Ketamine for Stroke

(QUEST-KETA Trial)

Overseen By Sudhir Aggarwal, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Lower Merion Neurology Research Foundation

Disqualifiers: Pregnancy, Psychiatric illness, Hypertension, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether ketamine, administered through an IV, can protect the brain in individuals who have recently experienced an ischemic stroke (a stroke caused by a blocked blood vessel in the brain). The researchers aim to determine if ketamine can reduce brain damage by safeguarding nerve cells. Participants will receive either ketamine or a placebo (a substance with no active drug) to compare outcomes. Individuals who have had an ischemic stroke within the last 24 hours and have MRI evidence of this may be suitable for the trial. As a Phase 2, Phase 3 trial, this study measures ketamine's effectiveness in an initial group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking stroke treatment.

Do I need to stop my current medications for the trial?

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that ketamine is generally safe for short-term use in people. Studies have found it particularly safe for treating depression that doesn't respond to other treatments, suggesting it might also be safe for conditions like stroke.

In one study on brain injuries and stroke, ketamine reduced harmful brain activity, indicating its safety and effectiveness. Another study found that ketamine helped prevent further brain damage after a stroke, suggesting it could protect the brain.

Overall, ketamine appears well-tolerated, with no major safety issues reported in other uses. This is encouraging for those considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for stroke?

Unlike the standard treatments for stroke, which often include clot-busting drugs and therapies aimed at restoring blood flow, ketamine offers a unique approach by potentially protecting brain cells from damage. Ketamine is thought to act on the NMDA receptors, which could help reduce excitotoxicity, a harmful process that occurs after a stroke. Researchers are excited about ketamine because it could not only limit damage but also improve recovery outcomes, offering a new hope for faster and more effective stroke recovery.

What evidence suggests that ketamine might be an effective treatment for stroke?

Research shows that ketamine, which participants in this trial may receive, might help protect the brain after a stroke. Studies have found that ketamine can slow the spread of brain damage in stroke patients and reduce harmful brain activity that could cause further harm. Animal studies indicate that ketamine may help prevent brain injury and improve behavior after a stroke. These findings suggest that ketamine could be a promising treatment for protecting the brain in stroke patients. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with acute ischemic stroke within the last 24 hours, confirmed by MRI. They must have been relatively independent before the stroke (modified Rankin scale of 0-2) and agree to participate. It's not for those with brain hemorrhage, pregnancy, known ketamine allergy, eligibility for certain other stroke treatments, psychiatric illness, seizure at symptom onset or severe uncontrolled high blood pressure.

Inclusion Criteria

I am 18 or older and had a stroke within the last 24 hours.

There is evidence of a recent stroke on the MRI scan.

I was independent in daily activities before my stroke.

Exclusion Criteria

I needed help with my daily activities before my stroke.

You have a mental illness already.

You had a bad reaction to ketamine before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive Ketamine or placebo infusion for 24 hours with Midazolam to prevent psychogenic effects

1 day

Inpatient stay on telemetry floor

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments on day 1, day 4, and at 90 days

90 days

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine
• Midazolam injection
• Normal Saline

Trial Overview The study tests if intravenous ketamine can protect the brain after an acute ischemic stroke by reducing harmful overactivity of nerve cells. Participants will receive either ketamine or placebo (normal saline), and some may get a sedative (midazolam injection) as part of this phase II trial.

How Is the Trial Designed?

Group I: Study Drug Experimental Treatment 2 Interventions

Will receive Ketamine infusion, and Midazolam (Versed).

Group II: Placebo Placebo Group 2 Interventions

Will receive Normal saline infusion and Midazolam (Versed).

Ketamine is already approved in 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

Who Is Running the Clinical Trial?

Lower Merion Neurology Research Foundation

Lead Sponsor

Trials

1

Recruited

120+

Published Research Related to This Trial

An extended release oral ketamine tablet was found to be safe and well tolerated in a study of seven patients with treatment-resistant depression/anxiety, with no significant changes in vital signs and only one brief report of dissociation.

All patients experienced over 50% improvements in mood ratings over 96 hours, suggesting that while the onset of mood improvement is slightly delayed compared to injectable forms, this oral formulation could be a promising option for treating resistant depression and anxiety disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of extended release ketamine tablets in patients with treatment-resistant depression and anxiety: open label pilot study. Glue, P., Medlicott, NJ., Neehoff, S., et al.[2022]

A review of 41 treatment arms from 21 studies found that ketamine formulations that maximize first pass metabolism and delay the time to peak concentration (Tmax) are associated with better safety and tolerability, particularly in reducing side effects like dissociation and increased blood pressure.

