Cilostazol for Cerebral Small Vessel Disease
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Mayo Clinic
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.
Is the drug Cilostazol a promising treatment for Cerebral Small Vessel Disease?Cilostazol is considered promising because it has been shown to help prevent the recurrence of cerebral infarction, which is a type of stroke. This suggests it could be beneficial for treating Cerebral Small Vessel Disease.4561012
What safety data exists for Cilostazol in treating cerebral small vessel disease?The provided research does not contain safety data for Cilostazol or its other names. It focuses on the safety profiles of Taxol (Paclitaxel) and Docetaxel, which are unrelated to Cilostazol. For Cilostazol, you would need to look at studies specifically evaluating its safety and efficacy in treating cerebral small vessel disease.12369
Do I need to stop my current medications to join the trial?The trial protocol does not specify whether you need to stop your current medications.
What data supports the idea that the drug Cilostazol for Cerebral Small Vessel Disease is an effective treatment?The available research shows that Cilostazol may help slow the progression of cerebral small vessel disease by reducing the worsening of white matter changes in the brain, which are linked to dementia. This suggests that Cilostazol could be effective in managing this condition. Additionally, Cilostazol is used in other conditions like stroke prevention and peripheral arterial disease, where it helps improve blood flow and reduce symptoms, indicating its potential benefits for cerebral small vessel disease as well.78111314
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 am 18 years old or older.
Exclusion Criteria
I am under 18 years old.
I cannot follow instructions.
Treatment Details
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
Overview of Taxol safety. [2015]The safety profile of Taxol administered intravenously as a single agent has been established based on the experience of 655 patients. Of these patients, 253 were treated in nine phase I studies, and 402 were treated in eight disease-oriented phase II studies. Myelosuppression, specifically neutropenia, was the dose-limiting toxicity in all studies conducted in patients with solid tumors. Neutropenia was schedule dependent and was less severe when Taxol was administered via a 3-hour infusion. Severe hypersensitivity reactions were controlled in the phase II program with a premedication regimen consisting of dexamethasone, an antihistamine, and an H2 blocker. Cardiovascular toxicities were minimal and do not indicate constant electrocardiographic monitoring during Taxol infusions. Peripheral neuropathy was usually mild to moderate and dose related; however, it rarely caused treatment discontinuation. Additional adverse events associated with Taxol include arthralgia/myalgia, mucositis, nausea and vomiting, and alopecia.
The taxoids: paclitaxel (Taxol) and docetaxel (Taxotere). [2019]The taxoids, paclitaxel (Taxol) and docetaxel (Taxotere), represent a novel class of antineoplastic drugs. Paclitaxel and docetaxel share a similar mechanism of action: the promotion of microtubule assembly and inhibition of microtubule disassembly. The clinical development of paclitaxel was initially hampered by hypersensitivity reactions (HSRs). The use of premedications and prolongation of the infusion time to 24h has reduced these reactions and allowed this drug's clinical development. Although paclitaxel's clinical activity has not been fully investigated, clinical trials have demonstrated its activity against ovarian, breast, and bronchial carcinomas. Because phase I studies of docetaxel noted occasional HSRs and these observations increased with further clinical experiences, those premedications employed with paclitaxel have now been instituted in many phase II studies of docetaxel. Docetaxel is currently being investigated in ovarian, breast, and bronchial carcinomas and has shown impressive clinical activity. The dose-limiting toxicity of both these agents is neutropenia; myalgias, mucositis, neuropathies, and alopecia have also been observed with both drugs. Additionally, a fluid retention syndrome and cutaneous toxicities have been noted in patients treated with docetaxel. Future studies of the taxoids will allow further comparisons of the toxicity and efficacy of these agents.
A phase I dose-escalation study of docetaxel with granulocyte colony-stimulating factor support in patients with solid tumours. [2020]Docetaxel is a widely active cytotoxic agent. The principal dose-limiting toxicities (DLTs) of the 3-weekly regimen are neutropenia and febrile neutropenia. Use of prophylactic granulocyte colony-stimulating factor (G-CSF) may allow higher doses of docetaxel to be administered with potentially greater anticancer efficacy. The objectives of this study were to determine the maximum tolerated dose (MTD) and toxicity profile of docetaxel given with G-CSF support.
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.
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.
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.
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 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.
Delayed seizure associated with paclitaxel-Cremophor el in a patient with early-stage breast cancer. [2015]Paclitaxel, a microtubule stabilizer, is an effective agent for treating cancer of the breast, ovary, head and neck, and lung. Because paclitaxel is insoluble in water, it is formulated with the micelle-forming Cremophor EL. Neurologic toxicity is well described with both the drug and this carrier, with most toxicities manifesting as peripheral neuropathy, motor neuropathy, autonomic neuropathy, and myopathy. Toxic effects on the central nervous system, such as seizures or encephalopathy, have been rarely reported; however, the seizures reported were closely related to the time of infusion. We describe a 41-year-old woman with no history of seizures who was treated with paclitaxel for breast cancer. Four days after the drug was infused, she developed a generalized tonic-clonic seizure that could not be attributed to other causes. The patient was treated with phenytoin and was able to complete her adjuvant chemotherapy with nab-paclitaxel without further events. Her condition was neurologically stable without phenytoin for the next 6 months. Use of the Naranjo adverse drug reaction probability scale indicated a possible association (score of 3) between the delayed seizure and paclitaxel or its solvent, Cremophor EL. Clinicians should be aware of the potential for seizure activity in patients who receive paclitaxel formulated with Cremophor EL.
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.
[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.
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.
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.
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).