Ketogenic Diet for Pediatric Traumatic Brain Injury
Recruiting in Palo Alto (17 mi)
+1 other location
Overseen byLinda Krach, MD
Age: < 18
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Gillette Children's Specialty Healthcare
Disqualifiers: Oral diet, Anoxia, Non-accidental TBI, others
No Placebo Group
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.
12345Is 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.
15678How 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.
12569Eligibility 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
+3 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: Prospective Intervention GroupExperimental Treatment1 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 GroupActive Control1 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).
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Children's MinnesotaMinneapolis, MN
Gillette Children's Specialty HealthcareMinneapolis, MN
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Who Is Running the Clinical Trial?
Gillette Children's Specialty HealthcareLead Sponsor
State of Minnesota Spinal Cord Injury and Traumatic Brain Injury Research Grant ProgramCollaborator
Children's MinnesotaCollaborator
References
Phase I single center trial of ketogenic diet for adults with traumatic brain injury. [2022]Traumatic Brain injury (TBI) is a major cause of mortality and morbidity in the United States. Ketogenic diet (KD) has been shown to have neuroprotective effects in acute brain injury, but limited data about its use in adult TBI patients is available. The objective of this study is to investigate the feasibility and safety of ketogenic diet (KD) for adult TBI patients in the Neuroscience Intensive Care Unit (NSICU).
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]A ketogenic diet (KD) improves cellular metabolism and functional recovery after moderate-to-severe traumatic brain injury. Here, we evaluated the changes of neurochemical metabolites after KD therapy for repetitive mild traumatic brain injury (rmTBI) and its possible role in neurodegeneration.
The Ketogenic Diet in the Treatment of Post-concussion Syndrome-A Feasibility Study. [2020]Concussion is the most common form of mild traumatic brain injury (mTBI). Although most patients' symptoms resolve within a month, patients with post-concussion syndrome (PCS) may continue to experience symptoms for years and have limited treatment options. This pilot study assessed the feasibility and symptom-related effects of a ketogenic diet (KD) in patients with PCS symptoms. The Ketogenic Diet in Post-Concussion Syndrome (KD-PCS) was a single-arm trial of a 2-month KD high in non-starchy vegetables and supplemented with medium-chain triglyceride (MCT) oil. Macronutrient targets were ≥70% fat, ≤10% carbohydrate, and the remainder as protein as energy. We assessed feasibility by daily self-reported measure of urine acetoacetate and collection of 3-day food records and serum beta-hydroxybutyrate at multiple timepoints. We assessed symptoms by administering the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) and Modified Balance Error Scoring System (M-BESS) at baseline and month 2 and the Post-Concussion Symptom Scale (PCSS) at baseline, month 1, and month 2. Fourteen participants enrolled in the KD-PCS. Twelve participants completed the study and 11 implemented the KD (73% fat, 9% carbohydrate, and 18% protein) and achieved ketosis. One participant complained of MCT-related diarrhea that resolved and another reported nausea and fatigue that resulted in withdrawal from the study. Among compliant participants, the visual memory domain of the ImPACT improved by 12 points (p = 0.02) and PCSS scores improved by 9 points, although not statistically significant. This pilot trial suggests that the KD is a feasible experimental treatment for PCS and justifies further study of its efficacy.
Dietary treatments for epilepsy: management guidelines for the general practitioner. [2011]As ketogenic diets become more frequently used as a standard treatment for epilepsy in children and adults, hospital and community neurologists, pediatricians, intensivists, general practitioners, and house officers will readily encounter patients who are receiving these dietary treatments. A growing body of evidence demonstrates that dietary therapies for epilepsy (classic ketogenic diet, medium-chain triglyceride diet, modified Atkins diet, and low-glycemic-index treatment) are highly effective, with approximately 30-60% of children overall having at least a 50% reduction in seizures after 6 months of treatment. However, as would be true of any other medical anticonvulsant therapy, these treatments have known side effects and complications requiring recognition and timely action. In addition, the ketogenic diet is a significant intervention requiring rigorous daily adherence; not every family is willing or able to make the necessary commitment to this therapy. We provide herein a survey of the most common situations faced in both the inpatient and outpatient settings, including a discussion of triage and management based on our center's experience as well as the recent 2009 International Consensus Guideline.
