Ketogenic Diet for Pediatric Traumatic Brain Injury

Recruiting at 1 trial location

Overseen By Angela Sinner, DO

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Gillette Children's Specialty Healthcare

Disqualifiers: Oral diet, Anoxia, Non-accidental TBI, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

21 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a ketogenic diet (a high-fat, low-carb eating plan) is safe and feasible for children with moderate to severe traumatic brain injuries. The researchers aim to determine if adding this diet to usual care can improve recovery outcomes, such as the length of hospital stays and cognitive function. Children who have experienced a traumatic brain injury and are not currently on an oral diet might be suitable candidates for this study. The trial will compare results with past patients who received standard care without the diet to gather data for future, larger studies. As an unphased trial, this study offers participants a unique opportunity to contribute to pioneering research that could shape future treatments.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that the ketogenic diet is safe for children with traumatic brain injury?

Research has shown that the ketogenic diet, high in fats and low in carbohydrates, has been studied for safety in children with brain injuries. Studies have not identified any serious safety issues with this diet. Previous tests have not revealed major safety problems, indicating it is generally well-tolerated. While more research is needed, current evidence suggests the ketogenic diet is a safe option for children recovering from brain injuries. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for pediatric traumatic brain injury, which often focus on surgery, medication, and rehabilitation therapies, the ketogenic diet offers a unique approach by altering the body's metabolism. This high-fat, low-carbohydrate diet encourages the body to use fat instead of glucose for energy, which may help reduce inflammation and provide an energy source for the brain when it's healing. Researchers are excited about this treatment because it could potentially enhance recovery and improve outcomes for young patients with brain injuries by tapping into the brain's ability to utilize ketones for fuel, offering a novel pathway to support brain healing.

What evidence suggests that the ketogenic diet might be an effective treatment for traumatic brain injury?

Studies have shown that the ketogenic diet, high in fats and low in carbohydrates, may aid recovery after brain injuries. Research using rats with traumatic brain injury (TBI) suggested that this diet can reduce brain damage and improve recovery. The diet helps brain cells use energy more effectively, which benefits recovery after an injury. Although studies in humans are limited, early results are promising for using the ketogenic diet to assist people with TBI. In this trial, participants in the prospective intervention group will receive a weight-based ketogenic diet for up to fourteen days, alongside standard care, to assess its potential to improve outcomes like thinking skills and movement abilities in children with moderate to severe brain injuries. ^{1 2 3 5 6}

Who Is on the Research Team?

Angela Sinner, DO

Principal Investigator

Department of Physical Medicine and Rehabilitation

Linda Krach, MD

Principal Investigator

Department of Physical Medicine and Rehabilitation

Are You a Good Fit for This Trial?

This trial is for children with moderate to severe traumatic brain injury, defined by a Glasgow Coma Scale Score of 3-12. It's open to those who are not on an oral diet and don't have conditions that would exclude them as per medical staff judgment. Children with non-accidental injuries or significant oxygen deprivation from near-drowning aren't eligible.

Inclusion Criteria

I was within the required age range when I got injured and admitted.

I had a severe head injury with a low Glasgow Coma Scale score.

Exclusion Criteria

Any condition that in the opinion of the Pediatric Intensive Care Unit or neurosurgery medical staff warrants exclusion from the study

Non-accidental traumatic brain injury (i.e., assault, abuse)

Penetrating injury including gunshot wounds

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive standard of care for acute management of moderate to severe traumatic brain injury, together with a weight-based ketogenic diet added for up to fourteen days

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including cognitive and motor function at 12 months after injury

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Ketogenic Diet

Trial Overview The study tests the safety and feasibility of a ketogenic diet in addition to standard care for pediatric TBI compared to standard care alone. Outcomes like recovery time, cognitive function, and hospital stay length will be measured to plan future larger trials.

How Is the Trial Designed?

Group I: Prospective Intervention Group Experimental Treatment 1 Intervention

Participants will receive standard of care for acute management of moderate to severe traumatic brain injury, together with a weight-based ketogenic diet added for up to fourteen days.

Group II: Historical Control Group Active Control 1 Intervention

Medical records of past TBI patients will be used as controls matched for age, gender, socioeconomic status (type of health care coverage including private insurance vs. government-funded coverage), lowest first 24 hour post-injury Glasgow Coma Score (GCS) (\<8 or 8-12), and pre-injury school program (regular or special education).

Who Is Running the Clinical Trial?

Gillette Children's Specialty Healthcare

Lead Sponsor

Trials

31

Recruited

8,100+

State of Minnesota Spinal Cord Injury and Traumatic Brain Injury Research Grant Program

Collaborator

Trials

1

Recruited

20+

Children's Minnesota

Collaborator

Trials

1

Recruited

20+

Published Research Related to This Trial

Rats with diffuse axonal injury (DAI) that were fed a ketogenic diet showed reduced demyelination and less axonal damage, suggesting that ketone bodies can protect myelin and support recovery after brain injury.

In laboratory tests, the ketone body β-hydroxybutyrate (βHB) improved myelination and cell survival in oligodendrocytes, indicating its potential as a therapeutic agent for preventing damage in brain injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic diet protects myelin and axons in diffuse axonal injury. Mu, J., Wang, T., Li, M., et al.[2022]

A pilot study involving 14 participants with post-concussion syndrome (PCS) tested a ketogenic diet (KD) for 2 months, showing that 11 participants successfully achieved ketosis and reported improvements in visual memory and symptom scores.

