Randomized Double-blind Placebo-controlled Trial of Memantine Hydrochloride for the Treatment of Childhood-onset Epileptic Encephalopathies
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Rate of Responder versus Non-Responder Status with Memantine
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double-blinded Placebo vs Memantine
入排标准
- 年龄范围
- 6 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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
干预措施: Memantine Hydrochloride 10 mg (Drug)
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
干预措施: Memantine Hydrochloride 10 mg (Drug)
结局指标
主要结局
Rate of Responder versus Non-Responder Status with Memantine
时间窗: 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
时间窗: 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.
次要结局
- 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)
研究者
Kenneth Myers, MD
Assistant Professor (Clinical), Neurologist Pediatrician
McGill University Health Centre/Research Institute of the McGill University Health Centre