Vascular cognitive impairment in small vessel disease Nervous System Diseases
Conditions
Interventions
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
Sponsors
University of Edinburgh
NHS Lothian
Eligibility
Sex/Gender
All
Age
50 Years to 120 Years
Inclusion criteria
Inclusion criteria: 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 genetic SVD (e.g. CADASIL) will be eligible if presenting with cognitive impairment and meeting the other inclusion criteria. Added 09/06/2026: ***A study partner is usually someone who lives with the participant (e.g., a spouse) or a close relative or friend who is in regular contact (at least weekly) and knows the participant well enough to comment on their day-to-day functioning. The study partner must have known the participant for a sufficient period and have regular contact to provide a meaningful assessment of cognitive change over time using the IQCODE. Suitability of the study partner will be determined by the Principal Investigator (or delegated qualified investigator) at screening. The study partner may, but is not required to be, the participant’s welfare guardian or Power of Attorney.
Exclusion criteria
Exclusion criteria: 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 having not been free from menses for >1 year), and until becoming post-menopausal (no menses for 12 months without an alternative medical cause) unless permanently sterilised by hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) will not be eligible for this single-centre short-term IMP administration pilot trial. Firstly, women of childbearing potential with VCI due to cSVD are extremely rare, and secondly, LACI-Cog-1 is a small, single-centre, short-term administration trial focused on the feasibility of recruitment and tolerance of IMP in a population that is more typical of patients attending memory clinics. 12. Prohibited medications to either trial drug. Prohibited medications to one of the trial drugs still allow randomisation to the other trial drug. 13. Renal impairment, defined as creatinine clearance less than 25 ml/min. 14. Moderate to severe hepatic impairment. 15. No renal or hepatic function tests within the last 12 months. 16. Previous participation in previous LACI trials (LACI-1, LACI-2, and LACI-3). 17. Participation in another Clinical Trial of an Investigational Medicinal Product, up to and including at least five half-lives after the last dose of that Investigational Medicinal Product. Cilostazol exclusion criteria (still allows randomisation to ISMN): 1. Definite indication for (that is, already prescribed) Cilostazol, or definite contraindication to cilostazol as per SPC section 4.3. 2. Prohibited medications to cilostazol (see appended SPCs
Countries
Scotland, United Kingdom
Contacts
Public ContactJoanna;Daniela Jaime Wardlaw;Garcia
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Outcome results
None listed