Safety and Efficacy of Edaravone Dexborneol Sublingual Tablets for Blood-Brain Barrier Dysfunction in CADASIL

NCT07692399 | Not Yet Recruiting Phase 2

• 1 other identifier: KY2026-703
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

CADASIL

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline, Month 6, and Month 12

Secondary Outcomes (34)

• Clinical Stroke Events

  12 months

• Change in Montreal Cognitive Assessment (MoCA) Score

  Baseline, Month 6, and Month 12

• Change in Auditory Verbal Learning Test (AVLT) Score

  Baseline, Month 6, and Month 12

• Change in Boston Naming Test Score

  Baseline, Month 6, and Month 12

• Change in Stroop Color-Word Test completion time

  Baseline, Month 6, and Month 12

Study Arms (1)

Edaravone Dexborneol Sublingual Tablets

EXPERIMENTAL

All enrolled participants follow a two-phase, self-controlled schedule. During the first 6 months (natural history observation period), participants do not receive the study drug and continue their routine standard care for CADASIL. During the subsequent 6 months (treatment period), participants receive edaravone dexborneol sublingual tablet in addition to their routine standard care.

Drug: Edaravone Dexborneol Sublingual Tablets

Interventions

Edaravone Dexborneol Sublingual Tablets DRUG

One tablet (containing edaravone 30 mg and dexborneol 6 mg) is taken sublingually twice daily for the 6-month treatment period.

Edaravone Dexborneol Sublingual Tablets

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Genetically Confirmed CADASIL: Diagnosis of CADASIL confirmed by NOTCH3 genetic testing.
• \. Age: Between 18 and 80 years.
• \. Lacunar Lesion Requirement: Presence of ≥1 lacune on brain MRI.
• \. No acute ischemic stroke or intracerebral hemorrhage within the past 3 months.
• \. Modified Rankin Scale (mRS) score of 0 to 3.
• \. Contraception Requirements: Women of childbearing potential and male participants with female partners of childbearing potential must agree to use effective contraception during the study and 30 days after the last dose of the investigational drug.Female participants must have a negative pregnancy test before enrollment.
• \. Informed Consent: Participants or their legal representatives must voluntarily sign an informed consent form (ICF).

You may not qualify if:

• \. 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.
• \. Severe Liver Dysfunction: Active liver disease (acute hepatitis, chronic active hepatitis, cirrhosis) or ALT/AST \>2× ULN.
• \. Severe renal impairment (serum creatinine \>1.5× ULN).
• \. Life Expectancy \<1 year due to severe systemic diseases.
• \. Contraindications to MRI: Participants with MRI-incompatible implants, severe claustrophobia, or inability to undergo MRI.
• \. Known Allergies: History of hypersensitivity to Dexborneol, natural borneol, edaravone, or any excipients (e.g., mannitol, copovidone, microcrystalline cellulose, silica, magnesium stearate).
• \. Pregnancy and Lactation: Pregnant or lactating women, or those planning pregnancy during the study period.
• \. Participation in Other Clinical Trials
• \. Other Investigator-Determined Factors: Any other medical, psychological, or social condition that, in the investigator's judgment, makes the patient unsuitable for participation.

Sponsors & Collaborators

• Huashan Hospital: lead
• Jiangsu Simcere Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Huashan Hospital, Fudan University

Shanghai, China

Location

MeSH Terms

Conditions

CADASIL

Condition Hierarchy (Ancestors)

Cerebral Infarction; Brain Infarction; Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Dementia, Vascular; Cerebral Arterial Diseases; Intracranial Arterial Diseases; Stroke; Dementia; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Central Study Contacts

Xin Cheng

CONTACT

+86 021-52887145; chengxin@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Vice Chair, Department of Neurology, Huashan Hospital, Fudan University

Study Record Dates

• First Submitted: June 29, 2026
• First Posted: July 9, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: July 9, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)