NCT02481323

Lacunar Intervention Trial 1 (LACI-1)

Preventing Cognitive Decline and Dementia From Cerebral Small Vessel Disease

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 57 (actual)
• Sponsor: University of Edinburgh · Academic / Other
• Sex: All
• Age: 35 Years
• Healthy volunteers: Not accepted

Summary

Phase II pilot randomised, factorial, short term dose escalation, open label, blinded intermediary endpoint trial, in two hospital centres in the UK, of tolerability and safety of cilostazol, isosorbide mononitrate, both or neither in patients with small vessel disease manifest as symptomatic small subcortical stroke.

Detailed description

A quarter of all ischaemic strokes are lacunar (small vessel) in type, about 35000 per annum in the United Kingdom, and due to an intrinsic, non-atheromatous, non-cardioembolic perforating cerebral arteriolar disease. 'Small vessel disease' also affects the brain diffusely, causing up to 40% of dementias, alone or mixed with Alzheimer's disease, 350,000+ patients estimated currently in the United Kingdom. There is no proven treatment: conventional antiplatelet drugs may be ineffective or even hazardous, antihypertensive treatment and statins have been disappointing. The disease mechanism is poorly understood but endothelial dysfunction, blood-brain barrier failure and vessel stiffness appear to contribute to the pathogenesis. Promising data available for licensed drugs with relevant modes of action, cilostazol (\>6000 stroke patients in the Asia Pacific region) and isosorbide mononitrate (ISMN, widely used in cardiac disease) support their testing in small vessel disease. This trial will be a phase 2, randomised, dose-escalation, factorial trial to test short-term administration of cilostazol, Isosorbide Mononitrate, both, or neither, to provide data on patient tolerability of dose (including headache, dizziness), safety (including blood pressure, platelet function), provide mechanistic evidence of efficacy (cerebrovascular reactivity, arterial compliance), and to inform the design of a larger phase 2-3 trial. The trial will recruit 60 patients with small vessel disease, in two expert stroke centres (Edinburgh and Nottingham) where there are suitable patients, expert stroke centres, established trials infrastructures and neuroimaging and platelet testing expertise. The trial will also advance methods to stratify patients by small vessel disease burden in routine practise and data on intermediary mechanistic outcomes to assist in planning future trials testing novel agents for either stroke or dementia.

Conditions

• Cerebral Small Vessel Diseases
• Cognitive Impairment
• Stroke

Interventions

Type	Name	Description
DRUG	isosorbide mononitrate	slow release nitric oxide donor that enhances vasodilation and widely used in angina prophyaxis
DRUG	cilostazol	phosphodiesterase 3-inhibitor that enhances vessel wall function with weak antiplatelet effects

Timeline

• Start date: 2016-03-01
• Primary completion: 2017-08-01
• Completion: 2017-11-30
• First posted: 2015-06-25
• Last updated: 2018-01-19

Locations

2 sites across 1 country: United Kingdom