Verapamil for Stroke

Recruiting at 4 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Global Neurosciences Institute

Disqualifiers: Pregnancy, Hepatic insufficiency, Renal insufficiency, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Immediate post-thrombectomy

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to aid recovery from acute ischemic stroke using a medicine called verapamil. The focus is on delivering verapamil directly into the arteries (intra-arterial delivery) to assess its safety and effectiveness in stroke recovery. Participants who have undergone mechanical thrombectomy (a procedure to remove a blood clot) and experienced stroke symptoms for less than 8 hours might be suitable candidates. The trial will test two doses of verapamil, 10 mg and 20 mg, to determine which is most effective. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking advancements in stroke recovery.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that delivering verapamil directly into the arteries is safe for treating strokes. Studies have found that patients tolerate this method well, without serious side effects such as bleeding or increased risk of death. Verapamil is already commonly used to treat spasms in brain blood vessels.

Specifically, using verapamil immediately after a procedure to remove a blood clot, known as a thrombectomy, proved to be safe. Patients who received this treatment did not experience major complications, making it a promising option for stroke recovery. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike current treatments for ischemic stroke, which often involve clot-busting drugs like alteplase or surgery like mechanical thrombectomy, Verapamil is delivered directly into the arteries. This unique intra-arterial delivery method allows for targeted, localized treatment right at the site of the stroke. Researchers are excited about Verapamil because it could enhance blood flow in the brain after a stroke by relaxing blood vessels, potentially reducing brain damage more effectively than existing options. Additionally, the study investigates two different doses (10 mg and 20 mg), which could provide insights into the most effective dosage for maximizing recovery.

What evidence suggests that intra-arterial delivery of Verapamil might be an effective treatment for acute ischemic stroke?

Research shows that delivering verapamil directly into the arteries may help treat sudden strokes caused by blocked blood flow. Studies on mice have found that this drug relaxes blood vessels, protecting brain cells and aiding recovery after a stroke. Verapamil is considered safe and can protect nerve cells from damage post-stroke. In experiments, it reduced the size of brain damage and improved recovery after thrombectomy, a procedure that removes blood clots. In this trial, ischemic stroke patients with large penumbra will be randomly assigned to receive either a 10 mg or 20 mg dose of verapamil following mechanical thrombectomy. These findings suggest that using verapamil in this way may enhance stroke recovery. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with acute ischemic stroke who can live at least 3 more months. They must have had a mechanical thrombectomy, be able to consent in writing, and commit to rehab therapy. Excluded are pregnant women, those with severe liver/kidney issues or low platelets, prior disability, or intolerance to verapamil.

Inclusion Criteria

I am willing to attend rehabilitation therapy sessions.

Written informed consent

I recently had symptoms or a CT scan showing a stroke.

Exclusion Criteria

Thrombocytopenia (platelet count <75,000/mm3)

You have had a bad reaction to verapamil in the past.

I have had a severe stroke.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intra-arterial delivery of Verapamil following mechanical thrombectomy

Immediate post-thrombectomy

Follow-up

Participants are monitored for safety and effectiveness after treatment, including neuroimaging and functional outcomes

12 months

Multiple visits for neuroimaging and assessments

What Are the Treatments Tested in This Trial?

Interventions

• Intra-arterial delivery of Verapamil

Trial Overview The study tests intra-arterial delivery of verapamil (at doses of 10 mg or 20 mg) in patients after an acute ischemic stroke. It aims to determine the safety of this method and its impact on recovery when administered post-mechanical thrombectomy.

How Is the Trial Designed?

Group I: Verapamil 20 mg Treatment Group Experimental Treatment 1 Intervention

Ischemic stroke patients with large penumbra are offered Verapamil treatment following mechanical thrombectomy. The patient will be randomly assigned an intervention group with the specified dose (20 mg) Verapamil.

Group II: Verapamil 10 mg Treatment Group Experimental Treatment 1 Intervention

Ischemic stroke patients with large penumbra are offered Verapamil treatment following mechanical thrombectomy. The patient will be randomly assigned an intervention group with the specified dose (10 mg) Verapamil.

Who Is Running the Clinical Trial?

Global Neurosciences Institute

Lead Sponsor

Trials

3

Recruited

140+

Published Research Related to This Trial

Intra-arterial administration of verapamil after recanalization in a mouse model of ischemic stroke significantly reduced brain damage and improved recovery, showing its potential as a neuroprotective therapy.

The treatment was well tolerated with no observed side effects or increased mortality, indicating that verapamil could be a safe adjunct therapy to thrombectomy in stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stroke neuroprotection revisited: Intra-arterial verapamil is profoundly neuroprotective in experimental acute ischemic stroke. Maniskas, ME., Roberts, JM., Aron, I., et al.[2018]

Intravenous verapamil effectively reversed hemiplegia in a 31-year-old woman suffering from a migraine, as indicated by a decrease in middle cerebral artery flow velocity measured by transcranial Doppler.

This case suggests that verapamil may be a potential treatment for intractable migraines associated with vasospasm of major cerebral arteries, although further research is needed to confirm the relationship between hemodynamic changes and clinical improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of intravenous verapamil on cerebral hemodynamics in a migraine patient with hemiplegia. Ng, TM., Kohli, A., Fagan, SC., et al.[2017]

In a double-blind, placebo-controlled trial involving 164 patients with acute ischemic stroke, nimodipine did not significantly reduce mortality or improve neurologic outcomes for the overall group after 28 days.

