Ketogenic Diet to Improve Neuro-recovery

NCT ID: NCT03509571

Last Updated: 2025-07-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-09
• Study Completion Date: 2026-01-01

Brief Summary

The purpose of this project is to determine if 5 weeks of ketogenic (KD, high-fat) diet vs. standard diet (SD) significantly improves motor and sensory function, glycemic function, and functional independence in patients with spinal cord injury.

Detailed Description

There is an urgent need for innovative therapies for improving neurorecovery after spinal cord injury (SCI). Despite extensive research, clinical advancements, and improved rehabilitation strategies, SCI continues to be a significant cause of disability and mortality. After a primary impact, the injured spinal cord undergoes multiple secondary pathological states that represent an important target in developing neuroprotective strategies for treatment of SCI. Even minor improvements in neurological recovery can have profound impacts on management of daily activities, secondary health complications, and quality of life. Thus, timely and effective strategies are of critical importance for positive outcomes after SCI. A number of pharmacological neuroprotective agents have been subject to intensive investigation in large, multicenter, prospective randomized controlled trials. Despite promising preclinical animal data, the primary outcomes of these clinical trials were largely negative. There is thus clear reason for researchers, clinicians, and patients to seek alternative therapies to enhance neurorecovery and functional status after SCI.

The scientific premise of this project rests upon accumulating evidence that diet-based therapies, such as the ketogenic diet (KD), offer effective neuroprotection against secondary injury cascades and improve forelimb motor function in a rat model of SCI and improve upper extremity motor function in patients with acute SCI. The KD is a high-fat, low-carbohydrate diet designed to mimic the metabolic and biochemical changes that occur during calorie restriction, specifically ketosis. Ketone bodies have been shown to exert neuroprotective effects by preventing oxidative damage; attenuating neuroinflammation and glutamate excitotoxicity; and inhibiting apoptosis in the brain and spinal cord. Because glutamate excitotoxicity, inflammation, and induction of apoptotic pathways lead to progressive degeneration in the spinal cord shortly after the injury, inhibition of these processes by ketone bodies may enhance neurological recovery after an SCI. In support of these hypotheses, we recently showed for the first time that, compared with a standard hospital diet (SD), 5 weeks of KD improved upper extremity motor function in patients with acute SCI. In addition, a neuroinflammatory blood protein, fibrinogen, was present at lower levels in the KD serum samples than in the SD serum samples. Taken together, our results suggest that a KD may induce anti-inflammatory effects in part by reducing fibrinogen, which promotes neuroprotection and improved recovery.

The acute stage post-SCI is also characterized by hyperglycemia, which is strongly associated with poor functional outcomes at discharge. These findings support the importance of achieving tight glycemic control in acute human SCI to obtain better neurological outcomes. Emerging evidence suggests that a KD can also improve the patient's metabolic state and maintain normal glycemic levels. In contrast, standard hospital diets have traditionally promoted a relatively high carbohydrate nutritional content. Consistent with previous findings, we have recently shown that 5 weeks of KD decreased fasting serum glucose levels by 24 mg/dl whereas levels increased by 0.7 mg/dl in the SD group. These provocative findings have led us to our central hypothesis that SCI patients who consume a KD over the first 5 weeks (average hospital stay) after injury will have better neurological recovery, functional independence, and glycemic control than the SCI patients who consume an SD during this period.

Conditions

Spinal Cord Injuries

Study Design

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

Study Groups

Ketogenic Diet Group

Ketogenic diet is a high-fat, low-carbohydrate diet (lipid to carbohydrate + protein ratio of 3:1) that included ≈72% total energy as fat, ≈25% as protein, and ≈3% as carbohydrate during enteral feeding and ≈65% total energy as fat, ≈27% as protein, and ≈8% as carbohydrate and fiber during solid feeding. Patients will start receiving ketogenic diet within the 72 hours injury, after completing their baseline measurements.

Group Type: EXPERIMENTAL

Ketogenic Diet

Intervention Type: OTHER

Enteral feeding via nasogastric (NG) or nasojejunal (NJ) tubes with ketogenic diet will start within 72 hours of injury and solid feeding will start as soon as the patient is able to swallow. This diet is a high-fat, low-carbohydrate diet (lipid to carbohydrate + protein ratio of 3:1) that will include ≈75% total energy as fat, ≈20% as protein, and ≈5% as carbohydrate and fiber.

Standard Diet Group

Patients will start to receive standard hospital diet within 72 hours of injury after completing their baseline measurements. Standard diet includes ≈35% total energy as fat, ≈27% as protein, and ≈44% as carbohydrate and fiber.

Group Type: OTHER

Standard Diet

Intervention Type: OTHER

Enteral feeding via nasogastric (NG) or nasojejunal (NJ) tubes with SD diet will start within 72 hours of injury and solid feeding will start as soon as the patient is able to swallow. This diet includes ≈35% total energy as fat, ≈27% as protein, and ≈44% as carbohydrate and fiber.

Interventions

Ketogenic Diet

Enteral feeding via nasogastric (NG) or nasojejunal (NJ) tubes with ketogenic diet will start within 72 hours of injury and solid feeding will start as soon as the patient is able to swallow. This diet is a high-fat, low-carbohydrate diet (lipid to carbohydrate + protein ratio of 3:1) that will include ≈75% total energy as fat, ≈20% as protein, and ≈5% as carbohydrate and fiber.

Intervention Type: OTHER

Standard Diet

Enteral feeding via nasogastric (NG) or nasojejunal (NJ) tubes with SD diet will start within 72 hours of injury and solid feeding will start as soon as the patient is able to swallow. This diet includes ≈35% total energy as fat, ≈27% as protein, and ≈44% as carbohydrate and fiber.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Clinically motor complete and incomplete spinal cord injury, age 19-60
• ASIA A, B, C or D (ASIA: Neurological Impairment Scale)

Exclusion Criteria

• Pregnant women.
• Neurological (other than SCI), vascular and/or cardiac problems that may limit function and interfere with testing procedures
• Patients with evidence of renal insufficiency and liver disease by history, physical examination, and laboratory tests
• Patients with underlying pulmonary diseases

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ohio State University

OTHER

Sponsor Role: lead

Responsible Party

Ceren Yarar-Fisher

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ceren Yarar-Fisher, PhD

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Raquel Minarsch, DPT

Role: STUDY_DIRECTOR

Ohio State University

Locations

Ohio State University Hospital

Columbus, Ohio, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Ceren Yarar-Fisher, PhD

Role: CONTACT

yarar-fisher.1@osu.edu

205-977-0891

Raquel Minarsch, DPT

Role: CONTACT

raquel.minarsch@osumc.edu

330-881-1710

Facility Contacts

Ceren Yarar-Fisher, PhD

Role: primary

References

Demirel A, Li J, Morrow C, Barnes S, Jansen J, Gower B, Kirksey K, Redden D, Yarar-Fisher C. Evaluation of a ketogenic diet for improvement of neurological recovery in individuals with acute spinal cord injury: study protocol for a randomized controlled trial. Trials. 2020 May 4;21(1):372. doi: 10.1186/s13063-020-04273-7.

Reference Type: DERIVED

PMID: 32366293 (View on PubMed)

Other Identifiers

1R01NR016443-01A1

Identifier Type: NIH

Identifier Source: org_study_id

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