Cilostazol for Cerebral Small Vessel Disease

Recruiting at 1 trial location

Overseen By Meredith McDonald

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Mayo Clinic

Disqualifiers: Pregnant, Breastfeeding, MRI intolerance, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 12 months

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests cilostazol, a drug known for improving blood flow and reducing inflammation, to determine if it can slow the progression of cerebral small vessel disease (SVD). SVD affects tiny blood vessels in the brain, doubling the risk of stroke and significantly increasing the risk of dementia. The study aims to discover if changes in brain and eye blood vessels can serve as markers to track SVD progression. Suitable participants include those diagnosed with conditions like CADASIL, those with specific brain changes, or their healthy friends or family without SVD. As a Phase 1, Phase 2 trial, this research focuses on understanding cilostazol's effects in people and measuring its effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that cilostazol is likely to be safe for humans?

Research has shown that cilostazol is generally well-tolerated. Studies suggest it may improve blood flow in the brain and protect blood vessel walls, which is crucial for conditions like cerebral small vessel disease (SVD) that can lead to strokes or dementia.

In some studies, patients taking cilostazol experienced fewer strokes than those taking aspirin. Specifically, there were 0.5 stroke cases per 100 person-years with cilostazol, compared to 4.5 cases with aspirin, suggesting cilostazol might reduce stroke risk more safely.

Another study found that cilostazol did not worsen the brain's white matter over time, indicating a positive safety profile. While it didn’t completely halt changes, it didn’t exacerbate them either.

Overall, cilostazol appears promising for safety, especially for those with SVD. However, joining a clinical trial is a personal decision and should be discussed with a doctor. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for cerebral small vessel disease?

Unlike the standard treatments for cerebral small vessel disease, which often focus on managing symptoms and reducing stroke risk through blood pressure and cholesterol control, Cilostazol offers a different approach. Cilostazol is unique because it works by inhibiting phosphodiesterase-3, leading to increased blood flow and improving vascular health. Researchers are excited about Cilostazol because it not only addresses the symptoms but also targets the underlying vascular issues, potentially offering a more comprehensive treatment strategy. This mechanism could provide better outcomes for patients by improving blood vessel function and reducing the risk of further complications.

What evidence suggests that cilostazol might be an effective treatment for cerebral small vessel disease?

Studies have shown that cilostazol might improve brain function in people with cerebral small vessel disease (SVD). It lowers the risk of ischemic vascular events, which are problems with blood flow in the brain. Cilostazol may also enhance blood flow and protect blood vessel walls, potentially benefiting those with SVD. However, some research found that cilostazol did not alter SVD progression over a year, both in symptoms and brain scans. While cilostazol has shown promising effects, results remain mixed, necessitating further research. Participants in this trial will receive either cilostazol or no intervention to further evaluate its effects on SVD. ^{1 2 4 6 7}

Who Is on the Research Team?

Michelle P Lin, MD, MPH

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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.

Exclusion Criteria

You cannot handle getting an MRI.

You are currently breastfeeding.

I am under 18 years old.

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• Cilostazol

Trial Overview

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.

How Is the Trial Designed?

Group I: Cilostazol Experimental Treatment 1 Intervention

Cilostazol 100mg BID

Group II: No intervention Active Control 1 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

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

Cilostazol is an effective treatment for patients with peripheral arterial disease, specifically for improving walking distance in those suffering from intermittent claudication, without tissue necrosis or rest pain.

The drug works through multiple mechanisms, including antiplatelet, antiproliferative, and vasodilatory effects, making it a valuable option in the multimodal management of peripheral arterial disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cilostazol and peripheral arterial disease. Pearce, L., Ghosh, J., Counsell, A., et al.[2019]

In a study of 1435 patients with mild to moderate peripheral arterial occlusive disease, the overall rate of cerebrovascular events was 4.6% over a mean follow-up of 515 days, indicating a significant risk in this population.

Patients treated with cilostazol, a PDE3 inhibitor, had a lower incidence of cerebrovascular events (3.2%) compared to those on placebo (6.1%), suggesting that cilostazol may help reduce the risk of such events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Type 3 phosphodiesterase inhibitors may be protective against cerebrovascular events in patients with claudication. Stone, WM., Demaerschalk, BM., Fowl, RJ., et al.[2018]

In a study of 168 patients with brain infarction, an escalation regimen of cilostazol (starting at 50 mg b.i.d. for 4 days, then 100 mg b.i.d.) resulted in better tolerability compared to the standard regimen of 100 mg b.i.d. from the start.

The escalation group had significantly fewer patients discontinuing treatment and a lower incidence of headaches, suggesting that this dosing strategy may enhance patient adherence and comfort during cilostazol therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Escalation regimen of cilostazol for acute brain infarction. Nishiyama, K., Seyama, H., Okano, H., et al.[2019]

Irinotecan, particularly its active metabolite SN-38, shows promising antitumor effects in glioma models, with preliminary clinical trials indicating imaging responses in 10-15% of patients, despite some associated toxicities like neutropenia and diarrhea.

