IV Ketamine for Epilepsy

Overseen By Onome Eka, MBBS MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Madeline Fields

Must be taking: Anti-seizure medications

Must not be taking: Psychostimulants, MAO inhibitors

Disqualifiers: Pregnancy, Cardiovascular disease, Schizophrenia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 11

Duration: 2 weeks

8 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether low doses of ketamine, administered through an IV, can aid individuals with drug-resistant epilepsy. The goal is to determine if ketamine can reduce seizures in those unresponsive to other treatments. It targets adults who experience more than four seizures a month despite trying at least two anti-seizure medications. Individuals with stable epilepsy devices, such as VNS (a nerve stimulator), are also eligible. The study seeks new ways to manage difficult-to-treat epilepsy in everyday settings. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

You can continue taking your current anti-seizure medications as long as the doses have been stable for 12 weeks before starting the trial. However, if you are on psychostimulants or certain antidepressants (Monoamine oxidase inhibitors), you will need to stop those.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that ketamine is generally safe and well-tolerated for medical use. Studies have found that ketamine can effectively control seizures in patients. Specifically, one study revealed that 60.5% of patients stopped having seizures permanently after receiving ketamine treatment.

Ketamine is already approved for other uses. It has been safely used as an anesthetic since the 1960s and more recently for treating depression. With a wide margin of safety, it is usually safe even at higher doses. However, like many treatments, side effects can occur, so monitoring is important.

Overall, existing research suggests that ketamine could be a safe option for treating seizures, though individual experiences may vary. ^{1 2 3 4 5}

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

Most treatments for epilepsy, like antiepileptic drugs (AEDs), work by stabilizing electrical activity in the brain. But ketamine hydrochloride is different. It works by blocking NMDA receptors, which are involved in sending signals in the brain. This unique action might help control seizures in a new way. Researchers are excited because ketamine can be administered intravenously and may work quickly, offering potential relief for patients who haven't responded well to traditional medications.

What evidence suggests that this treatment might be an effective treatment for epilepsy?

A study of 58 patients with long-lasting seizures unresponsive to medication found that intravenous ketamine stopped seizures in 57% of cases. Another study demonstrated that ketamine could halt seizures by calming brain activity, offering promise for people with epilepsy. However, in some instances, seizures returned after the treatment ended, despite ketamine's initial effectiveness. These findings suggest ketamine might benefit those with drug-resistant epilepsy, but results can vary. More research is needed to understand its full potential. Participants in this trial will receive a dose of 0.5 mg/kg of IV Ketamine Hydrochloride over 40 minutes to further evaluate its effectiveness. ^{1 2 3 6 7}

Who Is on the Research Team?

Madeline Fields, MD

Principal Investigator

Icahn School of Medicine

Lara Marcuse, MD

Principal Investigator

Icahn School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults with drug-resistant epilepsy, having more than four seizures per month. They must have a stable use of seizure devices and anti-seizure medications for specific periods before the study starts. Excluded are pregnant or breastfeeding women, those at risk of suicide or homicide, with unstable illnesses, under 18 years old, substance misuse history within two years, certain cardiovascular conditions, immobility issues or recent severe seizures.

Inclusion Criteria

My cognitive impairment does not exclude me from this study.

Provision of signed and dated informed consent form

My epilepsy hasn't improved after trying two different medications.

Exclusion Criteria

I have had a severe seizure lasting minutes to hours within the last 3 months.

I am unable to walk and use a wheelchair or stay in bed.

Unstable medical illness

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Seizure diary filled, baseline mood assessment

Treatment

Participants receive 0.5mg/kg Racemic ketamine IV over 40 min three times a week for 2 consecutive weeks

2 weeks

6 visits (in-person)

Post-Treatment

Post-infusion safety assessments and post-treatment assessments including seizure diary collection and mood assessments

14 weeks

5 safety assessments (in-person), 3 assessments (phone calls)

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine Hydrochloride

Trial Overview The trial tests if low doses of IV Ketamine can help control seizures in outpatients with epilepsy that doesn't respond to standard drugs. It's exploring whether this approach used in hospitals for continuous seizures can be effective when patients aren't hospitalized.

How Is the Trial Designed?

Group I: IV Ketamine Hydrochloride Experimental Treatment 1 Intervention

dose 0.5mg/kg of IV Ketamine Hydrochloride over 40 min

Ketamine Hydrochloride is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Ketalar for:

• Anesthesia
• Pain management
• Depression
• Suicidal ideation

Approved in European Union as Ketamine Hydrochloride for:

• Anesthesia
• Pain management
• Treatment-resistant depression

Approved in Canada as Ketamine Hydrochloride for:

• Anesthesia
• Pain management
• Depression

Who Is Running the Clinical Trial?

Madeline Fields

Lead Sponsor

Trials

1

Recruited

9+

Published Research Related to This Trial

Low-dose intravenous ketamine can be effectively used in patients with drug-resistant epilepsy to manage seizures without causing oversedation, as demonstrated in a clinical case where it helped avoid intubation.

The study highlights the potential for transitioning from IV ketamine to an oral formulation, which may reduce hospital stay duration and suggests the need for personalized dosing based on pharmacogenomic factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine in seizure management and future pharmacogenomic considerations. Borsato, GS., Siegel, JL., Rose, MQ., et al.[2021]

In a study of 58 patients with refractory status epilepticus (RSE), intravenous ketamine achieved permanent control of seizures in 57% of episodes, indicating its potential efficacy as a treatment option.

The mortality rate was significantly lower (16%) when RSE was controlled within 24 hours of starting ketamine, suggesting that timely intervention with ketamine may improve outcomes in patients with RSE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous ketamine for the treatment of refractory status epilepticus: a retrospective multicenter study. Gaspard, N., Foreman, B., Judd, LM., et al.[2022]

Intranasal midazolam (INM) was effective for sedation in 24 out of 26 children, but intravenous ketamine and midazolam (IVKM) provided quicker sedation onset by an average of 5.3 minutes, making it a more efficient option for emergency procedures.

