Ketamine for Traumatic Brain Injury
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: University of Texas Southwestern Medical Center
Disqualifiers: Schizophrenia, Hypertension, Tachycardia, others
No Placebo Group
Approved in 5 Jurisdictions
Trial Summary
What is the purpose of this trial?
Traumatic brain injury (TBI) accounts for approximately 2.5 million visits to emergency departments in the United States each year. After decades of research, management strategies for severe TBI (sTBI) patients are still evolving. Optimizing intracranial pressure (ICP) and cerebral perfusion pressure (CPP) are paramount in the management of these patients and placement of these monitors is the current standard-of-care. However, monitoring brain oxygenation (PbtO2) with invasive intraparenchymal monitors is currently under investigation in the management of severe TBI and placement of these monitors is gaining widespread use. This has opened the door for the use of tiered therapy to optimize ICP and PbtO2 simultaneously. Current evidence indicates that correction of ICP, CPP and PbtO2 in sTBI requires optimized analgesia and sedation. Ketamine is one of the few drugs available that has both sedative and analgesic properties and does not commonly compromise respiratory drive like opioids and sedative-hypnotics. However, traditionally, ketamine has been viewed as contraindicated in the setting of TBI due to concerns for elevation in ICP. Yet, new data has cast this long-held assumption into significant doubt. Hence the present pilot study will characterize the neurophysiological response to a single dose of ketamine in critically-ill TBI patient with ICP and PbtO2 monitoring.
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 evidence supports the effectiveness of ketamine for treating traumatic brain injury?
Research suggests that ketamine may be safe for use in patients with brain injuries, as it does not increase intracranial pressure and may improve blood flow to the brain. Additionally, ketamine has shown protective effects on the brain in laboratory studies, which could be beneficial after a brain injury.12345
Is ketamine generally safe for humans?
How does the drug ketamine differ from other treatments for traumatic brain injury?
Ketamine is unique for traumatic brain injury because it can improve blood flow to the brain and has anti-inflammatory properties, which may help in recovery. Unlike other treatments, ketamine can be used safely without increasing pressure in the brain when administered under controlled conditions.12111213
Research Team
AB
Anna Bashmakov, D.O.
Principal Investigator
UT Southwestern Medical Center
Eligibility Criteria
This trial is for adults over 18 with severe traumatic brain injury (sTBI) who have had a device placed to monitor intracranial pressure and brain tissue oxygenation. It's not suitable for those who don't meet these specific conditions.Inclusion Criteria
I have had a severe brain injury.
I am 18 years old or older.
I have a device in my head to monitor brain pressure and oxygen levels.
Exclusion Criteria
Systolic blood pressure > 180, diastolic blood pressure > 120
Documented history of schizophrenia
Sinus tachycardia with sustained heart rate >120
See 5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
1-2 weeks
Treatment
Participants receive a single dose of ketamine to assess neurophysiological response in severe TBI patients
1 day
1 visit (in-person)
Monitoring
Participants are monitored for brain tissue oxygenation and intracranial pressure for 3 hours post-treatment
3 hours
Continuous monitoring
Follow-up
Participants are monitored for safety and effectiveness after treatment
1-2 weeks
Treatment Details
Interventions
- Ketamine (Dissociative Anesthetic)
Trial OverviewThe study is testing the effects of a single dose of ketamine on patients with sTBI. Ketamine, known for its sedative and pain-relieving properties, will be evaluated to see how it affects brain pressure and oxygen levels in critically ill TBI patients.
Ketamine is already approved in United States, European Union, United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Ketalar for:
- Anesthesia
- Treatment-resistant depression
🇪🇺 Approved in European Union as Ketalar for:
- Anesthesia
- Treatment-resistant depression
🇺🇸 Approved in United States as Spravato for:
- Treatment-resistant depression
🇪🇺 Approved in European Union as Spravato for:
- Treatment-resistant depression
🇨🇦 Approved in Canada as Spravato for:
- Treatment-resistant depression
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Parkland Memorial HospitalDallas, TX
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Who Is Running the Clinical Trial?
University of Texas Southwestern Medical Center
Lead Sponsor
Trials
1102
Patients Recruited
1,077,000+
References
[Animal experiment of the ketamine effects on traumatic brain injury resulting from impact maxillofacial injury]. [2013]To test the effects of ketamine (KET) on traumatic brain injury resulting from impact maxillofacial injury.
