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

Trial Summary

What is the purpose of this trial?

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 traumatic brain injury (TBI). The secondary objective is a preliminary evaluation of the outcomes of children who have had the standard of care plus the KD, compared to those with standard of care alone. Outcome measures for the secondary objective will include: need for ventriculoperitoneal shunt, duration of unconsciousness, need for any type of craniotomy, duration of post-traumatic amnesia, acute hospitalization length of stay, and cognitive and motor function at 12 months after injury. If this study demonstrates feasibility and safety, the information related to outcomes will be used to inform the planning of a future, larger, randomized study of the efficacy of the KD in children and adolescents with TBI. Specifically, this information will be used to assist with sample size calculations for this future study.

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 data supports the effectiveness of the ketogenic diet treatment 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 metabolism and protecting brain cells. It has also been effective in reducing seizures in children with epilepsy, indicating its potential benefits for brain health. ^{1 2 3 4 5}

Is the ketogenic diet safe for use in humans, particularly in children?

The ketogenic diet has been used safely in children, especially for treating epilepsy, but care must be taken to avoid carbohydrate-containing medications in hospitals. Safety data for its use in traumatic brain injury is limited, but it has been studied in adults and animal models with some positive findings. ^{1 5 6 7 8}

How is the ketogenic diet treatment different for pediatric traumatic brain injury?

The ketogenic diet is unique for treating pediatric traumatic brain injury because it provides an alternative energy source for the brain by using fats instead of carbohydrates, which may protect brain cells and improve recovery. Unlike other treatments, it has shown potential in reducing brain cell damage and supporting brain repair, especially in younger patients. ^{1 2 5 6 9}

Research Team

Linda Krach, MD

Principal Investigator

Department of Physical Medicine and Rehabilitation

Angela Sinner, DO

Principal Investigator

Department of Physical Medicine and Rehabilitation

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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 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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase I single center trial of ketogenic diet for adults with traumatic brain injury. [2022]

2. United States 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. [2018]

3. Switzerland pubmed.ncbi.nlm.nih.gov

The Ketogenic Diet in the Treatment of Post-concussion Syndrome-A Feasibility Study. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Dietary treatments for epilepsy: management guidelines for the general practitioner. [2011]

5. England pubmed.ncbi.nlm.nih.gov

Ketogenic diet protects myelin and axons in diffuse axonal injury. [2022]

6. England pubmed.ncbi.nlm.nih.gov

The protective effect of the ketogenic diet on traumatic brain injury-induced cell death in juvenile rats. [2017]

7. United States pubmed.ncbi.nlm.nih.gov

Reducing Prescribing Errors in Hospitalized Children on the Ketogenic Diet. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Does ketogenic diet alter seizure sensitivity and cell loss following fluid percussion injury? [2017]

9. Australia pubmed.ncbi.nlm.nih.gov

A new ketogenic formulation improves functional outcome and reduces tissue loss following traumatic brain injury in adult mice. [2021]