The drug may enhance the effectiveness of radiation therapy and alkylating agents against glioma cells, but its clinical benefits are still being evaluated in ongoing trials, especially considering factors like drug exposure variability and potential resistance mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan in the treatment of glioma patients: current and future studies of the North Central Cancer Treatment Group. Buckner, JC., Reid, JM., Wright, K., et al.[2018]

In a study involving 12 beagle dogs, the delivery of paclitaxel via biodegradable microspheres (Paclimer) showed minimal systemic and central nervous system (CNS) toxicity, indicating a safe method for intracranial administration.

Dogs treated with Paclimer exhibited normal behavior and weight gain, with no signs of neurological toxicity or significant adverse effects, suggesting that this delivery method could be a promising approach for treating gliomas in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local intracerebral administration of Paclitaxel with the paclimer delivery system: toxicity study in a canine model. Pradilla, G., Wang, PP., Gabikian, P., et al.[2018]

In a 2-year study involving 120 stroke- and dementia-free participants with white matter hyperintensities (WMHs), cilostazol did not significantly slow the progression of WMH volume compared to placebo.

Cilostazol was found to have an acceptable safety profile, with no significant differences in bleeding or vascular events between the cilostazol and placebo groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of cilostazol in decreasing progression of cerebral white matter hyperintensities-A randomized controlled trial. Ip, BYM., Lam, BYK., Hui, VMH., et al.[2023]

Cilostazol is effective in treating patients with stage IIb peripheral arterial occlusive disease (PAOD) by improving walking distance and quality of life, with a recommended dosage of 100 mg twice daily, showing benefits from 4 to 12 weeks of treatment.

The drug works by inhibiting phosphodiesterase 3, leading to vasodilation and reduced platelet aggregation, while also promoting neoangiogenesis and having antiatherogenic effects, making it a valuable option in both preoperative and postoperative management of PAOD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Role of cilostazol in the sequential therapeutic spectrum of the peripheral arterial occlusion disease (PAOD)]. Weber, T., Meyer, F., Weber, M., et al.[2018]

The dual endothelin receptor antagonist macitentan effectively counteracts the protective effects of astrocytes and brain endothelial cells on glioma cells, enhancing the efficacy of temozolomide in treating glioblastoma.

In a study involving nude mice with glioblastomas, 96% of those treated with macitentan and temozolomide showed no evidence of disease, indicating a strong therapeutic potential for this combination in overcoming drug resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Macitentan, a Dual Endothelin Receptor Antagonist, in Combination with Temozolomide Leads to Glioblastoma Regression and Long-term Survival in Mice. Kim, SJ., Lee, HJ., Kim, MS., et al.[2018]

In a Phase II trial involving 20 patients with recurrent glioblastoma or anaplastic astrocytoma, the combination of paclitaxel and topotecan showed modest efficacy, with 12% of patients achieving partial remission and 41% experiencing stable disease.

Despite some therapeutic benefits, the treatment caused significant hematologic toxicity, with 25% of patients suffering from severe leukopenia, leading to two deaths from infections and the conclusion that this combination therapy is not justifiable for further study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II trial of paclitaxel and topotecan with filgrastim in patients with recurrent or refractory glioblastoma multiforme or anaplastic astrocytoma. Pipas, JM., Meyer, LP., Rhodes, CH., et al.[2018]

Cilostazol significantly reduces the risk of recurrent ischemic stroke (by 32%) and hemorrhagic stroke (by 57%) based on a systematic review of 20 randomized controlled trials involving over 10,500 participants, primarily from Asia-Pacific countries.

The drug is effective for long-term secondary stroke prevention without increasing the risk of hemorrhage, but it may cause side effects like headaches and palpitations, indicating a need for further studies in Western populations to evaluate its broader efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cilostazol for Secondary Prevention of Stroke and Cognitive Decline: Systematic Review and Meta-Analysis. McHutchison, C., Blair, GW., Appleton, JP., et al.[2021]

Citations

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Cilostazol reduced recurrent ischemic stroke more when given long (>6 months) versus short term without increasing hemorrhage, and in trials ...

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ejnpn.springeropen.com

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Clinical and radiological outcome of incidental cerebral small ...

This study found that neither aspirin nor cilostazol had an impact on clinical and radiological progression over 1 year in patients with CSVD.

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jamanetwork.com

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Isosorbide Mononitrate and Cilostazol Treatment in ...

This randomized clinical trial examines treatment outcomes with isosorbide mononitrate and cilostazol in patients with symptomatic cerebral ...

7.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/36583111/

Efficacy and safety of cilostazol in decreasing progression ...

In this trial with stroke- and dementia-free subjects with confluent WMHs, cilostazol did not impact WMH progression but demonstrated an ...