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

Drug Resistant Epilepsy Clinical Trial

Official title:

A Pilot Study to Assess the Efficacy of Subanesthetic Doses of IV Ketamine in the Treatment Drug Resistant Epilepsy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05019885
• Other study ID #: STUDY-20-01911
• Status: Recruiting
• Phase: Phase 2
• Start date: August 26, 2022
• Est. completion date: July 2024

Study information

• Verified date: September 2023
• Source: Icahn School of Medicine at Mount Sinai
• Contact: Onome Eka, MBBS MPH
• Phone: 212-241-8861
• Email: onome.eka[@]mssm.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 6
• Est. completion date: July 2024
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.)

Related Conditions & MeSH terms

• Drug Resistant Epilepsy
• Epilepsy
• Refractory Epilepsy

Intervention

Drug:
• Ketamine Hydrochloride
Three times a week (M, W, F) for 2 consecutive weeks.

Locations

Country	Name	City	State
United States	Mount Sinai Hospital	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Madeline Fields

Country where clinical trial is conducted

United States, 

References & Publications (37)

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* Note: There are 37 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with seizure reduction	50% seizure reduction during the 2 week period of active treatment	2 week during active treatment
Primary	Number of participants with seizure reduction	50% seizure reduction during the 28 days post-infusion.	28 days post infusion
Primary	Seizure frequency	Return to pre-ketamine infusion seizure frequency in 3 months	3 months post infusion
Secondary	Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) Score	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.	Week 6
Secondary	Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) Score	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.	Week 10
Secondary	Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) Score	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.	Week 14
Secondary	Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) Score	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.	Week 18
Secondary	Quality of Life in Epilepsy (QOLIE-10)	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.	Week 6
Secondary	Quality of Life in Epilepsy (QOLIE-10)	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.	Week 10
Secondary	Quality of Life in Epilepsy (QOLIE-10)	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.	Week 14
Secondary	Quality of Life in Epilepsy (QOLIE-10)	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.	Week 18
Secondary	General Anxiety Disorder 7-item questionnaire (GAD-7)	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.	week 6
Secondary	General Anxiety Disorder 7-item questionnaire (GAD-7)	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.	week 10
Secondary	General Anxiety Disorder 7-item questionnaire (GAD-7)	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.	week 14
Secondary	General Anxiety Disorder 7-item questionnaire (GAD-7)	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.	week 18