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

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ClinicalTrials.gov Identifier: NCT04530032
Recruitment Status : Not yet recruiting
First Posted : August 28, 2020
Last Update Posted : October 5, 2020
Sponsor:
Information provided by (Responsible Party):
Brenda Bartnik Olson, PhD, Loma Linda University

Brief Summary:
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 short term (14 day) ketogenic diet on neurocognitive outcome following moderate-severe TBI.

Condition or disease Intervention/treatment Phase
Traumatic Brain Injury Other: ketogenic diet Other: Standard diet Not Applicable

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:

  1. 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.
  2. 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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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
Estimated Study Start Date : November 1, 2020
Estimated Primary Completion Date : June 30, 2022
Estimated Study Completion Date : December 30, 2022

Resource links provided by the National Library of Medicine


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 Name: modified Atkins diet

Sham Comparator: TBI SD
TBI subjects on a standard (normal) diet
Other: Standard diet
standard (normal) diet use




Primary Outcome Measures :
  1. Neurological outcome [ Time Frame: 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).

  2. Change in cerebral metabolism [ Time Frame: 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 :
  1. Neurocognitive outcome: Trail Making Test, Part B [ Time Frame: 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.

  2. Neurocognitive outcome: Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) [ Time Frame: 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.


  3. Neurocognitive outcome: Delis Kaplan Executive Function System (D-KEFS) [ Time Frame: 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.

  4. Neurocognitive outcome: 36 Item Short Form Survey (SF-26) [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04530032


Contacts
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Contact: Brenda Bartnik-Olson, PhD 909-558-4000 ext 85216 BBartnik@llu.edu
Contact: Duc Tran, MD 909-558-4000 ext 66273 dtran@llu.edu

Sponsors and Collaborators
Loma Linda University
Investigators
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Principal Investigator: Brenda Bartnik-Olson, PhD Loma LInda University Medical Center
Principal Investigator: Duc Tran, MD Loma LInda University Medical Center
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Responsible Party: Brenda Bartnik Olson, PhD, Associate Professor, Loma Linda University
ClinicalTrials.gov Identifier: NCT04530032    
Other Study ID Numbers: 5200137
First Posted: August 28, 2020    Key Record Dates
Last Update Posted: October 5, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Brenda Bartnik Olson, PhD, Loma Linda University:
traumatic brain injury
ketogenic diet
metabolism
spectroscopy
cerebral blood flow
Additional relevant MeSH terms:
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Brain Injuries
Brain Injuries, Traumatic
Wounds and Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System