Cilostazol for Cerebral Small Vessel Disease
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Mayo Clinic
Disqualifiers: Pregnant, Breastfeeding, MRI intolerance, others
No Placebo Group
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?This trial aims to test cilostazol, a medication that prevents blood clots and improves blood flow, in older adults with cerebral small vessel disease (SVD). The study will evaluate if cilostazol can slow the progression of SVD by improving blood flow and reducing inflammation. Participants will undergo various tests to measure changes in their condition over time.
Do I have to stop taking my current medications for the trial?
The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.
What data supports the effectiveness of the drug Cilostazol for cerebral small vessel disease?
Research suggests that Cilostazol, known for its antiplatelet and neurovascular protective effects, may help slow the progression of cerebral small vessel disease by reducing white matter changes in the brain. Additionally, its use in preventing stroke and improving blood flow in peripheral arterial disease indicates potential benefits for brain health.
12345How is the drug cilostazol unique for treating cerebral small vessel disease?
Cilostazol is unique because it is primarily used to prevent stroke recurrence by inhibiting platelet aggregation (clumping together of blood cells), which is different from other treatments that may focus on different mechanisms. However, it may have more side effects compared to other anti-platelet drugs.
678910Eligibility Criteria
This trial is for adults over 18 with cerebral small vessel disease (SVD) conditions like CADASIL or sporadic white matter diseases, and also includes healthy controls without SVD. It's not open to those under 18, pregnant or breastfeeding individuals, people who can't follow commands, or those unable to tolerate an MRI.Inclusion Criteria
I have been diagnosed with CADASIL, sporadic WMD, or lobar CMB.
I am 18 years old or older.
Exclusion Criteria
You cannot handle getting an MRI.
You are currently breastfeeding.
I am under 18 years old.
+2 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Baseline Assessment
Participants undergo OCTA retinal scan, MRI-BOLD brain scan, cognitive battery evaluation, and blood sample collection
1 day
1 visit (in-person)
Treatment
Participants receive cilostazol or no intervention and are monitored for SVD progression
12 months
Biweekly telephone visits for 3 months, then monthly
Follow-up
Participants are monitored for safety and effectiveness after treatment with a 12-month follow-up visit
1 day
1 visit (in-person)
Participant Groups
The study tests if cilostazol, a drug that prevents blood clots and widens blood vessels, can slow down the progression of SVD—a brain condition linked to stroke and dementia—and if changes in retina blood flow are indicators of SVD health.
2Treatment groups
Experimental Treatment
Active Control
Group I: CilostazolExperimental Treatment1 Intervention
Cilostazol 100mg BID
Group II: No interventionActive Control1 Intervention
Cilostazol is already approved in United States, European Union, Japan for the following indications:
🇺🇸 Approved in United States as Pletal for:
- Intermittent Claudication
🇪🇺 Approved in European Union as Pletal for:
- Intermittent Claudication
🇯🇵 Approved in Japan as Pletal for:
- Intermittent Claudication
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Mayo Clinic in FloridaJacksonville, FL
Mayo Clinic FloridaJacksonville, FL
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Who Is Running the Clinical Trial?
Mayo ClinicLead Sponsor
References
Efficacy and safety of cilostazol in decreasing progression of cerebral white matter hyperintensities-A randomized controlled trial. [2023]Cerebral small vessel disease (SVD) is an important cause of dementia that lacks effective treatment. We evaluated the efficacy and safety of cilostazol, an antiplatelet agent with potential neurovascular protective effects, in slowing the progression of white matter hyperintensities (WMHs) in stroke- and dementia-free subjects harboring confluent WMH on magnetic resonance imaging (MRI).
Type 3 phosphodiesterase inhibitors may be protective against cerebrovascular events in patients with claudication. [2018]The risk of cerebrovascular events in patients with mild to moderate peripheral vascular disease is significant. Cilostazol is a phosphodiesterase type 3 (PDE3) inhibitor that is effective in the treatment of symptoms of peripheral arterial occlusive disease. The method of action includes antithrombotic, vasodilatory, and antiproliferative effects.
Cilostazol for Secondary Prevention of Stroke and Cognitive Decline: Systematic Review and Meta-Analysis. [2021]Cilostazol, a phosphodiesterase 3' inhibitor, is used in Asia-Pacific countries for stroke prevention, but rarely used elsewhere. In addition to weak antiplatelet effects, it stabilizes endothelium, aids myelin repair and astrocyte-neuron energy transfer in laboratory models, effects that may be beneficial in preventing small vessel disease progression.
