Retina is a Marker for Cerebrovascular Heath

Retinal Vasoreactivity is a Marker for Cerebral Small Vessel Disease Progression

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.

Study Overview

• Status: Recruiting
• Conditions: Cerebral Small Vessel Diseases; Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy; Cerebral Microbleeding; Sporadic White Matter Disease
• Intervention / Treatment: Drug: Cilostazol

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 Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Meredith McDonald; Phone Number: 904-953-4200; Email: mcdonald.meredith@mayo.edu

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic Florida
      • Contact: Meredith McDonald; Phone Number: 904-953-4200; Email: mcdonald.meredith@mayo.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: No intervention
Experimental: Cilostazol; Cilostazol 100mg BID	Drug: Cilostazol; Cilostazol 100mg BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
white matter disease volume	change in total white matter disease volume	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cognition	global Z-score and by cognitive domain	1 year
stroke	ischemic stroke or hemorrhagic stroke	1 year
cerebrovasoreactivity	change in blood oxygen level dependence (BOLD) per unit of end tidal PCO2 mmHg	1 year
retinal vasoreactivity	change in retinal vessel density pre/post CO2 challenge	1 year

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Michelle P Lin, MD, MPH, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): February 9, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: February 9, 2021
• First Submitted That Met QC Criteria: February 9, 2021
• First Posted (Actual): February 15, 2021

Study Record Updates

• Last Update Posted (Actual): July 23, 2025
• Last Update Submitted That Met QC Criteria: July 21, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Mental Disorders; Pathologic Processes; Genetic Diseases, Inborn; Neurocognitive Disorders; Brain Infarction; Brain Ischemia; Infarction; Necrosis; Dementia; Ischemia; Intracranial Arterial Diseases; Stroke; Cerebral Arterial Diseases; Cerebral Infarction; Dementia, Vascular; Leukoencephalopathies; CADASIL; Dementia, Multi-Infarct; Cerebral Small Vessel Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Fibrin Modulating Agents; Fibrinolytic Agents; Platelet Aggregation Inhibitors; Protective Agents; Respiratory System Agents; Anti-Asthmatic Agents; Bronchodilator Agents; Vasodilator Agents; Neuroprotective Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Cilostazol
• Other Study ID Numbers: 20-000087

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No