What side effects are associated with this type of intervention?

Common treatments for epilepsy that involve NMDA receptor antagonism, such as subanesthetic ketamine, can have several side effects. Ketamine may cause disorientation, restlessness, dissociation, dizziness, delirium, psychosis, nausea, vomiting, and increased blood pressure. Other similar treatments like valproate and phenobarbital can lead to long-term memory deficits and severe cutaneous hypersensitivity. These side effects should be carefully considered when choosing an appropriate treatment plan.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of epilepsy, including those that act on NMDA receptors. One notable example is felbamate, which has NMDA receptor antagonistic properties. Additionally, the antiobesity drug fenfluramine, recently approved for Dravet syndrome, may control seizures through modulation of NMDA receptors. These treatments share a similar mechanism to subanesthetic ketamine, which is currently being studied for its efficacy in treating drug-resistant epilepsy through NMDA receptor antagonism.

What other types of research exist?

Promising novel alternatives to subanesthetic ketamine for epilepsy patients include: 1) KA-104, a multitargeted anticonvulsant with potent antinociceptive activity, showing favorable in vitro ADME-Tox properties. 2) Lamotrigine, which is used as an alternative option for patients whose symptoms do not improve with first-line therapies. 3) Gabapentin and pregabalin, which have shown efficacy in managing neuropathic pain and may offer benefits for epilepsy management. 4) Dexmedetomidine, which has been studied in combination with intravenous anesthetics for its potential benefits in electroconvulsive therapy and may have applications in epilepsy treatment.

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NMDA Receptor Antagonist

IV Ketamine for Epilepsy

Q: What is the mechanism of action of this treatment?

Common treatments for epilepsy work through various mechanisms to stabilize neuronal activity and prevent seizures. Sodium channel blockers, such as carbamazepine and phenytoin, inhibit repetitive firing of neurons by stabilizing the inactive state of sodium channels. GABA enhancers, like benzodiazepines and barbiturates, increase the inhibitory effects of GABA neurotransmission, reducing neuronal excitability. NMDA receptor antagonists, such as ketamine, inhibit excitatory neurotransmission by blocking NMDA receptors, which are involved in synaptic plasticity and excitatory signaling. Understanding these mechanisms is crucial for epilepsy patients as it helps tailor treatments to individual needs, manage side effects, and explore new therapeutic options like subanesthetic ketamine, which may offer benefits for drug-resistant epilepsy.

Phase 2

Recruiting

Led By Madeline Fields, MD

Research Sponsored by Madeline Fields

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Established diagnosis of Drug Resistant Epilepsy (DRE) i.e. failed two or more appropriately chosen anti-seizure medications (ASMs)

Adults (18 years or older)

Must not have

Patients that are immobile i.e. wheel chair bound, bed ridden individuals

Patients <18 years of age

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 3 months post infusion

Awards & highlights

Approved for 5 Other Conditions

All Individual Drugs Already Approved

No Placebo-Only Group

Summary

This trial is testing small doses of ketamine to help people with epilepsy who don't respond to regular medications. Ketamine can help calm the brain and reduce seizures. The study will monitor patients' seizure activity and mood over time. Ketamine has been used in various settings for its ability to reduce seizures.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While not specified here, common side effects of subanesthetic ketamine may include confusion, hallucinations, changes in blood pressure and heart rate, dizziness and nausea. Long-term effects are unclear since it's usually used short-term.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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I am 18 years old or older.

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I experience more than 4 seizures of any type per month.

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My epilepsy device settings have been stable for at least 4 weeks.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I am under 18 years old.

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I have a heart condition.

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I have a history of aneurysm, aortic dissection, arteriovenous malformation, or brain bleed.

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I am taking medications for my mental health, such as amphetamines or MAO inhibitors.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 3 months post infusion

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~3 months post infusion

This trial's timeline: 3 weeks for screening, Varies for treatment, and 3 months post infusion for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of participants with seizure reduction

Seizure frequency

Secondary study objectives

General Anxiety Disorder 7-item questionnaire (GAD-7)

Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) Score

Quality of Life in Epilepsy (QOLIE-10)

Side effects data

From 2020 Phase 4 trial • 75 Patients • NCT03156504

Lightheadedness with low blood pressure

Pump Malfunction

PTSD

100%

80%

60%

40%

20%

Study treatment Arm

Ketamine

Awards & Highlights

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: IV Ketamine HydrochlorideExperimental Treatment1 Intervention

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ketamine

FDA approved

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for epilepsy work through various mechanisms to stabilize neuronal activity and prevent seizures. Sodium channel blockers, such as carbamazepine and phenytoin, inhibit repetitive firing of neurons by stabilizing the inactive state of sodium channels. GABA enhancers, like benzodiazepines and barbiturates, increase the inhibitory effects of GABA neurotransmission, reducing neuronal excitability. NMDA receptor antagonists, such as ketamine, inhibit excitatory neurotransmission by blocking NMDA receptors, which are involved in synaptic plasticity and excitatory signaling. Understanding these mechanisms is crucial for epilepsy patients as it helps tailor treatments to individual needs, manage side effects, and explore new therapeutic options like subanesthetic ketamine, which may offer benefits for drug-resistant epilepsy.