Clinical trial NCT04530032: Ketogenic Diet & Functional Recovery in Moderate to Severe Traumatic Brain Injury
Official title: Ketogenic Diet & Functional Recovery in Moderate to Severe Traumatic Brain Injury
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Traumatic Brain Injury
Keywords: traumatic brain injury
ketogenic diet
metabolism
spectroscopy
cerebral blood flow
modified Atkins diet
Lead sponsor: Loma Linda University
Sponsor class: OTHER
First posted: 2020-08-28
Enrollment: 30
Sex: ALL
Minimum age (years): 16
Maximum age (years): 90
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 a ketogenic or modified Atkins diet on neurocognitive outcome following moderate-severe TBI.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Neurological outcome
timeFrame: day 0 to 12 months
measure: Change in cerebral metabolism
timeFrame: day 0 to 12 months
Secondary outcomes:
measure: Neurocognitive outcome: Trail Making Test, Part B
timeFrame: day 0 to 12 months
measure: Neurocognitive outcome: Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
timeFrame: day 0 to 12 months
measure: Neurocognitive outcome: Delis Kaplan Executive Function System (D-KEFS)
timeFrame: day 0 to 12 months
measure: Neurocognitive outcome: 36 Item Short Form Survey (SF-26)
timeFrame: day 0 to 12 months
Other outcomes:
Locations:
city: Loma Linda
country: United States
facility: Loma Linda University Health
state: California
Study officials:
affiliation: Loma LInda University Medical Center
name: Brenda Bartnik-Olson, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Loma LInda University Medical Center
name: Duc Tran, MD
role: PRINCIPAL_INVESTIGATOR
References: