Micronutrient Supplement Effects on Cognitive Outcomes in Post-Acute TBI

Study Overview
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Brief Summary
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Traumatic brain injury (TBI) refers to neuronal damage occurring as the result of an external force being applied to brain tissue. In the United Kingdom annual figures (2013-2014) show 449,000 hospital admittances with a diagnosis of head injury with males up to five times more likely to sustain a head injury than females. Traumatic brain injury (TBI) causes life-long disability, with no significant reduction in life expectancy, affecting a diverse range of cognitive and social functions including memory, task planning and execution, impulse control, social interactions, personality changes and depression. Following traumatic brain injury acquired deficits can lead to problems with resumption of aspects of daily life, particularly in terms of returning to work and interpersonal relationships. The initial injury triggers a secondary cascade of metabolic, neurochemical and cellular changes within the brain, primarily aimed at limiting damage and stimulating repair. Paradoxically prolonged secondary cascade mechanisms, including haemorrhage, oedema, neuroinflammation and axonal injury, results in exacerbation of deficits observed. The heterogeneous on-going nature of the secondary cascade presents clinicians with opportunities to intervene in an attempt to limit neuronal damage. A large body of nutritional research has been focused on addressing the hypermetabolic and catabolic states created by secondary cascade processes in the acute stage. Addressing these demands has played a significant role in reducing mortality and infection rates following head injury, however there has not been the same depth of research investigating the post-acute period (once individuals are discharged from hospital).

Detailed Description
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Micronutrients (including vitamins, minerals and certain polyunsaturated fatty acids) are required by the brain for normal functioning and, with few exceptions, can only be obtained through dietary sources. Research into degenerative diseases of aging have linked mitochondrial aging and DNA damage caused by micronutrient deficiency to greater incidence of cognitive decline and stroke, among other diseases, in the general population, particularly in those consuming food rich in fats and carbohydrates but poor in micronutrient content. Other research focusing on cognition, behaviour and mood state has associated micronutrient deficiencies with a wide range of neurological conditions including Alzheimer's Disease, Parkinson's Disease, multiple sclerosis, autism spectrum disorders, depression, fatigue and schizophrenia. There have however been very few studies using micronutrient interventions in post-acute human TBI. In a study with thirty retired American Football players an intervention including supplementation with a broad-spectrum multivitamin, omega-3 fish oils and a number of other substances resulted in significant percentile score improvements in almost half of the participants (n=100) across a broad range of cognitive measures. Findings demonstrated that micronutrient intervention can result in significant measurable improvements in those with TBI many years following the initial insult. A normative study will be conducted with three groups assigned to Vit D, Vit C and multivitamin arms (N = 60) tested at baseline on cognitive function and post-intervention. The TBI study will recruit three groups of individuals with post-acute traumatic brain injuries and measure whether there is improved cognitive outcomes (measured by test-retest on a cognitive battery) associated with the supplements shown to be most effective in the pilot study.

Official Title
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Micronutrient Intervention Effects on Cognitive Outcomes in Post-Acute Traumatic Brain Injury

Conditions
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Traumatic Brain Injury

Intervention / Treatment
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* Dietary Supplement: Swisse Womens 50+ Ultivite Multivitamin
* Dietary Supplement: Holland and Barrett Triple Strength Omega-3 Fish Oil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: First and only traumatic brain injury. Complex mild to moderate injury. 3-24 months post-injury Exclusion Criteria: Unable to give informed consent. Already taking micronutrient/fatty acid supplements. Hemianopia Hemiplegia. Pregnant or breastfeeding. Diagnosed with clinically low blood pressure, diabetes, or disease of neurodegeneration.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multivitamin<br>Swisse Womens 50+ Ultivite Multivitamin. Once daily. | Dietary Supplement: Swisse Womens 50+ Ultivite Multivitamin<br>* Single tablet taken once daily<br>Dietary Supplement: Holland and Barrett Triple Strength Omega-3 Fish Oil<br>* Single capsule taken once daily<br>|
| Experimental: Omega-3 Fatty Acids<br>Holland and Barrett Triple Strength Omega-3 Fish Oils. Once Daily | Dietary Supplement: Swisse Womens 50+ Ultivite Multivitamin<br>* Single tablet taken once daily<br>Dietary Supplement: Holland and Barrett Triple Strength Omega-3 Fish Oil<br>* Single capsule taken once daily<br>|
| No Intervention: Control<br>Treatment as usual (cognitive rehabilitation, occupational therapy, physiotherapy; as required) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Performance on cognitive test measures (a battery of standardized tests; memory, executive function, social cognition, general intelligence, learning and processing speed) | Analysis of change in cognitive test battery results between each time point (T2 minus T1. T3 minus T2. T3 minus T1) | Three time points: baseline (T1), 8 weeks (T2) and 22 weeks (T3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average dietary intake of micronutrients and fatty acids | Analysis of dietary intake via Nutritics software (https://www.nutritics.com/p/references), average intake value for each micronutrient supplied by software output. This will be compared to recommended daily amounts to evaluate levels of sufficiency/insufficiency in each participant. | Data collected at four time points (3 day diaries) during participant's involvement in the study via participants filling in paper food diary | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TBI