The study revealed strong correlations between the ketamine:norketamine ratio and both dissociation ratings and blood pressure changes, suggesting that careful formulation can help minimize adverse effects while maintaining the antidepressant efficacy of ketamine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of formulation and route of administration on ketamine's safety and tolerability: systematic review. Glue, P., Russell, B., Medlicott, NJ.[2021]

A Phase I study involving 32 patients showed that esketamine (0.5 mg/kg) is generally safe and well-tolerated for use in painless gastroscopy, with no serious adverse events reported.

Esketamine resulted in a shorter recovery time compared to racemic ketamine (9 minutes vs. 13 minutes), making it a potentially more efficient option for anesthesia without gender differences affecting its pharmacokinetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Safety of Esketamine in Chinese Patients Undergoing Painless Gastroscopy in Comparison with Ketamine: A Randomized, Open-Label Clinical Study. Wang, J., Huang, J., Yang, S., et al.[2022]

Intravenous ketamine has been shown to be effective in treating refractory convulsive status epilepticus (RCSE) in children, resolving 14 out of 19 episodes in a study involving 13 patients aged 2 months to 11 years.

Ketamine offers a significant advantage by potentially avoiding endotracheal intubation, which can worsen the prognosis of RCSE, as it was used successfully in 5 patients as an alternative to conventional anesthetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine in refractory convulsive status epilepticus in children avoids endotracheal intubation. Ilvento, L., Rosati, A., Marini, C., et al.[2018]

In a study of 9016 patients receiving ketamine intravenous therapy (KIT) for depression, 53.6% showed a significant response (≥50% reduction in depression scores) within 14-31 days, indicating KIT's efficacy in real-world settings.

While most patients benefited from KIT, a small percentage (8.4%) experienced worsening depressive symptoms, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective analysis of ketamine intravenous therapy for depression in real-world care settings. McInnes, LA., Qian, JJ., Gargeya, RS., et al.[2023]

In a European clinical trial, a 55-year-old male with treatment-resistant depression and substance use disorder showed significant improvement in depression symptoms after a single intravenous infusion of ketamine, with reductions in Hamilton Depression Rating Scale (HDRS) scores from 36 to 16 and Beck Depression Inventory (BDI) scores from 26 to 9.

The antidepressant effects of ketamine were rapid, with the patient reporting improvements just 25 minutes into the infusion, and these effects lasted for at least 7 days, demonstrating ketamine's potential as a fast-acting treatment for depression even in patients with co-occurring substance use disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous ketamine therapy in a patient with a treatment-resistant major depression. Liebrenz, M., Borgeat, A., Leisinger, R., et al.[2022]

Oral ketamine has shown effectiveness in treating severe depression, including treatment-resistant cases and those with suicidal ideation, based on various studies including randomized controlled trials with doses ranging from 0.25 to 7 mg/kg.

Despite its lower bioavailability (20%-25% reaching the bloodstream), oral ketamine is well tolerated and can be adjusted for individual needs, making it a practical option for depression treatment alongside conventional antidepressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Ketamine for Depression, 1: Pharmacologic Considerations and Clinical Evidence. Andrade, C.[2019]

Ketamine and esketamine are effective for rapidly alleviating symptoms of treatment-resistant depression, with esketamine being approved for use in the US and EU, while ketamine is often used off-label.

Both treatments may require repeated doses and the addition of standard antidepressants to sustain their effects, but they also carry risks of adverse effects and potential for abuse, highlighting the need for further research on their long-term safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy: Ketamine and Esketamine. Feeney, A., Papakostas, GI.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02258204?term=AREA%5BConditionSearch%5D(%22Cerebrovascular%20Disease%22)%20AND%20AREA%5BInterventionSearch%5D(%22Anesthetics%22)&rank=6

Ketamine for Thrombolysis in Acute Ischemic Stroke Study outcomes - The primary efficacy outcome is cerebral infarction growth on diffusion weighted imaging between admission and day 1. The primary safety ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9419113/

Ketamine and Its Emergence in the Field of Neurology - PMC Hertle et al. [28] showed that ketamine was associated with a decrease in CSD incidence in TBI, SAH, and malignant hemispheric stroke.

3. nature.com nature.com/articles/s41598-024-59835-5

Ketamine-induced prevention of SD-associated late infarct ... Ketamine treatment caused a lesser pronounced hypoemic response and prevented infarct growth in the delayed phase after experimental ischemia.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0091305720300940

Neuronal brain injury after cerebral ischemic stroke is ... These findings suggest that (R)-ketamine can protect against neuronal injury and behavioral abnormalities in mice after MCAO. Therefore, it is likely that (R)- ...

5. withpower.com withpower.com/trial/phase-2-and-3-ischemic-stroke-2020-2380d

Ketamine for Stroke · Info for Participants Research suggests that (R)-ketamine can protect against brain injury and improve behavior in mice after a stroke, indicating potential as a treatment for ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8002231/

Somatic Comorbidities and Cardiovascular Safety in Ketamine ... This study supports evidence for good safety and tolerability profile for short-term IV ketamine use in TRD treatment.