Retina is a Marker for Cerebrovascular Heath
Study Details
Study Description
Brief Summary
Cerebral small vessel disease (SVD), present in 80-94% of adults over age 65 years, increases the risk of stroke by 2-fold, and dementia by 2.3-fold. There is currently no treatment to slow SVD progression. This study aims to test whether impaired cerebral and retinal vasoreactivity may serve as biomarker for SVD progression, and to evaluate the safety and efficacy of cilostazol (antiplatelet agent with vasodilatory and anti-inflammatory properties) for the treatment of SVD.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
This is a prospective, observational nested pilot randomized controlled study to discover retinal biomarkers that would predict cerebral small vessel disease progression, and evaluate the safety/efficacy of cilostazols in slowing SVD progression. Twenty CADASIL, 40 sWMD, 20 lobar CMB, and 20 age-matched healthy controls from the Mayo Clinic Florida Familial Cerebrovascular Disease Registry and neurology clinic will be recruited. All participants will undergo OCTA retinal scan, MRI-BOLD brain scan, cognitive battery evaluation, and blood sample at baseline and a 12-month follow-up visit. Key outcome measures are: RVR, CVR, cognition, WMH volume, and CMB volume. The 40 patients diagnosed in the course of routine clinical care with sWMD will be randomized in 1:1 ratio to receive cilostazol 100mg bid (or 50 mg bid if taking medications known to affect metabolism of cilostazol) or no cilostazol, and followed for WMD progression, and secondarily for changes in cognition, RVR and CVR. Flow diagram below outlines the study design. Note that in addition to what is shown in the trial flow diagram, patients will have telephone visits between baseline and 12 month clinic visits biweekly for 3 months and then monthly thereafter. These visits will consist of a survey for adverse events and at the 1-, 3-, 6- and 9-month telephone visits patients will also get a modified Rankin scale assessment, a Six-item screener (cognitive assessment) and a PHQ-2 (depression screen).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cilostazol Cilostazol 100mg BID |
Drug: Cilostazol
Cilostazol 100mg BID
|
| No Intervention: No intervention
|
Outcome Measures
Primary Outcome Measures
- white matter disease volume [1 year]
change in total white matter disease volume
Secondary Outcome Measures
- cognition [1 year]
global Z-score and by cognitive domain
- stroke [1 year]
ischemic stroke or hemorrhagic stroke
- cerebrovasoreactivity [1 year]
change in blood oxygen level dependence (BOLD) per unit of end tidal PCO2 mmHg
- retinal vasoreactivity [1 year]
change in retinal vessel density pre/post CO2 challenge
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age ≥18 yo.
-
Diagnosis of CADASIL, sporadic WMD or lobar CMB and age-matched healthy controls (eg. patient's spouse or unrelated friends without SVD)
Exclusion Criteria:
-
Age<18yo
-
Pregnant
-
Breast feeding
-
Unable to follow commands
-
Unable to tolerate MRI
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic in Florida | Jacksonville | Florida | United States | 32224 |
Sponsors and Collaborators
- Mayo Clinic
Investigators
- Principal Investigator: Michelle Lin, MD, MPH, Mayo Clinic
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 20-000087