Ketogenic Diet for Traumatic Brain Injury (KETI)

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

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.

Study Overview

• Status: Completed
• Conditions: Traumatic Brain Injury; Ketogenic Dieting
• Intervention / Treatment: Other: 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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Severe Traumatic Brain Injury
2. GCS<= 8 with severe head injury
3. Age more than 18years

Exclusion Criteria:

1. Diabetic Ketoacidosis
2. Unstable metabolic condition (persistent hyponatremia, hypernatremia, hypoglycemia, hypocalcemia, acidosis)
3. Cardiorespiratory or hemodynamic instability
4. Coagulopathy
5. Pancreatitis
6. Liver Failure
7. Severe hyperlipidemia
8. Inability to tolerate enteral feeds including ileus
9. Known Fatty acid oxidation disorder or pyruvate carboxylase deficiency
10. Any terminally ill patient with poor brain stem reflexes and mortality within 24h of admission.
11. Pregnant Females

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Subjects on Ketogenic diet; 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; 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.; 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)

Collaborators and Investigators

• Sponsor: University of Missouri-Columbia

Publications and helpful links

General Publications

• Arora N, Litofsky NS, Golzy M, Aneja R, Staudenmyer D, Qualls K, Patil S. Phase I single center trial of ketogenic diet for adults with traumatic brain injury. Clin Nutr ESPEN. 2022 Feb;47:339-345. doi: 10.1016/j.clnesp.2021.11.015. Epub 2021 Nov 16.

Study record dates

Study Major Dates

• Study Start (Actual): July 4, 2019
• Primary Completion (Actual): April 30, 2024
• Study Completion (Actual): April 30, 2024

Study Registration Dates

• First Submitted: June 3, 2019
• First Submitted That Met QC Criteria: June 7, 2019
• First Posted (Actual): June 11, 2019

Study Record Updates

• Last Update Posted (Actual): May 3, 2024
• Last Update Submitted That Met QC Criteria: May 2, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic
• Other Study ID Numbers: 2014675

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Not yet decided which IPD to share

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No