Clinical trial NCT04753970: Retina is a Marker for Cerebrovascular Heath
Official title: Retinal Vasoreactivity is a Marker for Cerebral Small Vessel Disease Progression
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Cerebral Small Vessel Diseases
Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy
Cerebral Microbleeding
Sporadic White Matter Disease
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2021-02-15
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).

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

Primary outcomes:
measure: white matter disease volume
timeFrame: 1 year
Secondary outcomes:
measure: cognition
timeFrame: 1 year
measure: stroke
timeFrame: 1 year
measure: cerebrovasoreactivity
timeFrame: 1 year
measure: retinal vasoreactivity
timeFrame: 1 year
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
Study officials:
affiliation: Mayo Clinic
name: Michelle P Lin, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: