Ketogenic Diet & Functional Recovery in Moderate to Severe Traumatic Brain Injury

Traumatic Brain Injury (TBI) represents a significant public health risk in the United States leaving many survivors with significant long term cognitive deficits and at risk for neurodegenerative diseases. Despite extensive research there are no pharmacological therapies which have demonstrated significant improvement in neurological or cognitive recovery. Changes in glucose metabolism are considered the hallmark metabolic response to TBI and ketosis has been proposed as a therapy to ameliorate metabolic dysfunction. This trial investigates the therapeutic potential of a ketogenic or modified Atkins diet on neurocognitive outcome following moderate-severe TBI.

Study Overview

• Status: Enrolling by invitation
• Conditions: Traumatic Brain Injury
• Intervention / Treatment: Other: Standard diet; Other: ketogenic/modified Atkins diet

Detailed Description

Traumatic Brain Injury (TBI) represents a significant public health risk in the United States leaving many survivors with significant long term cognitive deficits and at risk for neurodegenerative diseases. Despite extensive research there are no pharmacological therapies which have demonstrated significant improvement in neurological or cognitive recovery. Changes in glucose metabolism are considered the hallmark metabolic response to TBI and ketosis has been proposed as a therapy to ameliorate metabolic dysfunction. Further research is necessary to address the outstanding questions regarding outcome, dose, timing, route and duration of ketogenic diet (KD) or modified Atkins diet (MAD) therapy in clinical TBI. Using a multiparametric MRI and MR spectroscopy approach in conjunction with standardized neurological and neuropsychological assessments of outcome, disability, cognition, and quality of life, this trial will investigate the therapeutic potential of KD/MAD on 12 month outcome following moderate-severe TBI patients.

The purpose of this project is to:

1. Determine the effect of KD/MAD on cognitive and neurological outcome following moderate - severe TBI. To date clinical studies of ketone metabolism in TBI are severely limited and have focused primarily on ketometabolism and its effects on glucose metabolism without assessing functional or cognitive outcomes. This project directly assesses the effect of KD/MAD on measures of disability, attention, memory, processing speed, language, and executive function during ketosis and will determine whether its effects outlast the duration of the diet.
2. Identify the effects of KD/MAD on cerebral metabolism following moderate - severe TBI. While the use of ketogenic fuels is receiving greater attention, little is known about the effect of the KD/MAD on neuronal metabolism. This project will use MR spectroscopy to non-invasively measure NAA, a marker of neuronal metabolism during ketosis and outside the treatment window, which will deepen our understanding of the neuroprotective mechanisms of this therapy.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• complicated mild (GCS 13-15), moderate (GCS 9 - 12) to severe (GCS ≤ 8) traumatic brain injury (TBI) between 2-30 days post injury
• Admitted to Loma Linda University surgical intensive care unit (SICU)

Exclusion Criteria:

• history of comorbid ischemic stroke following qualifying TBI
• history of premorbid brain injury with associated loss of consciousness
• history of psychiatric disorder
• history of premorbid neurological disorder or neurosurgical intervention
• pregnancy
• depressed GCS score due to acute intoxication
• liver dysfunction as defined by liver enzymes 5 times the upper limit of normal or chronic cirrhosis
• acute renal failure according to the Risk, Injury, Failure, Loss of kidney function, and End-stage kidenty disease (RIFLE) classification
• abdominal surgery during the same admission
• type 1 diabetes
• gastroparesis
• dyslipidemia
• severe asphasia
• known history of metabolic disorders that are a contradiction for ketogenic diet (KD) such as primary carnitine deficient, carnitine palmitoyltransferase (CPT) I or II deficiency, carnitine translocase deficiency, beta-oxidation defects, pyruvate carboxylase deficiency, or porphyria
• prealbumin (transthyretin) levels of <10 mg/dL within 3 days of admission
• Metal, implanted device (ICP monitor), pregnancy, claustrophobia, or other contraindication to MRI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: TBI SD; TBI subjects on a standard (normal) diet	Other: Standard diet; standard (normal) diet use
Experimental: TBI KD/MAD; TBI subjects on a ketogenic/modified Atkins diet	Other: ketogenic/modified Atkins diet; ketogenic/modified Atkins diet use

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurological outcome	The Disability Rating Scale (DRS) will be used to measure general functional changes as a result of the dietary intervention over a 6 month recovery period. This scale ranges from 0 (without disability) to a maximum score of 29 (extreme vegetative state).	day 0 to 12 months
Change in cerebral metabolism	Single voxel magnetic resonance spectroscopy will be used to assess changes in cerebral metabolism as a result of the dietary intervention.	day 0 to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurocognitive outcome: Trail Making Test, Part B	A change in visual motor and visual spatial ability and mental flexibility as a result of the dietary intervention will be assessed over a 6 month period. Results are reported as the number of seconds required to complete the task with higher scores reveal greater impairment.	day 0 to 12 months
Neurocognitive outcome: Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)	A change in cognitive improvement as a result of the dietary intervention will be assessed across 5 domains using the RBANS: Immediate Memory - List learning and Story Memory Visuospacial/Constructional - Figure Copy and Line Orientation Language - Picture naming and Semantic Fluency Attention - Digit Span and Coding Delayed Memory - List Recall, List Recognition, Story Memory, and Figure Recall The five domain scores are combined as a total scale score. According to the RBANS manual, the possible values for the RBANS scores at the item, domain, and scale level are 0 to 89, 40 to 154, and 40 to 160.	day 0 to 12 months
Neurocognitive outcome: Delis Kaplan Executive Function System (D-KEFS)	A change in executive function as a result of the dietary intervention will be assessed over a 6 month period using the verbal fluency and color word interference subtests of the D-KEFS. Achievement scores (total correct responses and total switching accuracy) will be measured using the D-KEFS Scoring Assistant software.	day 0 to 12 months
Neurocognitive outcome: 36 Item Short Form Survey (SF-26)	Changes in quality of life as a result of the dietary intervention will be assessed over a 6 month period using the SF-36. Items are scored so that a high score defines a more favorable health state, with each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively.	day 0 to 12 months

Collaborators and Investigators

• Sponsor: Loma Linda University
• Investigators: Principal Investigator: Brenda Bartnik-Olson, PhD, Loma Linda University Medical Center; Principal Investigator: Duc Tran, MD, Loma Linda University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2020
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: August 11, 2020
• First Submitted That Met QC Criteria: August 26, 2020
• First Posted (Actual): August 28, 2020

Study Record Updates

• Last Update Posted (Actual): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: ketogenic diet; traumatic brain injury; metabolism; cerebral blood flow; spectroscopy; modified Atkins diet
• 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: 5200137

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No