Memantine for Epileptic Encephalopathy

NCT03779672 | Completed Phase 4

• 1 other identifier: 22838
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the potential benefit of memantine hydrochloride as treatment for children with epileptic encephalopathy using a double-blind placebo-controlled cross-over design.

Conditions

Epileptic Encephalopathy, Childhood-Onset

Keywords

Memantine; N-methyl-D-aspartate receptor; Serum inflammatory; Seizure

Outcome Measures

Primary Outcomes (2)

• Rate of Responder versus Non-Responder Status with Memantine

  "Responder" defined as having ≥ 2 of (1) EEG improvement, (2) decreased seizure frequency, (3) cognitive improvement, (4) caregiver impression of improvement, (5) Serum Inflammatory Markers Change. These outcomes are individually defined in detail in the secondary outcomes below. Description of the primary variable(s) The primary efficacy endpoint is the composite cluster of the first occurrence, over the duration of study (randomization to study end date inclusive), of the EE improvement.

  Week 6 or 14

• Rate of Responder versus Non-Responder Status with Placebo

  "Responder" defined as having ≥ 2 of (1) EEG improvement, (2) decreased seizure frequency, (3) cognitive improvement, (4) caregiver impression of improvement, (5) Serum Inflammatory Markers Change. These outcomes are individually defined in detail in the secondary outcomes below. Description of the primary variable(s) The primary efficacy endpoint is the composite cluster of the first occurrence, over the duration of study (randomization to study end date inclusive), of the EE improvement.

  Week 6 or 14

Secondary Outcomes (10)

• EEG Change with Memantine

  Week 6 or 14

• EEG Change with Placebo

  Week 6 or 14

• Seizure Frequency Change with Memantine

  Week 6 or 14

• Seizure Frequency Change with Placebo

  Week 6 or 14

• Cognitive Function Change with Memantine

  Week 6 or 14

Other Outcomes (1)

• Adverse events

  Week 16

Study Arms (2)

Memantine Hydrochloride 10 mg Placebo

ACTIVE COMPARATOR

Blue colour capsules, for oral administration, containing 5 mg of active memantine or matching placebo for oral administration. Dose regimen: Memantine Hydrochloride * Week #1: 5 mg id (am), 1 caps * Week #2: 5 mg bid (am and pm), 2 caps * Weeks #3-6: 5 mg am \& 2x 5 mg pm, 3 caps Washout (Weeks #7-8) Placebo * Week #9: id (am), 1 caps * Week #10: bid (am and pm), 2 caps * Weeks #11-14: 1 caps am \& 2 caps pm, 3 caps

Drug: Memantine Hydrochloride 10 mg

Placebo Memantine Hydrochloride 10 mg

PLACEBO COMPARATOR

Placebo * Week #1: id (am), 1 caps * Week #2: bid (am and pm), 2 caps * Weeks #3-6: 1 caps am \& 2 caps pm, 3 caps Washout (Weeks #7-8) Memantine Hydrochloride * Week #9: 5 mg id (am), 1 caps * Week #10: 5 mg bid (am and pm), 2 caps * Weeks #11-14: 5 mg am \& 2x 5 mg pm, 3 caps

Drug: Memantine Hydrochloride 10 mg

Interventions

Memantine Hydrochloride 10 mg DRUG

* Week #1: 5 mg id (am), 1 caps * Week #2: 5 mg bid (am and pm), 2 caps * Weeks #3-6: 5 mg am \& 2x 5 mg pm, 3 caps * Weeks #7-8: Washout Placebo * Week #9: id (am), 1 caps * Week #10: bid (am and pm), 2 caps * Weeks #11-14: 1 caps am \& 2 caps pm, 3 caps OR Placebo * Week #1: id (am), 1 caps * Week #2: bid (am and pm), 2 caps * Weeks #3-6: 1 caps am \& 2 caps pm, 3 caps * Weeks #7-8: Washout Memantine * Week #9: 5 mg id (am), 1 caps * Week #10: 5 mg bid (am and pm), 2 caps * Weeks #11-14: 5 mg am \& 2x 5 mg pm, 3 caps

Also known as: PrSANDOZ MEMANTINE FCT10 mg Drug Identification Number (DIN) 02375532

Memantine Hydrochloride 10 mg Placebo; Placebo Memantine Hydrochloride 10 mg

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Written informed consent obtained
• Age 6-18 years (Weight ≥ 20 kg)
• Clinical diagnosis of epileptic encephalopathy
• Subject with epilepsy and developmental impairment;
• Epileptic activity itself contributes to severe cognitive and behavioural impairments
• Patients will typically have already have trialed at least two standard therapies
• Females of childbearing age:
• Negative urinary pregnancy test at screening
• Agree to use effective contraception for the duration of the study

You may not qualify if:

• Inability of a parent or legal guardian to give informed consent for any reason.
• Known hypersensitivity to memantine hydrochloride
• Taking concomitant Amantadine, Ketamine or Dextromethorphan, Cimetidine, Ranitidine, Procainamide, Quinidine, Quinine, Hydrochlorothiazide, Anticholinergics, L-dopa, Anticoagulant,
• Any degree of renal impairment

Sponsors & Collaborators

• Kenneth Myers, MD: lead

Study Sites (1)

Children Hospital - MUHC

Montreal, Quebec, H4A 3J1, Canada

Location

Related Publications (2)

• van den Munckhof B, de Vries EE, Braun KP, Boss HM, Willemsen MA, van Royen-Kerkhof A, de Jager W, Jansen FE. Serum inflammatory mediators correlate with disease activity in electrical status epilepticus in sleep (ESES) syndrome. Epilepsia. 2016 Feb;57(2):e45-50. doi: 10.1111/epi.13274. Epub 2015 Dec 14.

  PMID: 26666401 BACKGROUND

• Schiller K, Berrahmoune S, Dassi C, Corriveau I, Ayash TA, Osterman B, Poulin C, Shevell MI, Simard-Tremblay E, Sebire G, Myers KA. Randomized placebo-controlled crossover trial of memantine in children with epileptic encephalopathy. Brain. 2023 Mar 1;146(3):873-879. doi: 10.1093/brain/awac380.

  PMID: 36256600 DERIVED

MeSH Terms

Conditions

Seizures

Interventions

Memantine

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blinded Placebo vs Memantine
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor (Clinical), Neurologist Pediatrician

Model Details: Monocentric, Off-Label Use, Randomized, crossover, Double-blinded Placebo vs Memantine.

Study Record Dates

• First Submitted: December 5, 2018
• First Posted: December 19, 2018
• Study Start: February 7, 2019
• Primary Completion: November 8, 2021
• Study Completion: February 8, 2022
• Last Updated: March 11, 2022

Record last verified: 2022-03

Locations

CA (1)