NCT03451591

LACunar Intervention (LACI-2) Trial-2

LACunar Intervention (LACI-2) Trial-2: Assessment of Safety and Efficacy of Cilostazol and Isosorbide Mononitrate to Prevent Recurrent Lacunar Stroke and Progression of Cerebral Small Vessel Disease.

• Status: Completed
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 363 (actual)
• Sponsor: University of Edinburgh · Academic / Other
• Sex: All
• Age: 30 Years
• Healthy volunteers: Not accepted

Summary

About 35,000 people each year in the UK have a type of stroke, called 'lacunar' or 'small vessel' stroke, which is different to other common types of stroke and for which there is no proven treatment. It is thought that small vessel stroke is caused by damage to the lining of the tiny blood vessels deep inside the brain that stops them functioning normally. This not only causes stroke but, perhaps more importantly, causes problems with thinking and walking, possibly causing up to 45% of all dementias either on its own, or mixed with Alzheimer's disease (about 350,000 patients in the UK). Some drugs that are commonly used in other blood vessel diseases may help improve small vessel function and prevent worsening of brain damage. One drug (cilostazol) has been tested in patients with stroke in the Asia Pacific countries but not on dementia; the other drug (isosorbide mononitrate) is widely used in the UK for heart disease but not stroke. The investigators want to set up a clinical trial to test if the study methods are practical so that patients and trial centres can follow the procedures, and to confirm how many patients have more stroke-like symptoms or experience worsening of their thinking skills. This information is needed to be sure that a very large clinical trial to find out if these drugs can prevent worsening of small vessel disease will be possible.

Detailed description

A quarter of all ischaemic strokes (about 35000 per annum in the UK) are lacunar (small vessel) in type, mainly caused by an intrinsic, non-atheromatous, non-cardioembolic disease of the small deep perforating cerebral arterioles. More diffuse cerebral small vessel disease also causes up to 45% of dementias (350,000+ patients estimated currently in the UK), either alone or in association with Alzheimer's disease. There is no proven treatment for cerebral small vessel disease: conventional antiplatelet drugs may be ineffective or even hazardous, whilst antihypertensive treatment and statins may not have an effect. 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 cerebral small vessel disease. This trial will be an Phase IIb preparatory to Phase III, randomised, partial factorial, open label, blinded end-point trial, testing cilostazol, ISMN, both, or neither, to assess the feasibility of recruitment, drug tolerability, trial procedures, safety and event rates in 400 patients recruited in UK stroke centres and followed-up to one year (primary endpoint). This trial is preparatory to a large, definitive, Phase III randomised controlled trial to prevent recurrent lacunar stroke and progressive small vessel disease-related physical and cognitive impairments after lacunar stroke.

Conditions

• Cerebral Small Vessel Diseases
• Stroke, Lacunar

Interventions

Type	Name	Description
DRUG	Isosorbide Mononitrate XL (ISMN)	Isosorbide mononitrate (ISMN), is an NO donating organic nitrate that enhances vasodilation, is widely used in ischaemic heart disease, and has no antiplatelet activity.
DRUG	Cilostazol	Cilostazol is a phosphodiesterase 3-inhibitor (PDE3-inhibitor) that enhances the PGI2-cAMP system. It has weak antiplatelet effects (so low bleeding risk), reduces infarct size and reduces ageing-related decline in myelin repair in experimental models.
DRUG	ISMN XL and Cilostazol	Cilostazol is a phosphodiesterase 3-inhibitor (PDE3-inhibitor) that enhances the PGI2-cAMP system. It has weak antiplatelet effects (so low bleeding risk), reduces infarct size and reduces ageing-related decline in myelin repair in experimental models. Isosorbide mononitrate (ISMN), is an NO donating organic nitrate that enhances vasodilation, is widely used in ischaemic heart disease, and has no antiplatelet activity.
OTHER	Neither ISMN nor cilostazol	Neither isosorbide mononitrate nor Cilostazol administered for the entire duration of the study.

Timeline

• Start date: 2018-01-08
• Primary completion: 2022-05-31
• Completion: 2022-08-11
• First posted: 2018-03-02
• Last updated: 2024-11-12
• Results posted: 2024-11-12

Locations

1 site across 1 country: United Kingdom