Safety and Efficacy of Butylphthalide Soft Capsules for Cognitive Impairment Comorbid With Focal Epilepsy in Elderly Patients: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 220
- 试验地点
- 1
- 主要终点
- Change in Montreal Cognitive Assessment (MoCA) Total Score from Baseline to 48 Weeks
研究概览
简要总结
This is a multicenter, randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of butylphthalide soft capsules for treating cognitive impairment in elderly patients with focal epilepsy.
Study Population: 220 elderly patients (60-85 years) with focal epilepsy and mild to moderate cognitive impairment (Montreal Cognitive Assessment score 18-25).
Intervention: Participants will be randomly assigned 1:1 to receive either butylphthalide soft capsules (0.2g three times daily) or matching placebo for 48 weeks, while continuing their stable anti-seizure medication regimen.
Primary Outcome: Change in Montreal Cognitive Assessment (MoCA) total score from baseline to 48 weeks.
Secondary Outcomes: Changes in neuropsychological tests (Trail Making Test, Digit Span, Rey Auditory Verbal Learning Test), seizure control measures, functional status (Activities of Daily Living, Quality of Life in Epilepsy), and exploratory neurobiological markers.
This study addresses an important unmet medical need, as current epilepsy treatments focus primarily on seizure control but lack effective interventions for epilepsy-associated cognitive impairment. Butylphthalide, a neuroprotective agent approved for acute ischemic stroke in China, has shown promise in other cognitive disorders and may benefit this patient population through its multiple neuroprotective mechanisms.
详细描述
Background and Rationale:
Epilepsy affects approximately 9 million people in China, with focal epilepsy comprising 60-70% of adult cases. Cognitive impairment occurs in 40-60% of elderly patients with focal epilepsy, significantly impacting quality of life and daily functioning. Current anti-seizure medications effectively control seizures in ~70% of patients but provide limited benefit for cognitive symptoms, and some may even worsen cognitive function.
Butylphthalide (DL-3-n-butylphthalide) is a multi-target neuroprotective compound originally derived from celery seeds, approved in China for acute ischemic stroke treatment. Its mechanisms include improving cerebral microcirculation, protecting mitochondrial function, reducing oxidative stress, anti-inflammatory effects, and anti-apoptotic properties. Previous studies have demonstrated efficacy in vascular cognitive impairment and mild cognitive impairment, but its effects in epilepsy-associated cognitive dysfunction remain unexplored.
Study Design:
This investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial will enroll 220 participants across 5 centers in China. The study represents off-label use of butylphthalide for cognitive impairment comorbid with epilepsy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double-blind design where participants, care providers, investigators, and outcomes assessors are masked to treatment assignment. Emergency unblinding procedures are available when medically necessary.
入排标准
- 年龄范围
- 60 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 60-85 years (inclusive)
- •Diagnosed with focal epilepsy according to ILAE 2025 latest classification standards, with disease duration ≥2 years
- •Currently receiving stable anti-seizure medication (ASM) treatment for ≥3 months, with good seizure control (monthly seizure frequency ≤4 times in the past 3 months)
- •Cognitive impairment: Montreal Cognitive Assessment (MoCA) score 18-25 points (inclusive)
- •Basic Chinese language comprehension and expression ability, able to cooperate with neuropsychological testing
- •Voluntary participation and signed informed consent
排除标准
- •Diagnosed with various types of dementia (including Alzheimer's disease, vascular dementia, etc.)
- •Clear history of stroke with corresponding lesions on neuroimaging, or severe white matter lesions on brain MRI
- •Other neurological diseases that may cause cognitive impairment (traumatic brain injury, encephalitis, hydrocephalus, etc.)
- •Systemic diseases that may cause cognitive impairment (severe cardiac, hepatic, renal dysfunction, endocrine diseases, etc.)
- •Current severe depression or other psychiatric diseases affecting cognitive assessment
- •History of alcohol dependence, drug abuse, or other substance use affecting cognitive function
- •Allergy to butylphthalide or its excipients
- •Participation in other drug clinical trials within 30 days
- •Other conditions deemed inappropriate for participation by investigators
研究组 & 干预措施
Butylphthalide Group
Participants receive butylphthalide soft capsules 0.2g (two 0.1g capsules) orally three times daily before meals for 48 weeks, while continuing their stable anti-seizure medication regimen.
干预措施: Butylphthalide (Drug)
Placebo Group
Participants receive matching placebo capsules orally three times daily before meals for 48 weeks, while continuing their stable anti-seizure medication regimen. Placebo capsules are identical in appearance, weight, and odor to butylphthalide capsules.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Montreal Cognitive Assessment (MoCA) Total Score from Baseline to 48 Weeks
时间窗: Baseline and 48 weeks
The Montreal Cognitive Assessment (MoCA) is a validated cognitive screening tool that evaluates multiple cognitive domains including visuospatial/executive function, naming, memory, attention, language, abstraction, delayed recall, and orientation. The total score ranges from 0 to 30 points, with higher scores indicating better cognitive function. The primary outcome is the change in MoCA total score from baseline to 48 weeks, calculated as: (MoCA score at 48 weeks) - (MoCA score at baseline). A positive change indicates cognitive improvement, while a negative change indicates cognitive decline.
次要结局
- Trail Making Test Part B (TMT-B) Completion Time Changes(Baseline, 12 weeks, 24 weeks, 36 weeks, and 48 weeks)
- Digit Span Forward Test Score Changes(Baseline, 12 weeks, 24 weeks, 36 weeks, and 48 weeks)
- Rey Auditory Verbal Learning Test (RAVLT) Immediate Recall Score Changes(Baseline, 12 weeks, 24 weeks, 36 weeks, and 48 weeks)
- Average Monthly Seizure Frequency Percentage Change(Baseline, 12 weeks, 24 weeks, 36 weeks, and 48)
- Proportion of Participants with ≥50% Reduction in Seizure Frequency(Baseline and 48 weeks)
- Activities of Daily Living (ADL) Scale Score Changes(Baseline, 12 weeks, 24 weeks, 36 weeks, and 48 weeks)
- Quality of Life in Epilepsy Inventory-31-Patient weighted (QOLIE-31-P) Score Changes(Baseline, 12 weeks, 24 weeks, 36 weeks, and 48 weeks)
- Number of Participants with Treatment-Related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0)(12 weeks, 24 weeks, 36 weeks, and 48 weeks)
- Number of Participants with Serious Adverse Events(12 weeks, 24 weeks, 36 weeks, and 48 weeks)
- Number of Participants with Clinically Significant Hepatic Function Abnormalities(24 weeks and 48 weeks)
- Number of Participants with Clinically Significant Renal Function Abnormalities(24 weeks and 48 weeks)
- Digit Span Backward Test Score Changes(Baseline, 12 weeks, 24 weeks, 36 weeks, and 48 weeks)
- Rey Auditory Verbal Learning Test (RAVLT) Delayed Recall Score Changes(Baseline, 12 weeks, 24 weeks, 36 weeks, and 48 weeks)
- Number of Participants with Clinically Significant Hematological Abnormalities(24 weeks and 48 weeks)
- Trail Making Test Part A (TMT-A) Completion Time Changes(Baseline, 12 weeks, 24 weeks, 36 weeks, and 48 weeks)