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

120 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if giving ketamine can help protect the brains of stroke patients by calming overactive nerve cells.

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.

What data supports the effectiveness of the drug ketamine for stroke?

Research suggests that (R)-ketamine can protect against brain injury and improve behavior in mice after a stroke, indicating potential as a treatment for ischemic stroke. ^{1 2 3 4 5}

Is ketamine generally safe for use in humans?

Ketamine is generally considered safe for use in humans, but common side effects include dissociation (feeling detached from reality) and increased blood pressure and heart rate. Different formulations and ways of taking ketamine can affect how often these side effects happen. ^{1 6 7 8 9}

How is the drug ketamine unique for treating stroke?

Ketamine is unique for treating stroke because it acts as a neuroprotective agent, potentially preserving brain cells after a stroke by blocking NMDA receptors, which are involved in brain damage during ischemia (lack of blood flow). This mechanism is different from standard stroke treatments, which typically focus on restoring blood flow or preventing blood clots. ^{1 3 10 11 12}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. New Zealand 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. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

A retrospective analysis of ketamine intravenous therapy for depression in real-world care settings. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

[Effect of ketamine on global cerebral ischemia]. [2019]

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

Neuronal brain injury after cerebral ischemic stroke is ameliorated after subsequent administration of (R)-ketamine, but not (S)-ketamine. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Intravenous ketamine therapy in a patient with a treatment-resistant major depression. [2022]

6. England 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. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Influence of formulation and route of administration on ketamine's safety and tolerability: systematic review. [2021]

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

Prehospital Use of Ketamine in Mountain Rescue: A Survey of Emergency Physicians of a Single-Center Alpine Helicopter-Based Emergency Service. [2021]

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

Ketamine in refractory convulsive status epilepticus in children avoids endotracheal intubation. [2018]

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

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

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

Pharmacotherapy: Ketamine and Esketamine. [2023]

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

High-dose S(+)-ketamine improves neurological outcome following incomplete cerebral ischemia in rats. [2013]