Randomized Double-blind Placebo-controlled Trial of Memantine Hydrochloride for the Treatment of Childhood-onset Epileptic Encephalopathies
Overview
- Phase
- Phase 4
- Intervention
- Memantine Hydrochloride 10 mg
- Conditions
- Epileptic Encephalopathy, Childhood-Onset
- Sponsor
- Kenneth Myers, MD
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Rate of Responder versus Non-Responder Status with Memantine
- Status
- Completed
- Last Updated
- 4 years ago
Overview
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.
Detailed Description
Memantine, a drug approved for Alzheimer's dementia, exerts its therapeutic effect through its action as a low to moderate affinity non-competitive (open channel) N-methyl-D-aspartate receptor (NMDA-R) antagonist, which binds preferentially to the NMDA receptor-operated cation channels. It blocks the effects of persistently elevated levels of glutamate that may lead to neuronal dysfunction. Memantine may also have anti-inflammatory effects. Memantine has been used off-label in children and adolescents with autism spectrum disorder, to improve the cognitive impairment. Epileptic encephalopathy, as well as other forms of epilepsy, may occur as a result of multiple etiologies, including genetic and inflammatory pathologies. Ion channels were long considered to be implicated in genetic epilepsy. Indeed one of the many possible causes of epilepsy is NMDA receptor dysfunction. In the present study, the investigators plan to investigate the potential benefit of memantine as a treatment for epileptic encephalopathy. A double-blind placebo-controlled cross-over design will be used, with participants receiving 6 weeks of memantine and 6 weeks of placebo, with a 2-week washout period in between.
Investigators
Kenneth Myers, MD
Assistant Professor (Clinical), Neurologist Pediatrician
McGill University Health Centre/Research Institute of the McGill University Health Centre
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
Memantine Hydrochloride 10 mg Placebo
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
Intervention: Memantine Hydrochloride 10 mg
Placebo Memantine Hydrochloride 10 mg
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
Intervention: Memantine Hydrochloride 10 mg
Outcomes
Primary Outcomes
Rate of Responder versus Non-Responder Status with Memantine
Time Frame: Week 6 or 14
"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.
Rate of Responder versus Non-Responder Status with Placebo
Time Frame: Week 6 or 14
"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.
Secondary Outcomes
- 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)
- Cognitive Function Change with Placebo(Week 6 or 14)
- Caregiver Impression of Change with Memantine(Week 6 or 14)
- Caregiver Impression of Change with Placebo(Week 6 or 14)
- Serum Inflammatory Markers Change with Memantine(Week 6 or 14)
- Serum Inflammatory Markers Change with Placebo(Week 6 or 14)