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.
Huashan Hospital
Lead sponsor
Jiangsu Simcere Pharmaceutical Co., Ltd.
Collaborator