This page tracks active and recent clinical trials targeting vascular dementia (VaD), vascular cognitive impairment (VCI), and cerebral small vessel disease (CSVD). Unlike Alzheimer's disease, VaD has fewer disease-modifying therapies in development, with current focus on vascular risk modification, neuroprotection, and cognitive enhancement.
| Phase |
VaD/VCI Trials |
Notes |
| Phase 1 |
~5 |
Mostly targeting vascular mechanisms |
| Phase 2 |
~15 |
Cognitive endpoints, BP modification |
| Phase 3 |
~10 |
Largest studies focus on secondary prevention |
SPRINT-MIND (NCT01206062)
- Population: Adults with hypertension, aged ≥55 years
- Intervention: Intensive BP control (SBP <120 mmHg) vs standard (<140 mmHg)
- Outcome: Incident MCI, all-cause dementia, white matter lesion progression
- Status: Completed
- Key Finding: Intensive control reduced risk of mild cognitive impairment by 24% and combined MCI/dementia by 19%
- Reference: https://clinicaltrials.gov/ct2/show/NCT01206062
LACI-1 (NCT03131289)
- Population: Lacunar stroke patients with small vessel disease
- Intervention: Cilostazol + isosorbide mononitrate vs placebo
- Outcome: Endothelial function, white matter lesion progression
- Status: Completed
- Key Finding: Combination therapy improved cerebrovascular reactivity
LACI-2 (ISRCTN10506409)
- Population: Lacunar stroke survivors
- Intervention: Dual antiplatelet therapy (clopidogrel + aspirin) vs aspirin alone
- Outcome: Recurrent stroke, cognitive decline
- Status: Completed
- Reference: https://clinicaltrials.gov/ct2/show/NCT03131289
Cerebrolysin Studies
- Mechanism: Neurotrophic factor mixture
- Phase: 2-3
- Population: Vascular dementia patients
- Outcomes: Cognitive function, global clinical impression
- Status: Mixed results; larger trials needed
Citicoline (CDP-Choline)
- Mechanism: Membrane stabilizer, supports acetylcholine synthesis
- Phase: 2-3
- Population: Vascular cognitive impairment
- Outcomes: Memory, executive function
- Note: Historical trials showed mixed results
MINDS (NCT02740984)
- Population: Small vessel disease with cognitive impairment
- Intervention: Minocycline (anti-inflammatory)
- Outcome: White matter lesion progression, cognitive scores
- Status: Completed
PROPEL (NCT02831188)
- Population: Vascular cognitive impairment
- Intervention: Propentofylline (phosphodiesterase inhibitor)
- Outcome: Cerebral blood flow, cognitive function
- Status: Completed
| Agent |
Mechanism |
Target |
Status |
| BTI202 |
PDE5 inhibitor |
Cerebral vasodilation |
Phase 1 |
| NGP-5555 |
Anti-amyloid (vascular) |
CAA in VCI |
Phase 1 |
| CNB-001 |
Neuroprotective |
Akt/GSK3β |
Phase 1 |
| Drug |
Mechanism |
Reason for Failure |
| Enoxaparin |
Anticoagulant |
Bleeding risk exceeded benefit |
| Xanapezine |
Vasodilator |
Lack of efficacy |
| S-(-)-efar |
Calcium channel |
Insufficient cognition benefit |
- Single-target approaches limited: Multi-target therapies may be needed given the heterogeneous vascular pathology
- Timing matters: Early intervention before significant white matter damage appears more effective
- Mixed pathology: Many patients with VaD also have AD pathology, complicating trial design and endpoint selection
- White matter hyperintensity (WMH) volume: Primary imaging endpoint
- Diffusion tensor imaging (DTI): Microstructural integrity
- Cerebral blood flow (ASL): Perfusion measures
- Susceptibility-weighted imaging (SWI): Microbleed detection
| Biomarker |
Utility |
| Neurofilament light chain (NfL) |
Axonal damage, disease progression |
| Glial fibrillary acidic protein (GFAP) |
Astrocyte activation |
| Tau (total and phosphorylated) |
Neuronal injury, AD co-pathology |
| Amyloid-beta 40/42 |
AD co-pathology assessment |
- MMSE: Global cognition
- MoCA: Executive function sensitive
- EXIT25: Frontal/executive function
- Vascular Dementia Assessment Scale (VaDAS): VaD-specific
- ADAS-Cog: Modified for vascular features
Cog-VACS (NCT05287474)
- Population: Post-stroke cognitive impairment
- Intervention: Computerized cognitive training + BP management
- Outcome: Composite cognitive score at 12 months
- Status: Recruiting
THALES-2 (NCT04676551)
- Population: Acute lacunar stroke
- Intervention: Ticagrelor + aspirin vs aspirin alone
- Outcome: New ischemic lesions on MRI, cognitive function
- Status: Recruiting
CADASIL-BMS (NCT04052737)
- Population: CADASIL patients
- Intervention: BMS-986012 (anti-Notch3)
- Outcome: Safety, cognitive endpoints
- Status: Phase 1
| Institution |
Focus |
| University of Edinburgh |
CSVD imaging, white matter |
| UCL Institute of Neurology |
Vascular cognitive impairment |
| University of Pittsburgh |
Cerebral autoregulation |
| Maastricht University |
CSVD genetics |
| Karolinska Institutet |
Vascular mechanisms |