This study is a single-center, prospective, single-arm, self-controlled clinical trial designed to assess the safety and efficacy of edaravone dexborneol sublingual tablets for blood-brain barrier (BBB) dysfunction in patients with CADASIL.
The study will enroll approximately 60 participants aged 18 to 80 years with genetically confirmed CADASIL. Participants will be followed for a total duration of 12 months, including two consecutive phases.
* Phase 1 is a 6-month natural history observation period, during which participants do not receive the study drug and continue their routine standard care for CADASIL. * Phase 2 is a 6-month drug intervention period, in which participants will receive edaravone dexborneol sublingual tablets to investigate the effect on the BBB water exchange rate (kw), measured by diffusion-prepared pseudo-continuous arterial spin labeling (DP-pCASL) MRI, and to assess potential benefits on stroke risk reduction, cognitive function, and gait performance.
The primary endpoint is the change in kw measured by DP-pCASL. Secondary endpoints include the incidence of clinical stroke events; changes in neuropsychological performance, MRI-based CSVD biomarkers, gait and motor assessments, functional disability and activities-of-daily-living scales, and peripheral blood biomarkers. Safety assessments will include adverse events (AEs) and serious adverse events (SAEs).
1. Genetically Confirmed CADASIL: Diagnosis of CADASIL confirmed by NOTCH3 genetic testing.
2. Age: Between 18 and 80 years.
3. Lacunar Lesion Requirement: Presence of ≥1 lacune on brain MRI.
4. No acute ischemic stroke or intracerebral hemorrhage within the past 3 months.
1. Presence of other major neurological disorders: Non-vascular white matter diseases (e.g., multiple sclerosis, carbon monoxide encephalopathy), central nervous system infections, Creutzfeldt-Jakob disease, primary Parkinson's disease, traumatic brain injury, or intracranial tumors.
2. Severe Liver Dysfunction: Active liver disease (acute hepatitis, chronic active hepatitis, cirrhosis) or ALT/AST >2× ULN.
3. Severe renal impairment (serum creatinine >1.5× ULN).
4. Life Expectancy <1 year due to severe systemic diseases.
Single group
Edaravone Dexborneol Sublingual Tablets
DrugOne tablet (containing edaravone 30 mg and dexborneol 6 mg) is taken sublingually twice daily for the 6-month treatment period.
Change in whole-brain blood-brain barrier water exchange rate (kw) measured by DP-pCASL MRI
The blood-brain barrier (BBB) water exchange rate (kw), an imaging marker of BBB function, is quantified on whole-brain diffusion-prepared pseudo-continuous arterial spin labeling (DP-pCASL) MRI at baseline, month 6, and month 12. All participants are untreated during the first 6 months (observation period) and receive edaravone dexborneol sublingual tablets during the subsequent 6 months (treatment period). The change in kw during the observation period (baseline to Month 6) is compared with the change during the treatment period (Month 6 to Month 12) to distinguish the natural trajectory of BBB dysfunction from a potential treatment effect.
Clinical Stroke Events
Number and proportion of participants experiencing any stroke event, including ischemic stroke and hemorrhagic stroke, recorded throughout the study.
Change in Montreal Cognitive Assessment (MoCA) Score
The Montreal Cognitive Assessment (MoCA) is a cognitive screening tool that assesses multiple domains, including attention, concentration, executive function, memory, language, visuospatial skills, abstract thinking, calculation, and orientation. Scores range from 0 to 30, with higher scores indicating better cognitive function.
Change in Auditory Verbal Learning Test (AVLT) Score
Verbal episodic memory is assessed using the Huashan version of the Auditory Verbal Learning Test (AVLT-H). The test uses a list of 12 words from three semantic categories (4 words per category). The examiner reads the list aloud and the participant recalls the words immediately; this is repeated for three consecutive trials. The immediate recall score is the sum of correctly recalled words across the three trials, ranging from 0 to 36, with higher scores indicating better memory function.
Change in Boston Naming Test Score
The Boston Naming Test (BNT) is a widely used neuropsychological assessment that measures confrontation naming-the ability to retrieve and produce the correct name for a visually presented object. Boston Naming Test includes 30 items and evaluates language through measuring the total of correct responses. The minimum score is 0, and the maximum score is 30. Higher score indicates better language.
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Huashan Hospital
Lead sponsor
Jiangsu Simcere Pharmaceutical Co., Ltd.
Collaborator
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