Children receiving INM were discharged 19 minutes earlier than those receiving IVKM, but overall sedation scores were significantly better with IVKM, indicating it offers a more consistent and satisfactory sedation experience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous ketamine plus midazolam is superior to intranasal midazolam for emergency paediatric procedural sedation. Acworth, JP., Purdie, D., Clark, RC.[2019]

In a study of 171 hospitalized patients receiving low-dose ketamine for pain management, 29.2% experienced neuropsychiatric adverse effects, with 15.2% needing to discontinue treatment due to these effects.

The study found no significant differences in the likelihood of experiencing adverse effects between patients who tolerated ketamine and those who did not, suggesting that predicting these effects is challenging; further research is needed to explore the potential role of benzodiazepines in mitigating these adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk Factors for the Development of Neuropsychiatric Adverse Effects in Ketamine-Treated Pain. Quirk, K., Smith, MA.[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]

Ketamine hydrochloride (50mg/ml) remains chemically stable for up to 180 days when stored in polypropylene syringes at room temperature, making it suitable for advance preparation.

The study confirmed that the concentration of ketamine does not fall below 90% of its initial value during this period, ensuring its efficacy for use as an anesthetic agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term stability of ketamine hydrochloride 50mg/ml injection in 3ml syringes. Huvelle, S., Godet, M., Hecq, JD., et al.[2022]

Intravenous ketamine dosing for procedural sedation in children varies by age, with recommended single bolus doses of 1.5 to 2.125 mg/kg, but larger doses can lead to deeper sedation and slower recovery times.

Using a smaller initial dose followed by a 'top-up' or continuous infusion can achieve the desired sedation level more effectively, with quicker recovery times, highlighting the importance of tailoring doses based on individual patient needs and the type of pain management required.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosing ketamine for pediatric procedural sedation in the emergency department. Dallimore, D., Herd, DW., Short, T., et al.[2022]

In a study involving 9 children with refractory convulsive status epilepticus (RSE), intravenous ketamine was found to be effective in resolving RSE in 6 of the patients, demonstrating its potential as a treatment option.

The treatment was deemed safe, as none of the patients experienced serious adverse events, suggesting that ketamine could be a viable alternative for children who do not respond to conventional anesthetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ketamine in refractory status epilepticus in children. Rosati, A., L'Erario, M., Ilvento, L., et al.[2022]

In a study involving mice, ketamine at a sub-effective dose did not enhance the pain-relieving (antinociceptive) effects of benzodiazepines like diazepam, chlordiazepoxide, and clonazepam, indicating a lack of interaction between these drugs.

Ketamine alone was effective in protecting against seizures induced by pentetrazole, but it did not change the anticonvulsant effects of the benzodiazepines, suggesting that combining these medications may not provide additional benefits in pain relief or seizure protection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of interaction between the behavioral effects of ketamine and benzodiazepines in mice. Fidecka, S., Pirogowicz, E.[2013]

In a study of 229 pediatric patients, intravenous (IV) ketamine administration led to a quicker discharge time from the emergency department compared to intramuscular (IM) ketamine, with a difference of 21 minutes from drug administration to discharge.

The overall rate of adverse events was lower in the IV group (20%) compared to the IM group (35%), suggesting that IV ketamine may have a better safety profile in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pediatric procedural sedation with ketamine: time to discharge after intramuscular versus intravenous administration. Ramaswamy, P., Babl, FE., Deasy, C., et al.[2022]

In a study involving nine children with medically intractable epilepsy, high-dose intravenous levetiracetam (IV-LEV) at doses averaging 228 mg/kg/day effectively resolved acute repetitive seizures in eight out of nine patients.

IV-LEV was well tolerated with no significant complications, and seven children experienced a reduction in seizure frequency, indicating its potential as a safe and effective treatment for acute seizure exacerbations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose intravenous levetiracetam for acute seizure exacerbation in children with intractable epilepsy. Depositario-Cabacar, DT., Peters, JM., Pong, AW., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11233303/

The efficacy and safety of ketamine in the treatment of super ... Ketamine use resulted in seizure cessation in 7 patients, but only 3 individuals (27%) achieved complete seizure cessation after discontinuing ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1876201824003393

Therapeutic potential of ketamine in management of epilepsy The results indicated that ketamine-treated patients experienced prolonged seizure durations, suggesting its utility in enhancing ECT efficacy.

3. sciencedirect.com sciencedirect.com/science/article/pii/S240584402400464X

Ketamine: Pro or antiepileptic agent? A systematic review Ketamine was successful in terminating the electro-clinical presentation of seizures. Burst suppression was noted in both cases. The article ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11586892/

Efficacy of Low‐Dose Ketamine and Propofol in the Treatment ... The study concluded that in the experimental RSE model, seizure control could be achieved with low‐dose combination of ketamine and propofol ...

5. withpower.com withpower.com/trial/phase-3-drug-resistant-epilepsy-9-2021-7d3f6

IV Ketamine for Epilepsy · Recruiting Participants for Phase ... In a study of 58 patients with refractory status epilepticus (RSE), intravenous ketamine achieved permanent control of seizures in 57% of episodes, indicating ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK470357/

Ketamine - StatPearls - NCBI Bookshelf - NIH An interprofessional team approach is necessary to improve patient outcomes related to ketamine and minimize adverse drug reactions.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/016812s040lbl.pdf

ketamine - accessdata.fda.gov Ketamine has a wide margin of safety; several instances of unintentional administration of overdoses of. KETALAR (up to ten times that usually required) have ...