Retina is a Marker for Cerebrovascular Heath
Primary Purpose
Cerebral Small Vessel Diseases, Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy, Cerebral Microbleeding
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Cilostazol
Sponsored by
About this trial
This is an interventional prevention trial for Cerebral Small Vessel Diseases
Eligibility 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
Sites / Locations
- Mayo Clinic FloridaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Cilostazol
No intervention
Arm Description
Cilostazol 100mg BID
Outcomes
Primary Outcome Measures
white matter disease volume
change in total white matter disease volume
Secondary Outcome Measures
cognition
global Z-score and by cognitive domain
stroke
ischemic stroke or hemorrhagic stroke
cerebrovasoreactivity
change in blood oxygen level dependence (BOLD) per unit of end tidal PCO2 mmHg
retinal vasoreactivity
change in retinal vessel density pre/post CO2 challenge
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04753970
Brief Title
Retina is a Marker for Cerebrovascular Heath
Official Title
Retinal Vasoreactivity is a Marker for Cerebral Small Vessel Disease Progression
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 9, 2021 (Actual)
Primary Completion Date
June 2026 (Anticipated)
Study Completion Date
June 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cerebral Small Vessel Diseases, Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy, Cerebral Microbleeding, Sporadic White Matter Disease
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cilostazol
Arm Type
Experimental
Arm Description
Cilostazol 100mg BID
Arm Title
No intervention
Arm Type
No Intervention
Intervention Type
Drug
Intervention Name(s)
Cilostazol
Intervention Description
Cilostazol 100mg BID
Primary Outcome Measure Information:
Title
white matter disease volume
Description
change in total white matter disease volume
Time Frame
1 year
Secondary Outcome Measure Information:
Title
cognition
Description
global Z-score and by cognitive domain
Time Frame
1 year
Title
stroke
Description
ischemic stroke or hemorrhagic stroke
Time Frame
1 year
Title
cerebrovasoreactivity
Description
change in blood oxygen level dependence (BOLD) per unit of end tidal PCO2 mmHg
Time Frame
1 year
Title
retinal vasoreactivity
Description
change in retinal vessel density pre/post CO2 challenge
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Meredith McDonald
Phone
904-953-4200
Email
mcdonald.meredith@mayo.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michelle P Lin, MD, MPH
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Meredith McDonald
Phone
904-953-4200
Email
mcdonald.meredith@mayo.edu
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials
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Retina is a Marker for Cerebrovascular Heath
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