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The Efficacy of a Subanesthetic Doses of IV Ketamine in the Treatment Drug Resistant Epilepsy

Phase 2
Recruiting
Conditions
Drug Resistant Epilepsy
Medically Refractory Epilepsy
Refractory Epilepsy
Interventions
Registration Number
NCT05019885
Lead Sponsor
Madeline Fields
Brief Summary

Ketamine is a medication that came into clinical practice in the 1960's. Ketamine is used as an anesthetic and to provide pain relief. Recently, Ketamine was approved to treat drug resistant depression using subanesthetic doses. In the hospital setting, intravenous anesthetic dosages are used to treat unrelenting seizures known as status epilepticus in comatose patients. Ketamine in subanesthetic doses has not been tried as a treatment for medication resistant seizures in the outpatient setting. This study would like to examine the effectiveness of subanesthetic ketamine in outpatients who suffer from drug resistant epilepsy.

Detailed Description

This is an open label pilot study that will evaluate the effectiveness of a sub-anaesthetic dose (0.5mg/kg) of IV Ketamine in Drug Resistant Epilepsy Patients. Mood assessments will also be administered. The study consists of 3 phases:

Screening : Seizure diary will be prospectively filled for 4 weeks and subjects must have at least 4 seizures in 28 days to proceed to the treatment phase. Baseline mood assessment will be performed (NDDI-E, QOLIE-10, GAD 7 )

Treatment Phase: This phase will consist of 6 study visits (3 visits/ week for 2 weeks). Patients will receive 0.5mg/kg Racemic ketamine IV over 40 min three times a week (M, W, F) for 2 consecutive weeks.

Treatment Visit 1: Monday Week 5(baseline seizures diary collected) Treatment Visit 2: Wednesday Week 5 Treatment Visit 3: Friday Week 5 Treatment Visit 4: Monday Week 6 Treatment Visit 5: Wednesday Week 6 Treatment Visit 6: Friday Week 6 (Mood assessments performed prior to infusion)

Post- Treatment Phase : This phase will consist of 5 post infusion safety assessments and 3 post-treatment assessments.

Post-Infusion Safety Assessment 1: Saturday Week 6 (Adverse Event Assessment) Post-Infusion Safety Assessment 2: Sunday Week 7 (Adverse Event Assessment) Post-Infusion Safety Assessment 3: Monday Week 7 (Adverse Event Assessment) Post-Infusion Safety Assessment 4: Monday Week 8 (Adverse Event Assessment) Post-Infusion Safety Assessment 5: Monday Week 9 (Adverse Event Assessment)

Post-Treatment Assessment 1: phone call week 10 (Seizure diary collection, mood assessments performed) Post-Treatment Assessment 2: phone call week 14 (Seizure diary) Post-Treatment Assessment 3: phone call week 18 (Seizure diary collection, mood assessments performed)

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
9
Inclusion Criteria
  • Provision of signed and dated informed consent form
  • Adults (18 years or older)
  • Cognitively impaired adults are not excluded (i.e. will be included in the study)
  • Established diagnosis of Drug Resistant Epilepsy (DRE) i.e. failed two or more appropriately chosen anti-seizure medications (ASMs)
  • EEG consistent with focal or generalized epilepsy
  • Patients must have >4 focal aware, focal impaired aware, focal to bilateral tonic clonic or generalized tonic clonic seizures per month.
  • Patients can be on >/= 1 anti-seizure medication (ASM) at the time of enrollment on stable doses 12 weeks prior to initiation
  • Patients on Epilepsy devices: Vagal nerve stimulator (VNS), Deep brain stimulator (DBS) or Responsive Nerve Stimulator (RNS) must have remained stable for at least 4 weeks before the screening visit. Adjustment of devices is not allowed during the study.

Exclusion Criteria

  • Patients <18 years of age
  • Pregnant women
  • Women that are breast feeding
  • Patients who had >21 days of seizure freedom in the last year.
  • Patients with a history of status epilepticus within 3 months of screening
  • Patients with a history of alcoholism of drug misuse within the last 2 years
  • Unstable medical illness
  • Serious or imminent suicidal or homicidal risk
  • Patients with cardiovascular disease
  • Patients with schizophrenia
  • Patients with history of aneurysm or aortic dissection, arteriovenous malformation and intracerebral hemorrhage
  • Patients that are immobile i.e. wheel chair bound, bed ridden individuals
  • Patients on psychostimulants (amphetamines, methylphenidate etc.) and Monoamine oxidase inhibitors (selegiline, isocarboxazid, phenelzine etc.)
Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
IV Ketamine HydrochlorideKetamine Hydrochloridedose 0.5mg/kg of IV Ketamine Hydrochloride over 40 min
Primary Outcome Measures
NameTimeMethod
Seizure frequency3 months post infusion

Return to pre-ketamine infusion seizure frequency in 3 months

Number of participants with seizure reduction28 days post infusion

50% seizure reduction during the 28 days post-infusion.

Secondary Outcome Measures
NameTimeMethod
Quality of Life in Epilepsy (QOLIE-10)Week 18

Quality of Life in Epilepsy (QOLIE)-10 scale is a validated, reliable instrument measuring quality of life on a scale from 10-51, lower score indicates better health outcome.

General Anxiety Disorder 7-item questionnaire (GAD-7)week 18

The General Anxiety Disorder 7-item questionnaire (GAD-7) is a 7-item questionnaire that asks user to rank how often they have been bothered by seven problems over the past two weeks from "0" (not at all) to "3" (nearly every day). The items that users are asked to rank levels of nervousness, anxiousness, relaxing, restlessness, irritability and fearfulness. Full scale from 0-21, with higher score indicating more symptoms.

Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) ScoreWeek 18

The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) is a 6-item questionnaire validated to screen for depression in people with epilepsy. Scores range from 6 - 24, with higher scores indicating more depressive symptoms.

Trial Locations

Locations (1)

Mount Sinai Hospital

🇺🇸

New York, New York, United States

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