LACunar Intervention trial – Cognition 1 (LACI-Cog1): a feasibility study of cilostazol and isosorbide mononitrate in vascular cognitive impairment
Vascular cognitive impairment in small vessel disease
Eligible participants will be randomized into one of four trial arms: ISMN alone, Cilostazol alone, both ISMN and cilostazol, or neither drug. Randomization will be conducted using REDCap, which uses a secure web-based application programming interface (API) hosted within the University of Edinburgh to allocate treatment groups using minimization techniques. Treatment duration is 8 weeks, with follow-up to 10 weeks. ISMN will be administered orally once daily, starting at 25 mg daily and titrated to a target dose of 50 mg daily. Cilostazol will be administered orally twice daily, starting at 50 mg twice daily and titrated to a target dose of 100 mg twice daily. Participants randomized to both drugs will follow a staggered dose-escalation schedule to improve tolerability. At the end of the treatment period, participants will be provided with instructions to gradually reduce and stop the trial medication over one week. A follow-up telephone call at week 10 will confirm treatment discontinuation and collect safety information. All trial arms will follow the same schedule of assessments and follow-up procedures.
1. Age ≥ 50 years. 2. Cognitive impairment* – mild cognitive impairment (abnormal cognitive testing in the view of the study investigator, but no functional impairment) or mild dementia (abnormal cognitive testing and functional impairment due to the cognitive problem). These diagnoses will be recorded in the medical notes. 3. A moderate to severe burden of cSVD on brain imaging (MRI or CT) within the last three years, defined as Fazekas score ≥2 in each of periventricular and deep regions (i.e., a total Fazekas score ≥4) or total Fazekas score ≥3 AND one or more lacunes. The brain imaging is performed as part of routine clinical care 4. The cSVD is considered to be a major contributor to the cognitive impairment in the opinion of the study investigator, documented in the medical record.** 5. Retained capacity to provide written consent themselves in the opinion of the study investigator. 6. Have a study partner*** who knows the participant sufficiently well to provide information about their functional abilities, in the view of the study investigator, and who is willing to join the study in this role. 7. Proficiency in written and spoken English to understand study materials and processes, in the view of the investigator, documented in the medical record. *We will not use upper or lower bound cut-offs on cognitive testing to determine eligibility, but participants must be able to provide consent themselves. For the mild cognitive impairment stage (cognitive decline but no resulting functional impairment), cognitive impairment will be deemed present if the most recent cognitive testing performed during clinical care (usually an Addenbrooke’s Cognitive Examination III) identifies lower than expected performance for that patient’s age and educational background. **Participants will be eligible if they are thought to have mixed pathology (e.g. vascular and Alzheimer’s disease), providing the vascular changes are considered to be the major contributor. Patients with ge
Current exclusion criteria as of 09/06/2026: 1. Unlikely to be able to manage medications without a dosette, based on information provided by the patient and family or carer. If a patient would be unable to manage their medications alone, but has sufficient family or carer support to take the trial medications in the view of the Principal Investigator, they can be included. 2. The cognitive impairment is thought to be mostly due to a cortical or large subcortical ischaemic or haemorrhagic stroke, rather than due to cSVD. This information will be contained within the medical record. 3. Significant active neurological illness, such as intractable epilepsy, multiple sclerosis, Parkinson’s disease, a neurodevelopmental disorder, or brain tumour. Well‑controlled epilepsy (for example, seizure‑free for more than 6 months) is not an exclusion criterion. 4. Hypotension, defined as sitting systolic blood pressure less than 100 mmHg. 5. Definite indication for (that is, already prescribed) either trial medication, or definite contraindication to both trial drugs as per SPCs. Lactose intolerance is a contraindication to ISMN preparations which contain lactose monohydrate. Having an indication for or contraindication to one of the trial drugs still allows randomisation to the other trial drug. 6. Unable to swallow tablets, based on information provided by the patient and/or their family or carer. 7. Planned surgery during the trial period. 8. Other concurrent life‑threatening illness, with life expectancy expected to be less than 1 year in the view of the study investigator. 9. Unlikely to be available for follow‑up (for example, moving outside of the area). 10. History of drug overdose, attempted suicide, or significant active mental illness documented in the medical notes. 11. Women of childbearing potential. Women of childbearing potential (WOCBP), defined in line with the Clinical Trials Coordination Group (CTCG; March 2024) guidance as fertile following menarche (and havin