Ketogenic Diet Following Moderate to Severe Pediatric Traumatic Brain Injury

Study Overview
=================
Brief Summary
-----------------
The primary objective of this study is to evaluate the feasibility and safety of using the ketogenic diet (KD) in children who sustained moderate to severe traumatic brain injury (TBI). The secondary objective is a preliminary evaluation of the outcomes of children who have had the standard of care plus the KD, compared to those with standard of care alone. Outcome measures for the secondary objective will include: need for ventriculoperitoneal shunt, duration of unconsciousness, need for any type of craniotomy, duration of post-traumatic amnesia, acute hospitalization length of stay, and cognitive and motor function at 12 months after injury. If this study demonstrates feasibility and safety, the information related to outcomes will be used to inform the planning of a future, larger, randomized study of the efficacy of the KD in children and adolescents with TBI. Specifically, this information will be used to assist with sample size calculations for this future study.

Detailed Description
-----------------
The KD is an alternative feeding regimen that has been in use since 1921. It is a high fat, low carbohydrate and moderate protein diet. There are various forms of the KD. The classic KD consists of long-chain triglycerides with a fat-to-combined-protein-and-carbohydrate ratio that can vary. At our institution, it is standard of care to initiate a ketogenic diet at a ratio of 2:1, and to increase the ratio to 3:1 or 4:1 as needed to achieve ketosis. Clinically, the KD has been proven to be an effective therapy in children and adolescents with refractory epilepsy, as well as for those with type II diabetes. In addition, an international consensus was published in 2009 that recommended the use of the KD to treat epilepsy refractory as an alternative to at least two antiepileptic medications. Before initiating the KD for epilepsy management, labs such as urine and blood ketones, blood glucose and a basic metabolic panel including magnesium are commonly recommended. Risks for long-term use of the KD include but are not limited to the following: hypercholesterolemia, mineral deficiencies, acidosis, constipation, weight loss and nephrolithiasis. However, short-term use should significantly limit the occurrence of these potential complications.

Official Title
-----------------
Ketogenic Diet Following Moderate to Severe Pediatric Traumatic Brain Injury: A Pilot Study

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

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age limits met at the time of injury and admission Participants with moderate to severe traumatic brain injury defined as a Glasgow Coma Scale Score of 3-12 (lowest score in the first 24 hours after injury). Individuals requiring craniotomy and/or evacuation of intracranial hemorrhage may be included. Exclusion Criteria: Currently on an oral diet at time of screening or currently on IV-only and in opinion of Pediatric Intensive Care Unit intensivist will be transitioning to an oral diet, not tube-feeding Anoxia/ischemia as a significant portion of injury, including near-drowning Non-accidental traumatic brain injury (i.e., assault, abuse) Penetrating injury including gunshot wounds Pregnancy Any condition that in the opinion of the Pediatric Intensive Care Unit or neurosurgery medical staff warrants exclusion from the study

Ages Eligible for Study
-----------------
Minimum Age: 2 Years
Maximum Age: 17 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prospective Intervention Group<br>Participants will receive standard of care for acute management of moderate to severe traumatic brain injury, together with a weight-based ketogenic diet added for up to fourteen days. | Other: Ketogenic Diet<br>* The ketogenic diet (KD) is an alternative feeding regimen that has been in use since 1921. It is a high-fat, low carbohydrate, and moderate protein diet. There are various forms of the KD. The classic KD consists of long-chain triglycerides with a fat-to-combined-protein-and-carbohydrate ratio that can vary. At the investigating institution, it is standard of care to initiate a ketogenic diet at a ratio of 2:1, and to increase the ratio to 3:1 or 4:1 as needed to achieve ketosis.<br>* Other names: Keto;|
| No Intervention: Historical Control Group<br>Medical records of past TBI patients will be used as controls matched for age, gender, socioeconomic status (type of health care coverage including private insurance vs. government-funded coverage), lowest first 24 hour post-injury Glasgow Coma Score (GCS) (<8 or 8-12), and pre-injury school program (regular or special education). | |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ability to complete a course of the ketogenic diet (KD) | Safety and feasibility will be determined by the ability to complete a 14-day course of the KD after TBI without needing to terminate the diet due to intolerance resulting from gastrointestinal side effects (for example, nausea and vomiting, diarrhea, or acidosis), or due to abnormal findings on laboratory tests. Outcome is reported as the number of participants who complete the 14-day keto diet treatment. | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Unconsciousness | Outcome is reported as the length of time (in hours) a participant is unconscious following their injury. | 14 days | 
| Need for Surgeries | Outcome is reported as the number of surgeries required in each group following injury. | 14 days | 
| Duration of Acute Hospitalization | Outcome is reported as the length (in days) of acute hospitalization following injury. | 14 days | 
| Duration of Post-traumatic Amnesia | Outcome is reported as the length of time (in days) that a participant experiences amnesia following their injury. | 14 days |