Butylphthalide for Cognitive Impairment in Elderly Patients With Focal Epilepsy

NCT07193277 | Recruiting Phase 4

• 1 other identifier: KY2025-330
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Focal Epilepsy; Cognitive Impairment

Keywords

Butylphthalide; Focal Epilepsy; Cognitive Impairment; Elderly; MoCA; Neuroprotection; Randomized Controlled Trial; Double-blind; Placebo-controlled; Multicenter

Outcome Measures

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.

  Baseline and 48 weeks

Secondary Outcomes (15)

• Trail Making Test Part A (TMT-A) Completion Time Changes

  Baseline, 12 weeks, 24 weeks, 36 weeks, and 48 weeks

• 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

• Digit Span Backward 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

Study Arms (2)

Butylphthalide Group

EXPERIMENTAL

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.

Drug: Butylphthalide

Placebo Group

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Butylphthalide DRUG

Butylphthalide 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.

Also known as: DL-3-n-butylphthalide, NBP

Butylphthalide Group

Placebo DRUG

Matching 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.

Placebo Group

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• First Affiliated Hospital of Wenzhou Medical University: lead
• 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

Study Sites (1)

First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, 325000, China

RECRUITING

MeSH Terms

Conditions

Epilepsies, Partial; Cognitive Dysfunction

Interventions

3-n-butylphthalide

Condition Hierarchy (Ancestors)

Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Huiqin Xu, MD

  Department of Neurology, First Affiliated Hospital of Wenzhou Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Huiqin Xu, MD

CONTACT

+86-13858806368; xuhuiqin@wmu.edu.cn

Jiahe Lin, PhD

CONTACT

+86-13587572321; linjiahe@wmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind design where participants, care providers, investigators, and outcomes assessors are masked to treatment assignment. Emergency unblinding procedures are available when medically necessary.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomly assigned in a 1:1 ratio to receive either butylphthalide soft capsules or matching placebo for 48 weeks. Both groups will continue their stable anti-seizure medication regimen throughout the study period.

Study Record Dates

• First Submitted: September 10, 2025
• First Posted: September 25, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): September 1, 2028
• Last Updated: September 25, 2025

Record last verified: 2025-09

Locations

CN (1)