Cilostazol for Cerebral Small Vessel Disease

Recruiting at 1 trial location

Overseen By Meredith McDonald

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. ^{1 2 3 4 5}

How 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. ^{6 7 8 9 10}

Research Team

Michelle P Lin, MD, MPH

Principal Investigator

Mayo Clinic

Eligibility 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.

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)

Treatment Details

Interventions

• Cilostazol (Antiplatelet Agent)

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.

Participant Groups

Group I: Cilostazol Experimental Treatment 1 Intervention

Cilostazol 100mg BID

Group II: No intervention Active Control 1 Intervention

Cilostazol is already approved in Japan for the following indications:

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+

Findings from Research

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]

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]

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]

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 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]

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]

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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of cilostazol in decreasing progression of cerebral white matter hyperintensities-A randomized controlled trial. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Type 3 phosphodiesterase inhibitors may be protective against cerebrovascular events in patients with claudication. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Cilostazol for Secondary Prevention of Stroke and Cognitive Decline: Systematic Review and Meta-Analysis. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

[Role of cilostazol in the sequential therapeutic spectrum of the peripheral arterial occlusion disease (PAOD)]. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Cilostazol and peripheral arterial disease. [2019]

6. Japan pubmed.ncbi.nlm.nih.gov

Escalation regimen of cilostazol for acute brain infarction. [2019]

7. United States 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. [2018]

8. United States 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. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Local intracerebral administration of Paclitaxel with the paclimer delivery system: toxicity study in a canine model. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Irinotecan in the treatment of glioma patients: current and future studies of the North Central Cancer Treatment Group. [2018]