Developing treatments for cerebral small vessel disease: a scoping review of licensed interventions for potential repurposing
Abstract
Background: Cerebral small vessel disease (cSVD) is a progressive neurovascular-degenerative condition without specific treatment that causes lacunar stroke, most intracerebral haemorrhage, vascular cognitive impairment (VCI) and several neuropsychiatric conditions.
Objectives: To conduct a rapid multi-stage scoping review to identify licensed interventions that could be repurposed for testing in cSVD at phase-3.
Methods: First, we screened preclinical studies of potential relevance to cSVD and used a drug dictionary to identify studies of potential interventions. Separately, we screened clinical studies of relevance to cSVD and VCI. Following merging, we removed drugs that were unsuitable or impractical to assess long-term in the UK. We then performed mini-meta-analyses for shortlisted interventions assessing effects on cognition and scored these for their relevance to cSVD.
Results: The preclinical review created a long-list of 1,757 deduplicated interventions. Those that were available in the UK, not expensive or impractical to administer long-term were merged with 62 interventions identified from 75 relevant clinical studies to create a medium-list of 52 interventions. Focussed literature review short-listed ten interventions for review by an Independent Scientific Advisory Group; they ranked three as most suitable for immediate testing: metformin, tadalafil and isosorbide mononitrate.
Conclusion: This rapid review identified three interventions that are suitable for…
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