Revising a dogma: ketamine for patients with neurological injury? [2022]We evaluated reports of randomized clinical trials in the perioperative and intensive care setting concerning ketamine's effects on the brain in patients with, or at risk for, neurological injury. We also reviewed other studies in humans on the drug's effects on the brain, and reports that examined ketamine in experimental brain injury. In the clinical setting, level II evidence indicates that ketamine does not increase intracranial pressure when used under conditions of controlled ventilation, coadministration of a gamma-aminobutyric acid (GABA) receptor agonist, and without nitrous oxide. Ketamine may thus safely be used in neurologically impaired patients. Compared with other anesthetics or sedatives, level II and III evidence indicates that hemodynamic stimulation induced by ketamine may improve cerebral perfusion; this could make the drug a preferred choice in sedative regimes after brain injury. In the laboratory, ketamine has neuroprotective, and S(+)-ketamine additional neuroregenerative effects, even when administered after onset of a cerebral insult. However, improved outcomes were only reported in studies with brief recovery observation intervals. In developing animals, and in certain brain areas of adult rats without cerebral injury, neurotoxic effects were noted after large-dose ketamine. These were prevented by coadministration of GABA receptor agonists.
Ketamine in acute phase of severe traumatic brain injury "an old drug for new uses?" [2021]Maintaining an adequate level of sedation and analgesia plays a key role in the management of traumatic brain injury (TBI). To date, it is unclear which drug or combination of drugs is most effective in achieving these goals. Ketamine is an agent with attractive pharmacological and pharmacokinetics characteristics. Current evidence shows that ketamine does not increase and may instead decrease intracranial pressure, and its safety profile makes it a reliable tool in the prehospital environment. In this point of view, we discuss different aspects of the use of ketamine in the acute phase of TBI, with its potential benefits and pitfalls.
Ketamine Administration in Prehospital Combat Injured Patients With Traumatic Brain Injury: A 10-Year Report of Survival. [2020]Background The Tactical Combat Casualty Care (TCCC) guidelines recommend ketamine as the primary battlefield analgesic in the setting of moderate-to-severe pain and hemodynamic compromise. However, despite recent studies failing to support the association between ketamine and worse outcomes in head trauma, TCCC guidelines state that ketamine may worsen severe traumatic brain injury. We compared mortality outcomes following head trauma sustained in a combat setting between ketamine recipients and non-recipients. Methods This is a secondary analysis of previously published data in the Department of Defense Trauma Registry from January 2007 to August 2016. We isolated patients with an abbreviated injury scale of 3 or greater for the head body region. We compared mortality between prehospital ketamine recipients and non-recipients. Results Our initial search yielded 28,222 patients, of which 4,183 met the inclusion criteria: 209 were ketamine-recipients and 3,974 were non-recipients. The ketamine group had a higher percentage injured by explosives (59.81% vs. 53.57%, p
Oral Ketamine for Depression, 1: Pharmacologic Considerations and Clinical Evidence. [2019]Clinical evidence is accumulating to support the use of ketamine as a powerful, quick-acting intervention for depression. Ketamine has been administered by oral, sublingual, transmucosal, intravenous, intramuscular, subcutaneous, intranasal, and even rectal routes. Whereas intravenous ketamine is the best studied approach, common sense dictates that oral ketamine is the most practical. The bioavailability of oral ketamine and interindividual variations thereof have been poorly studied; possibly only 20%-25% of an oral dose reaches the bloodstream. This is not necessarily a limitation because, as with other drugs that have poor oral bioavailability, compensation is possible by administering an appropriately higher dose, and interindividual variations can be addressed through individualized dose up-titration. A quarter- century of experience supports the use of oral ketamine for treating acute and chronic pain in children and adults. Case reports, case series, chart reviews, and 3 recent randomized controlled trials (RCTs) show that oral ketamine is effective in treating severe depression, depression with suicidal ideation, and treatment-resistant depression; that oral ketamine, used as an augmentation agent, improves outcomes in patients receiving a conventional antidepressant; and that oral ketamine reduces depression in patients with chronic pain. Doses of oral ketamine have ranged from 0.25 to 7 mg/kg and from 50 mg per occasion to 300 mg per occasion in multiple daily dosing, daily dosing, and intermittent dosing schedules. Oral ketamine was well tolerated in all studies; dropout and reasons for dropout were similar in ketamine and control arms in the 3 RCTs. These findings suggest that if ketamine is to find a place as an off-label treatment for depression and suicidality in mainstream psychiatry, researchers should study the safety, efficacy, and optimization of oral ketamine. Intravenous and intranasal routes may be monetarily more promising, but the oral route could be of greatest service.
