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

NCT ID: NCT04530032

Last Updated: 2026-02-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-07
• Study Completion Date: 2025-08-14

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.

Conditions

Traumatic Brain Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

TBI KD/MAD

TBI subjects on a ketogenic/modified Atkins diet

Group Type: EXPERIMENTAL

ketogenic/modified Atkins diet

Intervention Type: OTHER

ketogenic/modified Atkins diet use

TBI SD

TBI subjects on a standard (normal) diet

Group Type: SHAM_COMPARATOR

Standard diet

Intervention Type: OTHER

standard (normal) diet use

Interventions

ketogenic/modified Atkins diet

ketogenic/modified Atkins diet use

Intervention Type: OTHER

Standard diet

standard (normal) diet use

Intervention Type: OTHER

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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Loma Linda University

OTHER

Sponsor Role: lead

Responsible Party

Brenda Bartnik Olson, PhD

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Brenda Bartnik-Olson, PhD

Role: PRINCIPAL_INVESTIGATOR

Loma LInda University Medical Center

Duc Tran, MD

Role: PRINCIPAL_INVESTIGATOR

Loma LInda University Medical Center

Locations

Loma Linda University Health

Loma Linda, California, United States

Countries

United States

Other Identifiers

5200137

Identifier Type: -

Identifier Source: org_study_id