[Role of cilostazol in the sequential therapeutic spectrum of the peripheral arterial occlusion disease (PAOD)]. [2018]Cilostazol (Pletal(®), UCB Pharma, Monheim, Deutschland) has been successfully established since its inauguration on the German market in 2007, which is associated with a considerable distribution, in particular, in angiologic patients. However, vascularsurgical specifics in the use of Cilostazol are still lacking. The aim of this very compact short overview is (based on a selective literature search and own clinical experiences over the years) to characterize mechanism of action, use and expectable therapeutic effect of Cilostazol in the challenging management of exclusively vascularsurgcial patients with peripheral arterial occlusion disease (PAOD). Cilostazol inhibits phosphodiesterase 3 and platelet aggregation in a reversible manner with a dose-effect association, has vasodilating potential and a positive inotropic effect but provides a selective effect on the platelets, muscle and endothelial cells of the vascular wall via an intracellular increase of cAMP; in addition, there is an antiproliferative effect, it promotes neoangiogenesis, inhibits apoptosis and generation of endothelial adhesion molecules - taken together, it can be considered antiatherogenic ("anti-arterioscleroticum"). From a clinical point of view, Cilostazol is indicated in stage IIb of PAOD (Fontaine); its recommended dosage is 2x100 (reduced in case of moderate side effects, 2x50) mg with detectable prolongation of subjective (reported by the patient) and objective walking distance (but not in smokers [!]; ABI-based measurement of the effect not suitable) and partially with an improval of the quality of life (associated with a prolonged but steadily improving therapeutic effect from the 4th to the 6th week until the 6th to the 12th month). The profile of side effects is broad but mostly short-term and dominated by headache [~ 30 %] and diarrhoea [~ 15 %]). While Cilostazol not only plays a beneficial role in the setting to be used in the primary arteriosclerotic course of PAOD (called sequential therapeutic preoperative course), it appears also to provide great effect in case of a re-manifestation of claudication (approaching stage IIb according to Fontaine's classification) after previous image-guided interventional or vascularsurgical treatment (suitable conservative mid-term intermediate therapy), i) resulting in a flexible physician's tool of the angiologic and vascularsurgical setting of an outpatient clinic, and ii) which reduces significantly the number of re-interventions or prolonges the time interval(s) in between. This might finally be relevant in the perspective for an amputation-free survival.
Cilostazol and peripheral arterial disease. [2019]Peripheral arterial disease is both common and disabling. Contemporary management of peripheral arterial disease is multimodal, encompassing both medical and interventional treatments. Cilostazol (Pletal), a 2-oxoquinolone derivative, is currently licensed in the UK for the treatment of patients with intermittent claudication to improve their walking distance in the absence of tissue necrosis or rest pain. The therapeutic effects of cilostazol are thought to be mediated through antiplatelet, antiproliferative and vasodilatory activities. This review aims to provide an overview of the management of peripheral arterial disease focusing upon cilostazol pharmacotherapy.
Escalation regimen of cilostazol for acute brain infarction. [2019]Several reports have indicated that cilostazol is effective in the prevention of recurrence after cerebral infarction. However, cilostazol is inferior in tolerability for the adverse events than other anti-platelet agents. The goal of this study was to determine whether cilostazol escalation oral administration affects its tolerability.
A Phase II trial of paclitaxel and topotecan with filgrastim in patients with recurrent or refractory glioblastoma multiforme or anaplastic astrocytoma. [2018]Therapy for high-grade gliomas remains unsatisfactory. Paclitaxel and topotecan have separately demonstrated activity against gliomas. We conducted a Phase II trial of these agents in combination with filgrastim (G-CSF) in patients with recurrent or refractory glioblastoma multiforme or anaplastic astrocytoma.
Macitentan, a Dual Endothelin Receptor Antagonist, in Combination with Temozolomide Leads to Glioblastoma Regression and Long-term Survival in Mice. [2018]The objective of the study was to determine whether astrocytes and brain endothelial cells protect glioma cells from temozolomide through an endothelin-dependent signaling mechanism and to examine the therapeutic efficacy of the dual endothelin receptor antagonist, macitentan, in orthotopic models of human glioblastoma.
Local intracerebral administration of Paclitaxel with the paclimer delivery system: toxicity study in a canine model. [2018]Paclitaxel, a microtubule binding agent with potent anti-glioma activity in vitro, exhibits poor penetrance to the CNS when delivered systemically. To minimize toxicity and reach therapeutic concentrations in the CNS, paclitaxel was previously incorporated into biodegradable microspheres (Paclimer), and the efficacy of Paclimer was determined in a rat model of malignant glioma. In this study we report the safety of intracranial Paclimer in a canine dose escalation toxicity study to prepare its translation into clinical scenarios.
Irinotecan in the treatment of glioma patients: current and future studies of the North Central Cancer Treatment Group. [2018]Other than nitrosoureas (carmustine and lomustine) and temozolomide, no agents have consistently demonstrated clinically meaningful benefits for patients with gliomas. The active metabolite of irinotecan, 7-ethyl-10-hydroxy camptothecin (SN-38), exhibited promising antitumor effects in preclinical glioma models. Clinical trials using weekly or every 3 weeks dosing of irinotecan have been completed. Toxicity consisted primarily of mild to moderate neutropenia and diarrhea with both schedules, with occasional severe toxicity including one death from neutropenia and infection. Preliminary analyses have suggested imaging responses in 10-15% of patients. Preclinical models and our understanding of the mechanism of action suggest that irinotecan may sensitize glioma cells to the cytotoxic actions of radiation therapy and alkylating agents; clinical trials designed to assess the therapeutic benefit of combination therapy currently are in progress. There is substantial clinical evidence that the concurrent administration of irinotecan with certain anticonvulsants produces reduced exposure to SN-38. In the absence of anticonvulsants, there is also substantial interpatient variability in drug exposure, perhaps reflecting inherited differences in drug metabolism. Finally several mechanisms of tumor cell resistance to irinotecan have been hypothesized, but the clinical significance of these observations has not been confirmed. Correlative studies to address these pharmacokinetic, pharmacogenetic, and drug resistance questions are ongoing.