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

Официальное название

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

Обзор

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.

Подробное описание

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)

Вмешательства

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

Первичные конечные точки

• Number of participants with seizure reduction [Срок оценки: 2 week during active treatment]
• Number of participants with seizure reduction [Срок оценки: 28 days post infusion]
• Seizure frequency [Срок оценки: 3 months post infusion]

Вторичные конечные точки (12)

• Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) Score [Срок оценки: Week 6]
• Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) Score [Срок оценки: Week 10]
• Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) Score [Срок оценки: Week 14]
• Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) Score [Срок оценки: Week 18]
• Quality of Life in Epilepsy (QOLIE-10) [Срок оценки: Week 6]
• Quality of Life in Epilepsy (QOLIE-10) [Срок оценки: Week 10]
• Quality of Life in Epilepsy (QOLIE-10) [Срок оценки: Week 14]
• Quality of Life in Epilepsy (QOLIE-10) [Срок оценки: Week 18]
• General Anxiety Disorder 7-item questionnaire (GAD-7) [Срок оценки: week 6]
• General Anxiety Disorder 7-item questionnaire (GAD-7) [Срок оценки: week 10]
• General Anxiety Disorder 7-item questionnaire (GAD-7) [Срок оценки: week 14]
• General Anxiety Disorder 7-item questionnaire (GAD-7) [Срок оценки: week 18]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Mount Sinai Hospital — New York

Публикации

• aan het Rot M, Collins KA, Murrough JW, Perez AM, Reich DL, Charney DS, Mathew SJ. Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression. Biol Psychiatry. 2010 Jan 15;67(2):139-45. doi: 10.1016/j.biopsych.2009.08.038. PMID 19897179
• Aram JA, Martin D, Tomczyk M, Zeman S, Millar J, Pohler G, Lodge D. Neocortical epileptogenesis in vitro: studies with N-methyl-D-aspartate, phencyclidine, sigma and dextromethorphan receptor ligands. J Pharmacol Exp Ther. 1989 Jan;248(1):320-8. PMID 2536430
• Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000 Feb 15;47(4):351-4. doi: 10.1016/s0006-3223(99)00230-9. PMID 10686270
• Brodie MJ. Road to refractory epilepsy: the Glasgow story. Epilepsia. 2013 May;54 Suppl 2:5-8. doi: 10.1111/epi.12175. PMID 23646962
• Dingledine R, Borges K, Bowie D, Traynelis SF. The glutamate receptor ion channels. Pharmacol Rev. 1999 Mar;51(1):7-61. No abstract available. PMID 10049997
• Esaian D, Joset D, Lazarovits C, Dugan PC, Fridman D. Ketamine continuous infusion for refractory status epilepticus in a patient with anticonvulsant hypersensitivity syndrome. Ann Pharmacother. 2013 Nov;47(11):1569-76. doi: 10.1177/1060028013505427. Epub 2013 Oct 9. PMID 24259603
• Feder A, Parides MK, Murrough JW, Perez AM, Morgan JE, Saxena S, Kirkwood K, Aan Het Rot M, Lapidus KA, Wan LB, Iosifescu D, Charney DS. Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial. JAMA Psychiatry. 2014 Jun;71(6):681-8. doi: 10.1001/jamapsychiatry.2014.62. PMID 24740528
• Fujikawa DG. Neuroprotective effect of ketamine administered after status epilepticus onset. Epilepsia. 1995 Feb;36(2):186-95. doi: 10.1111/j.1528-1157.1995.tb00979.x. PMID 7821277

Идентификаторы

NCT: NCT05019885 · STUDY-20-01911

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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