Ketogenic Diet for Traumatic Brain Injury

Study Overview
=================
Brief Summary
-----------------
Traumatic Brain Injury is a major health concern in United States. There is a un-met need to develop new therapeutic options for faster neuron recovery without causing significant side effects. The role of ketones in neuronal recovery has been studied and has been found to be useful in decreasing size of contusion. The present study aims to study the safety and feasibility profile of ketogenic diet.

Detailed Description
-----------------
Traumatic Brain Injury (TBI) is a major health concern for United States contributing nearly one-third of injury-related deaths in United States. The Centers for Disease Control and Prevention (CDC) estimates that 1.7 million people in the United States sustain a TBI each year. It is responsible for significant disabilities and the total cost of productivity loss was estimated to be $76.5 billion in the United States in 2004. Several animal models have demonstrated the effectiveness of ketones in brain injury to decrease the size of contusion, improving cortical ATP levels, reduced brain edema and cellular apoptosis. Ketones have been shown to be effective in neuromodulation in animal models. Evaluation of carbohydrate free diet has been done in traumatic brain injury patients and it was noted to not cause fluctuations in blood glucose. There is a need for safety and feasibility study of ketogenic diet in traumatic brain injury patients and to understand the effectiveness in neuromodulation in humans. The present study focuses on identifying the safety and feasibility of KD in traumatic brain injury patients. This pilot project data will be utilized to design future randomized clinical trials. Based on the safety data, further trials will be conducted to evaluate the effectiveness of KD in traumatic brain injury patients and its effectiveness in controlling elevated intracranial pressure. It will open the avenue for consideration of new treatment option for intracranial pressure management and functional recovery. From a nutrition perspective, Ketogenic diet might become the standard of care for this patient population.

Official Title
-----------------
Safety and Feasibility of Ketogenic Diet for Traumatic Brain Injury Study Protocol

Conditions
-----------------
Traumatic Brain Injury, Ketogenic Dieting

Intervention / Treatment
-----------------
* Other: Ketogenic diet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Severe Traumatic Brain Injury GCS<= 8 with severe head injury Age more than 18years Exclusion Criteria: Diabetic Ketoacidosis Unstable metabolic condition (persistent hyponatremia, hypernatremia, hypoglycemia, hypocalcemia, acidosis) Cardiorespiratory or hemodynamic instability Coagulopathy Pancreatitis Liver Failure Severe hyperlipidemia Inability to tolerate enteral feeds including ileus Known Fatty acid oxidation disorder or pyruvate carboxylase deficiency Any terminally ill patient with poor brain stem reflexes and mortality within 24h of admission. Pregnant Females

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

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

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

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

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subjects on Ketogenic diet<br>Treatment with KD will consist of 4:1 [fat]: [protein + carbohydrate] weight ratio. KD will be started as soon as the patient is ready for alimentation (while they are in neurocritical care unit). The rate of feeds will be calculated by trained dietician on service. Ketogenic diet will be continued during the entire length of ICU stay. Supplementation with vitamins, calcium and phosphorus will be done. | Other: Ketogenic diet<br>* Subjects will be provided with the Ketogenic diet in the form of tube feeds once the decision is made to start the patient on diet.<br>* Other names: Ketovie;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of Ketogenic Diet on Intracranial Pressure | Intracranial Pressure will be measured hourly and it will be trended daily. | Baseline, till patient on KD (maximim 1 month) | 
| Development of Ketosis in blood | Serum beta-hydroxybutyrate will be done alternate day to assess the level of ketosis in blood. | Baseline, till patient on KD ( maximum 1month) | 
| Excretion of Ketones in Urine | Urine Ketones will be measured alternate day to assess the level of ketosis | Baseline, till patient on KD (maximum 1 month) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate change in the neurological exam | Neurological exam will be documented with Glasgow Coma Scale. | Baseline, before discharge from ICU | 
| Evaluate subjects with gastro-intestinal adverse effects | Adverse effects like Diarrhea, vomiting, abdominal distension (ileus), abdominal tenderness will be monitored. | Baseline, till patient on KD (Maximum 1month) | 
| Evaluate subjects for muscle wasting | Urinary Nitrogen and urinary creatinine will be measured alternate day to look for muscle wasting. | Baseline, till patient on Kd (Maximum 1month) |