However, in a subgroup of patients who were more severely affected (Mathew Scale score of 65 or less at baseline), those treated with nimodipine showed a significantly better neurologic outcome, indicating that nimodipine may be beneficial for certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo-controlled trial of nimodipine in the treatment of acute ischemic cerebral infarction. Martínez-Vila, E., Guillén, F., Villanueva, JA., et al.[2019]

Intraarterial administration of verapamil effectively resolved vasospasm in all four patients who experienced significant neurological deficits after surgery for intracranial tumors, as confirmed by angiographic data.

While the treatment successfully alleviated vasospasm, the clinical outcomes varied; two patients achieved almost full recovery, while the other two avoided lethal outcomes despite not experiencing significant clinical improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of postoperative vasospasm with intraarterial verapamil after removal of intracranial tumor: patient series. Mikeladze, K., Konovalov, A., Bykanov, A., et al.[2022]

In a study of 42 patients who underwent surgery for cerebral aneurysms, prolonged intracisternal infusion (PII) of verapamil was found to be safe, with only 2.4% developing new ischemic foci and no infectious complications reported.

The initial results suggest that PII may effectively prevent cerebral vasospasm (CVS) after subarachnoid hemorrhage, especially when combined with intra-arterial verapamil, but further research is needed to fully assess its efficacy compared to other treatment methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Intracisternal administration of verapamil for the prevention and treatment of vasospasm in patients after microsurgical treatment of cerebral aneurysms in the acute period of hemorrhage]. Pilipenko, YV., Varyukhina, MD., Eliava, SS., et al.[2019]

Intra-arterial verapamil infusion is a common treatment for vasospasm following aneurysmal subarachnoid hemorrhage (aSAH), but it can lead to rare complications such as seizures, as demonstrated in a case involving a 24-year-old woman.

Despite the occurrence of seizures during verapamil infusion, the treatment effectively resolved the patient's expressive aphasia and highlights the need for awareness of seizure risks when using this therapy for refractory vasospasm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intra-arterial verapamil-induced seizures: case report and review of the literature. Westhout, FD., Nwagwu, CI.[2013]

Supplementing endovascular thrombectomy with intra-arterial (IA) verapamil is safe and feasible, as shown in the Phase I SAVER-I trial, which indicated no increased risk of complications in human subjects.

Verapamil demonstrated a dose-response relationship that effectively prevented neuron death and ischemic damage in pre-clinical models, suggesting it could enhance recovery after large vessel ischemic stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intra-arterial verapamil post-thrombectomy is feasible, safe, and neuroprotective in stroke. Fraser, JF., Maniskas, M., Trout, A., et al.[2018]

Intra-arterial administration of the calcium channel blocker verapamil effectively reversed flow-limiting vasospasm in the common carotid artery of a baboon, resulting in a 21% increase in vessel diameter and a 46.7% increase in cross-sectional area after treatment.

This study suggests that verapamil could be a promising endovascular treatment for vasospasm in medium to large vessels, with no significant changes in systemic blood pressure observed during the procedure, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of mechanically-induced vasospasm of the carotid artery in a primate using intra-arterial verapamil: a technical case report. Coon, AL., Colby, GP., Mack, WJ., et al.[2018]

Citations

1. withpower.com withpower.com/trial/phase-1-ischemic-stroke-3-2017-050a5

Verapamil for Stroke · Recruiting Participants for Phase ... Research on mice shows that intra-arterial verapamil, a drug that helps relax blood vessels, can protect brain cells and improve recovery after a stroke. This ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26661189/

Stroke neuroprotection revisited: Intra-arterial verapamil is ... Verapamil administered intra-arterially immediately following recanalization in experimental ischemic stroke is both safe and neuroprotective.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10134451/

Intra-arterial verapamil improves functional outcomes of ... The present study aims to answer if verapamil exerts direct neuroprotective effects and alleviates glucose toxicity following thrombectomy in a preclinical ...

4. journals.sagepub.com journals.sagepub.com/doi/10.1177/0271678X15608395

Stroke neuroprotection revisited: Intra-arterial verapamil is ... Verapamil administered intra-arterially immediately following recanalization in experimental ischemic stroke is both safe and neuroprotective and merits ...

5. mdpi.com mdpi.com/1422-0067/25/2/891

Neuroprotection during Thrombectomy for Acute Ischemic ... In mouse models, administration of intra-arterial verapamil following recanalization of middle cerebral artery occlusion reduced infarct volume, improved ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5669346/

Intra-arterial verapamil post-thrombectomy is feasible, safe ... We conclude that superselective IA verapamil administration immediately following thrombectomy is safe and feasible, and has direct, dose–response-related ...

7. journals.lww.com journals.lww.com/neurosurgery/abstract/2024/04001/391_intraarterial_verapamil_for_neuroprotection_in.299.aspx

391 Intraarterial Verapamil for Neuroprotection in Ischemic ... This study suggests that verapamil is a safe and effective neuroprotective drug in ischemic stroke clinical populations that require mechanical thrombectomy ...

8. pure.johnshopkins.edu pure.johnshopkins.edu/en/publications/the-clinical-impact-and-safety-profile-of-high-dose-intra-arteria

The clinical impact and safety profile of high-dose intra ... The safety profile of high dose IA verapamil was a secondary endpoint. Results: IA verapamil was delivered between 2–16 days after ictus (median post-bleed day ...

9. scholars.uky.edu scholars.uky.edu/en/publications/stroke-neuroprotection-revisited-intra-arterial-verapamil-is-prof

Stroke neuroprotection revisited: Intra-arterial verapamil is ... Furthermore, intra-arterial administration of verapamil was well tolerated with no hemorrhage, systemic side effects, or increased mortality. Thus, verapamil ...