The ketogenic diet was found to be a feasible treatment option for PCS, with some participants experiencing symptom relief, although further research is needed to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Ketogenic Diet in the Treatment of Post-concussion Syndrome-A Feasibility Study. Rippee, MA., Chen, J., Taylor, MK.[2020]

In a rat model of traumatic brain injury (TBI), the ketogenic diet (KD) increased the seizure threshold, meaning rats on the KD took longer to have seizures compared to those on a standard diet, particularly when the KD was maintained during seizure testing.

However, while KD reduced neuronal cell loss in the brain when administered before TBI, it did not prevent the development of epilepsy after the injury, indicating that KD may not be effective as a long-term antiepileptogenic treatment in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does ketogenic diet alter seizure sensitivity and cell loss following fluid percussion injury? Schwartzkroin, PA., Wenzel, HJ., Lyeth, BG., et al.[2017]

A new ketogenic diet (KD) designed for adults significantly improved recovery from traumatic brain injury (TBI) in mice, showing reduced sensorimotor deficits and improved spatial memory over a 70-day study period.

The new-KD increased levels of Beta-hydroxybutyrate (β-HB) and enhanced the mTOR pathway, leading to reduced inflammation and tissue damage, suggesting it has therapeutic potential for treating TBI in adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new ketogenic formulation improves functional outcome and reduces tissue loss following traumatic brain injury in adult mice. Thau-Zuchman, O., Svendsen, L., Dyall, SC., et al.[2021]

A clinical decision support alert significantly reduced the prescription of carbohydrate-containing medications in hospitalized children on a ketogenic diet, decreasing orders from 0.69 to 0.35 per patient-day, which prevented 256 inappropriate orders.

The alert was accepted 57% of the time when it fired, demonstrating that user-centered design can effectively influence prescriber behavior and enhance patient safety without overwhelming healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reducing Prescribing Errors in Hospitalized Children on the Ketogenic Diet. Siegel, BI., Johnson, M., Dawson, TE., et al.[2021]

In a pilot study involving 10 adult male patients with traumatic brain injury (TBI), the ketogenic diet (KD) was found to be feasible, with 80% of participants achieving ketosis within an average of 2.2 days after starting the diet.

No significant clinical adverse effects were reported, although some patients experienced mild issues like hypertriglyceridemia and hypoglycemia, suggesting that KD may be a safe intervention for TBI management, warranting further investigation in a randomized controlled trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I single center trial of ketogenic diet for adults with traumatic brain injury. Arora, N., Litofsky, NS., Golzy, M., et al.[2022]

In a study involving 60 male Sprague-Dawley rats, the ketogenic diet (KD) significantly reduced brain edema and cellular apoptosis after traumatic brain injury (TBI), indicating its potential neuroprotective effects.

The KD was found to lower levels of the pro-apoptotic protein Bax, suggesting that it may help mitigate cell death in the brain following TBI, which could be beneficial for pediatric patients suffering from such injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The protective effect of the ketogenic diet on traumatic brain injury-induced cell death in juvenile rats. Hu, ZG., Wang, HD., Qiao, L., et al.[2017]

A ketogenic diet (KD) significantly increased levels of beta-hydroxybutyrate and improved motor performance in rats after repetitive mild traumatic brain injury (rmTBI), indicating its potential efficacy in enhancing recovery.

KD therapy also prevented brain edema and improved neurochemical metabolite ratios, suggesting a protective role against neurodegeneration following rmTBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton Magnetic Resonance Spectroscopy (H1-MRS) Study of the Ketogenic Diet on Repetitive Mild Traumatic Brain Injury in Adolescent Rats and Its Effect on Neurodegeneration. Zhang, F., Wu, H., Jin, Y., et al.[2018]

Ketogenic diets, including various forms like the classic ketogenic diet and modified Atkins diet, can lead to a significant reduction in seizures for 30-60% of children after 6 months of treatment, making them an effective option for managing epilepsy.

Despite their efficacy, these dietary therapies come with potential side effects and require strict adherence, which may not be feasible for all families, highlighting the need for careful consideration and support from healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary treatments for epilepsy: management guidelines for the general practitioner. Lee, PR., Kossoff, EH.[2011]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK209323/

Ketogenic Diet - Nutrition and Traumatic Brain Injury - NCBI Studies with a rat model of TBI have suggested reduction in volume of damage and improved recovery with use of the ketogenic diet (Prins, 2008). One study ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04933448

Ketogenic Diet Following Moderate to Severe Pediatric ... The primary objective of this study is to evaluate the feasibility and safety of using the ketogenic diet (KD) in children who sustained moderate to severe ...

3. withpower.com withpower.com/trial/phase-brain-injuries-7-2021-ebd27

Ketogenic Diet for Pediatric Traumatic Brain Injury Research suggests that a ketogenic diet, which is high in fats and low in carbohydrates, can improve recovery after brain injuries by enhancing cellular ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2319417020300081

Application of ketogenic diets for pediatric neurocritical care Many studies have shown that a ketogenic diet is an effective treatment therapy for traumatic brain injuries in rat models. Multiple mechanisms by which a ...

5. nap.nationalacademies.org nap.nationalacademies.org/read/13121/chapter/15

11 Ketogenic Diet | Nutrition and Traumatic Brain Injury CONCLUSIONS AND RECOMMENDATIONS. Based on the evidence presented, the ketogenic diet does hold some promise of effectiveness in improving the outcomes of TBI.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7681084/

A new ketogenic formulation improves functional outcome and ... A new ketogenic formulation improves functional outcome and reduces tissue loss following traumatic brain injury in adult mice.