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

Trial Summary

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.

What data supports the effectiveness of the drug verapamil for stroke treatment?

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 method of delivering verapamil directly to the brain was found to be safe and effective in reducing brain damage and improving outcomes. ^{1 2 3 4 5}

Is intra-arterial verapamil safe for use in humans?

Research shows that intra-arterial verapamil is generally safe in humans, with studies indicating no increased risk of bleeding or other serious side effects when used for stroke and vasospasm treatment. ^{1 3 4 6 7}

How is the drug verapamil used in stroke treatment unique?

Intra-arterial delivery of verapamil for stroke is unique because it directly targets the affected brain area, minimizing systemic side effects and providing neuroprotection by reducing brain damage and improving recovery after a stroke. ^{1 2 3 4 8}

What is the purpose of this trial?

The purpose of this research study is to test an experimental procedure called intra-arterial delivery of verapamil in patients diagnosed with acute ischemic stroke. This study investigates the safety of intra-arterial delivery of verapamil, a drug used to treat vasospasm (spasm of a blood vessel), and how it affects recovery from stroke. Recruitment is limited to patients that have received mechanical thrombectomy as standard of care.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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]

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]

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]

References

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

Stroke neuroprotection revisited: Intra-arterial verapamil is profoundly neuroprotective in experimental acute ischemic stroke. [2018]

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

The effect of intravenous verapamil on cerebral hemodynamics in a migraine patient with hemiplegia. [2017]

3. Russia (Federation) 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]. [2019]

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

Treatment of postoperative vasospasm with intraarterial verapamil after removal of intracranial tumor: patient series. [2022]

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

Placebo-controlled trial of nimodipine in the treatment of acute ischemic cerebral infarction. [2019]

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

Intra-arterial verapamil post-thrombectomy is feasible, safe, and neuroprotective in stroke. [2018]

7. England 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. [2018]

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

Intra-arterial verapamil-induced seizures: case report and review of the literature. [2013]