Nutritional Treatment for the Amelioration of Traumatic Brain Injury

Study Overview
=================
Brief Summary
-----------------
To test the feasibility of administering a commercially available neurotrophic oral nutritional supplement (ONS) for adult patients with acute traumatic brain injury at the Royal London Hospital.

Detailed Description
-----------------
The study will be a randomised controlled non-blinded trial of adult patients with acute traumatic brain injury at the Royal London Hospital. There will be randomisation to one of two non-blinded trial groups: Usual standard NHS care (control group) Usual standard NHS care plus daily oral dose of Souvenaid® ONS The trial protocol will commence between 3-7 days after admission. The trial timeline provides a summary of intervention and assessments. The trial will last 12 months. The first 6 months will be the formal trial with two groups and follow up assessments. This will be performed on intention to treat basis. After this initial phase the investigators will provide an opportunity for all participants from either group (control or treatment) to take Souvenaid® ONS for a further 6 months with a clinical follow up appointment.

Official Title
-----------------
Nutritional Treatment for the Amelioration of Traumatic Brain Injury

Conditions
-----------------
Traumatic Brain Injury

Intervention / Treatment
-----------------
* Dietary Supplement: Souvenaid oral nutritional supplement (Nutricia)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult between 18 yrs and 80 yrs of age Acute traumatic brain injury with confirmed radiological features Exclusion Criteria: Allergies to fish oil/milk/soya Medical history of galactosaemia Non-traumatic aetiology to head injury Unable to receive enteral nutrition Craniectomy during admission (loss of integrity of skull convexity) Concurrent active neurological disease Pregnancy or breastfeeding

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>Routine NHS care following traumatic brain injury | |
| Experimental: Treatment<br>Routine NHS care following traumatic brain injury plus daily dose of test compound (oral nutritional supplement) | Dietary Supplement: Souvenaid oral nutritional supplement (Nutricia)<br>* Daily dose of a commercially available oral nutritional supplement based around the active compound recipe Fortasyn Connect, produced by Nutricia, Danone.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility to conduct the protocol as stated | To assess logistical issues which might prevent a fully powered study being carried out using this protocol. The investigators will primarily be looking at retention rate. If there is an attrition rate of over 80% then this protocol will be deemed not feasible. | 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain network connectivity | As measured by resting state EEG | 10 months | 
| Cognitive function | Changes to cognitive function as measure by CANTAB-TBI cognitive test. This is a validated and widely used clinical tool for cognitive assessment in TBI and assesses cognition using the following battery of tests (range of scores in brackets with lower score being worse performance and higher being better performance): paired associates learning (0-70); reaction time (100-5100); spatial working memory (0-153); multitasking test (0-160); one touch stockings of Cambridge (0-15). | 10 months | 
| Plasma phospholipid levels | Plasma phospholipid levels will be measured using thin layer chromatography and/or LC-MS. Batch analysis | 10 months | 
| Omega-3 index | The omega-3 index will be analysed in red blood cells. Therefore, lipids will be extracted from red blood cells, followed by transesterification and quantification using gas chromatography coupled to a flame ionisation detector. | 10 months | 
| Neurofilament light levels | Plasma or serum neurofilament light levels will be measured using either a commercially available enzyme-linked immunosorbent assay, a commercially available chemi-luminescent assay, or the commercially available SIMOA assay. Combined samples will be run on each plate to account for inter plate variability. | 10 months | 
| Inflammatory markers | Inflammatory markers such as cytokines will be analysed using either enzyme-linked immunosorbent assays or a multiplex system. Combined samples will be run on each plate to account for inter plate variability. | 10 months | 
| C-reactive protein | CRP will be measured independently using an enzyme-linked immunosorbent assay. Combined samples will be run on each plate to account for inter plate variability | 10 months |