Ketogenic diet protects myelin and axons in diffuse axonal injury. [2022]Ketogenic diet (KD) has been identified as a potential therapy to enhance recovery after traumatic brain injury (TBI). Diffuse axonal injury (DAI) is a common type of traumatic brain injury that is characterized by delayed axonal disconnection. Previous studies showed that demyelination resulting from oligodendrocyte damage contributes to axonal degeneration in DAI.
The protective effect of the ketogenic diet on traumatic brain injury-induced cell death in juvenile rats. [2017]The ketogenic diet (the KD) is an effective treatment for intractable epilepsy, especially in the paediatric population, and a growing number of studies have shown the neuroprotective role of the KD. However, few studies focused on the neuroprotective effects of the KD in traumatic brain injury (TBI). The present study aimed to investigate the effects of the KD on TBI.
Reducing Prescribing Errors in Hospitalized Children on the Ketogenic Diet. [2021]Children on the ketogenic diet must limit carbohydrate intake to maintain ketosis and reduce seizure burden. Patients on ketogenic diet are vulnerable to harm in the hospital setting where carbohydrate-containing medications are commonly prescribed. We developed clinical decision support to reduce inappropriate prescription of carbohydrate-containing medications in hospitalized children on ketogenic diet.
Does ketogenic diet alter seizure sensitivity and cell loss following fluid percussion injury? [2017]Traumatic brain injury (TBI) frequently leads to epilepsy. The process of epileptogenesis - the development of that seizure state - is still poorly understood, and effective antiepileptogenic treatments have yet to be identified. The ketogenic diet (KD) has been shown to be effective as an antiepileptic therapy, but has not been extensively tested for its efficacy in preventing the development of the seizure state, and certainly not within the context of TBI-induced epileptogenesis. We have used a rat model of TBI - fluid percussion injury (FPI) - to test the hypothesis that KD treatment is antiepileptogenic and protects the brain from neuronal cell loss following TBI. Rats fed a KD had a higher seizure threshold (longer latency to flurothyl-induced seizure activity) than rats fed a standard diet (SD); this effect was seen when KD was in place at the time of seizure testing (3 and 6 weeks following FPI), but was absent when KD had been replaced by SD at time of testing. FPI caused significant hippocampal cell loss in both KD-fed and SD-fed rats; the degree of cell loss appeared to be reduced by KD treatment before FPI but not after FPI. These results are consistent with prior demonstrations that KD raises seizure threshold, but do not provide support for the hypothesis that KD administered for a limited time directly before or after FPI alters later seizure sensitivity; that is, within the limits of this model and protocol, there is no evidence for KD-induced antiepileptogenesis.
A new ketogenic formulation improves functional outcome and reduces tissue loss following traumatic brain injury in adult mice. [2021]Rationale: Traumatic brain injury (TBI) leads to neurological impairment, with no satisfactory treatments available. Classical ketogenic diets (KD), which reduce reliance on carbohydrates and provide ketones as fuel, have neuroprotective potential, but their high fat content reduces compliance, and experimental evidence suggests they protect juvenile brain against TBI, but not adult brain, which would strongly limit their applicability in TBI. Methods: We designed a new-KD with a fat to carbohydrate plus protein ratio of 2:1, containing medium chain triglycerides (MCT), docosahexaenoic acid (DHA), low glycaemic index carbohydrates, fibres and the ketogenic amino acid leucine, and evaluated its neuroprotective potential in adult TBI. Adult male C57BL6 mice were injured by controlled cortical impact (CCI) and assessed for 70 days, during which they received a control diet or the new-KD. Results: The new-KD, that markedly increased plasma Beta-hydroxybutyrate (β-HB), significantly attenuated sensorimotor deficits and corrected spatial memory deficit. The lesion size, perilesional inflammation and oxidation were markedly reduced. Oligodendrocyte loss appeared to be significantly reduced. TBI activated the mTOR pathway and the new-KD enhanced this increase and increased histone acetylation and methylation. Conclusion: The behavioural improvement and tissue protection provide proof of principle that this new formulation has therapeutic potential in adult TBI.