Clinical Trial: Lacunar Intervention Trial 1 (LACI-1)

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Preventing Cognitive Decline and Dementia From Cerebral Small Vessel Disease

Brief 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 Summary: 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.
Sponsor: University of Edinburgh

Current Primary Outcome: Tolerability proportion of patients able to tolerate the target dose [ Time Frame: 8 weeks ]

proportion of patients able to tolerate the target dose


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Safety - bleeding [ Time Frame: 12 weeks ]
    systemic or intracranial bleeding
  • Safety - recurrent stroke [ Time Frame: 12 weeks ]
    recurrent vascular events,
  • Safety - death [ Time Frame: 12 weeks ]
    death
  • Safety - blood pressure [ Time Frame: 8 weeks ]
    reduction in blood pressure
  • Safety - bleeding [ Time Frame: 8 weeks ]
    effect on platelet function assessed using p-selectin
  • Efficacy - cerebrovascular function [ Time Frame: 8 weeks ]
    effect on cerebrovascular reactivity assessed using carbon dioxide challenge in magnetic resonance imaging
  • Efficacy - systemic arterial stiffness [ Time Frame: 8 weeks ]
    effect on systemic large artery stiffness assessed with pulse wave velocity measurement
  • Tolerability Proportion of patients with headache that interferes with daily activities [ Time Frame: 8 weeks ]
    Proportion of patients with headache that interferes with daily activities
  • Tolerability Proportion of patients with dizziness that interferes with daily activities [ Time Frame: 8 weeks ]
    Proportion of patients with dizziness that interferes with daily activities
  • Tolerability Proportion of patients with nausea that interferes with daily activities [ Time Frame: 8 weeks ]
    Proportion of patients with nausea that interferes with daily activities
  • Tolerability Proportion of patients with palpitations [ Time Frame: 8 weeks ]
    Proportion of patients with palpitations
  • Tolerability Proportion of patients with loose stools [ Time Frame: 8 weeks ]
    Proportion of patients with loose stools
  • Tolerability Tablet count [ Time Frame: 8 weeks ]
    Tablet count


Original Secondary Outcome: Same as current

Information By: University of Edinburgh

Dates:
Date Received: June 19, 2015
Date Started: October 2015
Date Completion: September 2017
Last Updated: May 10, 2016
Last Verified: May 2016