Butylphthalide for Cognitive Impairment in Elderly Patients With Focal Epilepsy
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age60-85
SponsorFirst Affiliated Hospital of Wenzhou Medical University
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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)
Disqualifiers
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.)
Trial design
Design model
Parallel
Treatments tested in this trial
Butylphthalide
DrugButylphthalide soft capsules (0.1g per capsule) manufactured by CSPC NBP Pharmaceutical Co., Ltd. Participants take 2 capsules (0.2g total) orally three times daily, 15-30 minutes before meals, for 48 weeks. This represents off-label use for cognitive impairment comorbid with epilepsy, as the drug is currently approved in China only for acute ischemic stroke treatment.
Placebo
DrugMatching placebo capsules identical in appearance, weight, and odor to butylphthalide soft capsules, manufactured by the same company following GMP standards. Participants take 2 capsules orally three times daily, 15-30 minutes before meals, for 48 weeks. Placebo contains starch and appropriate excipients.
Treatment groups
220 Participants
are divided into 2 treatment groupsGroup A: Butylphthalide GroupExperimental treatment 1 intervention
Group B: Placebo GroupPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
Change in Montreal Cognitive Assessment (MoCA) Total Score from Baseline to 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.
Time frame
Baseline and 48 weeksSecondary outcomes
1
Trail Making Test Part A (TMT-A) Completion Time Changes
Trail Making Test Part A (TMT-A) assesses visual scanning speed and psychomotor speed. Participants connect numbered circles in ascending order (1-2-3-4-5...-25). Completion time is measured in seconds, with typical ranges from 15-300 seconds depending on age and education. Lower completion times indicate better performance. The outcome is calculated as: (TMT-A time at assessment point) - (TMT-A time at baseline). A negative change indicates improvement.
Time frame
Baseline, 12 weeks, 24 weeks, 36 weeks, and 48 weeks2
Trail Making Test Part B (TMT-B) Completion Time Changes
Trail Making Test Part B (TMT-B) assesses executive function including cognitive flexibility and attention switching. Participants alternate between numbers and letters (1-A-2-B-3-C...). Completion time is measured in seconds, with typical ranges from 30-600 seconds depending on age and education. Lower completion times indicate better performance. The outcome is calculated as: (TMT-B time at assessment point) - (TMT-B time at baseline). A negative change indicates improvement.
Time frame
Baseline, 12 weeks, 24 weeks, 36 weeks, and 48 weeks3
Digit Span Forward Test Score Changes
Digit Span Forward Test assesses attention and short-term memory capacity. Participants repeat number sequences in the same order as presented. Scores range from 0 to 9 points, with higher scores indicating better attention and short-term memory performance. The outcome is calculated as: (Digit Span Forward score at assessment point) - (Digit Span Forward score at baseline). A positive change indicates improvement.
Time frame
Baseline, 12 weeks, 24 weeks, 36 weeks, and 48 weeks4
Digit Span Backward Test Score Changes
Digit Span Backward Test assesses working memory and mental manipulation abilities. Participants repeat number sequences in reverse order. Scores range from 0 to 8 points, with higher scores indicating better working memory performance. The outcome is calculated as: (Digit Span Backward score at assessment point) - (Digit Span Backward score at baseline). A positive change indicates improvement.
Time frame
Baseline, 12 weeks, 24 weeks, 36 weeks, and 48 weeksSponsors and contacts
Click on the lead sponsor to view all of their trials.
First Affiliated Hospital of Wenzhou Medical University
Lead sponsor
Taizhou Hospital
Collaborator
Lishui Country People's Hospital
Collaborator
Affiliated Yueqing Hospital of Wenzhou Medical University
Collaborator
The Third Affiliated Hospital of Wenzhou Medical University
Collaborator
Source ClinicalTrials.gov