A retrospective analysis of ketamine administration by critical care paramedics in a pre-hospital care setting. [2022]This project aims to describe pre-hospital use of ketamine in trauma by South East Coast Ambulance Service critical care paramedics and evaluate the occurrence of any side effects or adverse events.
Safety and efficacy of extended release ketamine tablets in patients with treatment-resistant depression and anxiety: open label pilot study. [2022]Ketamine's defining side effects are dissociation and increased blood pressure/heart rate. An oral formulation with delayed absorption could minimize these effects. We recently reported safety and tolerability data for an extended release ketamine tablet in healthy volunteers.
Efficacy and safety of ketamine in refractory status epilepticus in children. [2022]To evaluate the efficacy and safety of ketamine (KE) in the management of refractory convulsive status epilepticus (RSE) in children.
Influence of formulation and route of administration on ketamine's safety and tolerability: systematic review. [2021]Ketamine has rapid-onset antidepressant effects in patients with treatment-resistant depression. Common side effects include dissociation (a sense of detachment from reality) and increases in systolic and diastolic blood pressure. The objective of this structured review was to examine the effect of ketamine formulation and route of administration on its pharmacokinetics, safety and tolerability, to identify formulation characteristics and routes of administration that might minimise side effects.
The Ketamine Side Effect Tool (KSET): A comprehensive measurement-based safety tool for ketamine treatment in psychiatry. [2023]On a background of the rapidly expanding clinical use of ketamine and esketamine for treatment of depression and other conditions, we examined safety monitoring, seeking to identify knowledge gaps relevant to clinical practice.
Ketamine Alters Hippocampal Cell Proliferation and Improves Learning in Mice after Traumatic Brain Injury. [2019]WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Traumatic brain injury induces cellular proliferation in the hippocampus, which generates new neurons and glial cells during recovery. This process is regulated by N-methyl-D-aspartate-type glutamate receptors, which are inhibited by ketamine. The authors hypothesized that ketamine treatment after traumatic brain injury would reduce hippocampal cell proliferation, leading to worse behavioral outcomes in mice.
Effects of an intravenous ketamine infusion on inflammatory cytokine levels in male and female Sprague-Dawley rats. [2022]Ketamine, a multimodal dissociative anesthetic drug, is widely used as an analgesic following traumatic injury. Although ketamine may produce anti-inflammatory effects when administered after injury, the immunomodulatory properties of intravenous (IV) ketamine in a non-inflammatory condition are unclear. In addition, most preclinical studies use an intraperitoneal (IP) injection of ketamine, which limits its clinical translation as patients usually receive an IV ketamine infusion after injury.
Effects of a Subanesthetic Ketamine Infusion on Inflammatory and Behavioral Outcomes after Closed Head Injury in Rats. [2023]Traumatic brain injury (TBI) affects millions of people annually, and most cases are classified as mild TBI (mTBI). Ketamine is a potent trauma analgesic and anesthetic with anti-inflammatory properties. However, ketamine's effects on post-mTBI outcomes are not well characterized. For the current study, we used the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA), which replicates the biomechanics of a closed-head impact with resulting free head movement. Adult male Sprague-Dawley rats sustained a single-session, repeated-impacts CHIMERA injury. An hour after the injury, rats received an intravenous ketamine infusion (0, 10, or 20 mg/kg, 2 h period), during which locomotor activity was monitored. Catheter blood samples were collected at 1, 3, 5, and 24 h after the CHIMERA injury for plasma cytokine assays. Behavioral assays were conducted on post-injury days (PID) 1 to 4 and included rotarod, locomotor activity, acoustic startle reflex (ASR), and pre-pulse inhibition (PPI). Brain tissue samples were collected at PID 4 and processed for GFAP (astrocytes), Iba-1 (microglia), and silver staining (axonal injury). Ketamine dose-dependently altered locomotor activity during the infusion and reduced KC/GRO, TNF-α, and IL-1β levels after the infusion. CHIMERA produced a delayed deficit in rotarod performance (PID 3) and significant axonal damage in the optic tract (PID 4), without significant changes in other behavioral or histological measures. Notably, subanesthetic doses of intravenous ketamine infusion after mTBI did not produce adverse effects on behavioral outcomes in PID 1-4 or neuroinflammation on PID 4. A further study is warranted to thoroughly investigate beneficial effects of IV ketamine on mTBI given multi-modal properties of ketamine in traumatic injury and stress.