NCT07692399尚未招募2 期
Safety and Efficacy of Edaravone Dexborneol Sublingual Tablets for Blood-Brain Barrier Dysfunction in CADASIL: A Single-Center, Prospective, Single-Arm, Self-Controlled Clinical Trial.
适应症
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Change in whole-brain blood-brain barrier water exchange rate (kw) measured by DP-pCASL MRI
研究概览
简要总结
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).
详细描述
This study is a single-center, prospective, single-arm, self-controlled clinical trial evaluating the safety and efficacy of edaravone dexborneol sublingual tablets for blood-brain barrier (BBB) dysfunction in CADASIL patients.
- Background and Rationale CADASIL is the most common monogenic form of cerebral small vessel disease (CSVD), caused by pathogenic mutations in the NOTCH3 gene. BBB dysfunction is increasingly recognized as one of the core pathophysiological mechanisms in CADASIL, contributing to white matter injury, progressive cognitive decline, and recurrent stroke, and represents a potential therapeutic target. Edaravone Dexborneol, a novel free radical scavenger and anti-inflammatory agent, has shown neuroprotective effects in preclinical models and clinical trials for ischemic stroke. The TASTE-SL trial demonstrated that edaravone dexborneol improved 90-day functional outcomes in patients with acute ischemic stroke. Based on these findings, this study is designed to systematically assess the efficacy and safety of edaravone dexborneol sublingual tablets in ameliorating BBB dysfunction in patients with CADASIL, and to investigate their potential benefits in reducing stroke risk and improving cognitive function.
- Study Design and Methods A total of 60 participants aged 18 to 80 years with genetically confirmed CADASIL will be recruited. The primary endpoint is the change in the BBB water-exchange rate (kw), measured by diffusion-prepared pseudo-continuous arterial spin labeling (DP-pCASL) MRI. The trial consists of two sequential phases: during the first 6 months (natural disease observation period), participants do not receive the study drug and continue their routine standard care for CADASIL, allowing for the characterization of intra-individual natural variability of kw. During the subsequent 6 months (treatment period), all participants will receive edaravone dexborneol sublingual tablets in addition to their routine standard care, and treatment-related changes in kw will be evaluated. All participants will undergo multimodal MRI scanning at baseline, month 6, and month 12, along with comprehensive assessments including cognitive testing, clinical scales, and peripheral blood biomarkers.
- Significance This study is expected to fill a significant gap in pharmacological intervention research for CADASIL and provide clinical evidence supporting the potential extension of edaravone dexborneol to genetically mediated small vessel disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •5. Modified Rankin Scale (mRS) score of 0 to
- •6. 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.
- •7. Informed Consent: Participants or their legal representatives must voluntarily sign an informed consent form (ICF).
排除标准
- •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.
- •5. Contraindications to MRI: Participants with MRI-incompatible implants, severe claustrophobia, or inability to undergo MRI.
- •6. Known Allergies: History of hypersensitivity to Dexborneol, natural borneol, edaravone, or any excipients (e.g., mannitol, copovidone, microcrystalline cellulose, silica, magnesium stearate).
- •7. Pregnancy and Lactation: Pregnant or lactating women, or those planning pregnancy during the study period.
- •8. Participation in Other Clinical Trials
- •9. Other Investigator-Determined Factors: Any other medical, psychological, or social condition that, in the investigator's judgment, makes the patient unsuitable for participation.
结局指标
主要结局
Change in whole-brain blood-brain barrier water exchange rate (kw) measured by DP-pCASL MRI
时间窗: Baseline, Month 6, and Month 12
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.
次要结局
- 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)
- Change in Stroop Color-Word Test number of correct responses(Baseline, Month 6, and Month 12)
- Change in Symbol Digit Modalities Test (SDMT) Score(Baseline, Month 6, and Month 12)
- Change in Trail Making Test (TMT) Score(Baseline, Month 6, and Month 12)
- Change in Digit Span Test (DST) Score(Baseline, Month 6, and Month 12)
- Change in Hamilton Anxiety Rating Scale (HAMA) score(Baseline, Month 6, and Month 12)
- Change in Hamilton Depression Rating Scale (HAMD) score(Baseline, Month 6, and Month 12)
- Change in number of lacunes(Baseline, Month 6, and Month 12)
- Change in Number of Microbleeds(Baseline, Month 6, and Month 12)
- Change in White Matter Hyperintensity Volume(Baseline, Month 6, and Month 12)
- Change in perivascular space (PVS) score(Baseline, Month 6, and Month 12)
- Change in total brain volume(Baseline, Month 6, and Month 12)
- Change in fractional anisotropy (FA)(Baseline, Month 6, and Month 12)
- Change in mean diffusivity (MD)(Baseline, Month 6, and Month 12)
- Change in peak width of skeletonized mean diffusivity (PSMD)(Baseline, Month 6, and Month 12)
- Change in Tinetti Balance and Gait Assessment score(Baseline, Month 6, and Month 12)
- Changes in Short Physical Performance Battery (SPPB) score(Baseline, Month 6, and Month 12)
- Change in modified Rankin Scale (mRS) score(Baseline, Month 6, and Month 12)
- Change in Instrumental Activities of Daily Living (IADL) scale score(Baseline, Month 6, and Month 12)
- Change in serum neurofilament light chain (NfL)(Baseline, Month 6, and Month 12)
- Change in serum high-sensitivity C-reactive protein (hs-CRP)(Baseline, Month 6, and Month 12)
- Change in serum interleukin-6 (IL-6)(Baseline, Month 6, and Month 12)
- Change in serum interleukin-8 (IL-8)(Baseline, Month 6, and Month 12)
- Change in serum interleukin-10 (IL-10)(Baseline, Month 6, and Month 12)
- Change in serum tumor necrosis factor-alpha (TNF-α)(Baseline, Month 6, and Month 12)
- Change in serum glial fibrillary acidic protein (GFAP)(Baseline, Month 6, and Month 12)
- Adverse events(12 months)
- Serious adverse events(12 months)
- Liver function impairment(12 months)
- Renal function impairment(12 months)
研究者
Xin Cheng
Professor and Vice Chair, Department of Neurology, Huashan Hospital, Fudan University
Huashan Hospital
研究点 (1)
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