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

Sponsor

Loma Linda University (Other)

Overall Status

Enrolling by invitation

CT.gov ID

NCT04530032

Collaborator

(none)

Enrollment

Location

Arms

24.7

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Condition or Disease	Intervention/Treatment	Phase
Traumatic Brain Injury	Other: ketogenic diet Other: Standard diet	N/A

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) 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 a short term (14 day) KD on 6 month outcome following moderate-severe TBI patients.

The purpose of this project is to:

Determine the effect of KD 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 short-term KD 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.
Identify the effect of KD 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 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 Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 7, 2020

Anticipated Primary Completion Date :

Jun 30, 2022

Anticipated Study Completion Date :

Dec 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TBI KD TBI subjects on a ketogenic diet	Other: ketogenic diet short term (18 day) ketogenic/modified atkins diet use Other Names: modified Atkins diet
Sham Comparator: TBI SD TBI subjects on a standard (normal) diet	Other: Standard diet standard (normal) diet use

Arm

Intervention/Treatment

Experimental: TBI KD

TBI subjects on a ketogenic diet

Other: ketogenic diet

short term (18 day) ketogenic/modified atkins diet use

Other Names:

modified Atkins diet

Sham Comparator: TBI SD

TBI subjects on a standard (normal) diet

Other: Standard diet

standard (normal) diet use

Outcome Measures

Primary Outcome Measures

Neurological outcome [day 0 to 6 months]
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).
Change in cerebral metabolism [day 0 to 6 months]
Single voxel magnetic resonance spectroscopy will be used to assess changes in cerebral metabolism as a result of the dietary intervention.

Secondary Outcome Measures

Neurocognitive outcome: Trail Making Test, Part B [day 0 to 6 months]
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.
Neurocognitive outcome: Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) [day 0 to 6 months]
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.
Neurocognitive outcome: Delis Kaplan Executive Function System (D-KEFS) [day 0 to 6 months]
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.
Neurocognitive outcome: 36 Item Short Form Survey (SF-26) [day 0 to 6 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Moderate (GCS 9 - 12) to severe (GCS ≤ 8) traumatic brain injury (TBI) between 2-30 days post injury
Admitted to acute inpatient rehabilitation, LLU East Campus unit 1100

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
known history of dialysis, liver dysfunction, dyslipidemia, vitamin D deficiency, or
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
history of uncontrolled hyperglycemia or diabetes
Metal, implanted device, pregnancy, claustrophobia, or other contraindication to MRI

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Loma Linda University Health	Loma Linda	California	United States	92354

Sponsors and Collaborators

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