervention (month 6), 6 months post intervention
Secondary outcome [9] 371223 0
Side effect questionnaire adapted for this study and used with children, this measure asks the participant to rate any physical side effects they may have experienced in the last two weeks, which they attribute to taking the capsules.
Participant self-report of physical symptoms which may be attributed to the micronutrient intervention.
Adverse events will be monitored closely to ensure participants' safety. The most common adverse effects have been found to be of a gastrointestinal nature. These adverse effects can be avoided by titrating the treatment and taking the capsules with food and water or the powder combined with smoothies.
Timepoint [9] 371223 0
Baseline (week 0), baseline (week 2), once a month for the 6 months of the intervention, 6- months post intervention

Eligibility
Key inclusion criteria
1) Between 6 and 13 years, 2) must be children or young people with a Traumatic Brain Injury more than a year old, and 3) meet the criteria for emotional dysregulation as defined by the Affective Reactivity Scale. Participants will be assessed on the ARI- P (parent scale). Those scoring more than 3 will be considered eligible.
Minimum age
6 Years
Maximum age
13 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) A known allergy to any of the ingredient used in the intervention, 2) any known abnormality of mineral metabolism (e.g., Wilson's disease, haemochromatosis – assessed via blood tests), 3) ingestion of any medications with primarily central nervous system activity, including mood stabilizers, atomoxetine or stimulants. Participants must have been off their medications for a minimum of four weeks prior to the trial. Participants will not be encouraged to come off their medications in order to participate.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Not applicable
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Feasibility study using individual case studies where all participants are given access to the treatment
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Based on the definitions proposed above, this study's endpoint has been selected as Safety/ efficacy.
All statistical analyses will be carried out using the Statistical Package for Social Science (SPSS), Excel and sigma plot. This study’s data analysis will be predominantly a descriptive time series of the various Dependent Variables measured such as emotional dysregulation and ADHD.
The researchers will undertake two baseline measures two weeks apart to establish stability in the various core dependent variables and observe any regression to the mean effects.

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 outside Australia
Country [1] 21493 0
New Zealand
State/province [1] 21493 0
Christchurch

Funding & Sponsors
Funding source category [1] 302797 0
University
Name [1] 302797 0
University of Canterbury Department of Psychology Research Funds
Address [1] 302797 0
Department of Psychology
University of Canterbury
Private Bag 4800
Christchurch 8140
Country [1] 302797 0
New Zealand
Primary sponsor type
Charities/Societies/Foundations
Name
University of Canterbury Foundation- donations given to the principal investigator
Address
University of Canterbury
Private Bag 4800,
Christchurch 8140
Country
New Zealand
Secondary sponsor category [1] 302745 0
Commercial sector/Industry
Name [1] 302745 0
Hardy Nutritionals (Registered Trademark)
Address [1] 302745 0
69B Broadway Street North
PO Box 919
Raymond, Alberta
Canada T0K 2S0

Country [1] 302745 0
Canada

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 303386 0
Health and Disability Ethics Committees
Ethics committee address [1] 303386 0
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 303386 0
New Zealand
Date submitted for ethics approval [1] 303386 0
16/07/2019
Approval date [1] 303386 0
Ethics approval number [1] 303386 0

Summary
Brief summary
Traumatic Brain Injury (TBI) is the leading cause of death and long- term disability in children and young adults worldwide. Currently, the incidence rate is estimated between 150 to 300 per 100,000 population per year. In New Zealand, the total incidence rate is 790 per 100,000 people per year and children and adolescents account for 70% of this number. Research shows that those numbers may be underestimated since only people who have sought treatment are likely to be included. Outcomes depend on many pre-TBI factors but most research found that personality changes and behavioural problems were common post injury TBI outcomes. The proposed research is a feasibility study investigating whether children with a Traumatic Brain Injury are able to adhere to a six months intervention of broad-spectrum micronutrient formula, to assess the safety and tolerability of a specific formulation, Daily Essential Nutrients, on this population and to observe if there are any changes in the children’s ability to manage their emotions. The study also aims to understand whether individual comorbid symptoms, determined during an initial interview with participants and families, vary during the intervention. Based on previous research, we expect those symptoms to be low mood, anxiety, sleep disturbances and ADHD.
Trial website
Trial related presentations / publications
Public notes
Hardy Nutritionals (Registered Trademark) are the manufacturer of the study intervention and have no other involvement in the study other than donating the product free of charge.
ACC case managers will help in identifying suitable candidates, providing them with information and getting them to contact the research team directly. ACC case managers will have no further involvement in the study.

Contacts
Principal investigator
Name 93494 0
Prof Jullia Rucklidge
Address 93494 0
Mental Health and Nutrition Research Group
Department of Psychology
University of Canterbury
Private Bag 4800,
Christchurch 8140
Country 93494 0
New Zealand
Phone 93494 0
+64 3369 4398
Fax 93494 0
+64 3364398
Email 93494 0
julia.rucklidge@canterbury.ac.nz
Contact person for public queries
Name 93495 0
Mrs Sophie Waretini
Address 93495 0
Mental Health and Nutrition Research Group
Department of Psychology
University of Canterbury
Private Bag 4800,
Christchurch 8140
Country 93495 0
New Zealand
Phone 93495 0
+64 33694398
Fax 93495 0
Email 93495 0
sophie.waretini@pg.canterbury.ac.nz
Contact person for scientific queries
Name 93496 0
Prof Julia Rucklidge
Address 93496 0
Mental Health and Nutrition Research Group
Department of Psychology
University of Canterbury
Private Bag 4800,
Christchurch 8140
Country 93496 0
New Zealand
Phone 93496 0
+64 3369 4398
Fax 93496 0
Email 93496 0
julia.rucklidge@canterbury.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
This study does not ask for participants' consent to share their data beyond this study.
What supporting documents are/will be available?
Study protocol
How or where can supporting documents be obtained?
Type [1] 2135 0
Study protocol
Citation [1] 2135 0
Link [1] 2135 0
Email [1] 2135 0
Other [1] 2135 0
Summary results
No Results