Superselective Citicoline and Verapamil for Ischemic Neuroprotection and Greater Effective Response

NCT ID: NCT02823106

Last Updated: 2016-09-23

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-31
• Study Completion Date: 2016-09-30

Brief Summary

This is a phase 1, blinded-outcome, randomized, placebo controlled study to investigate the safety and feasibility of super-selective intra-arterial administration of verapamil and citicoline immediately following successful endovascular thrombectomy as a potential neuroprotective synergistic therapeutic strategy in emergent large vessel occlusion stroke. This trial represents the first time that citicoline will be evaluated in human subjects as a superselectively administered neuroprotective agent administered in an acute time frame as an adjunct to intra-arterial thrombectomy. Furthermore, it will represent the first trial to evaluate combinational therapy for acute stroke neuroprotection.

Detailed Description

Participants will be recruited from patients evaluated at University of Kentucky Chandler Hospital for acute ischemic stroke. Participants with impaired capacity may be included, as the pathology to be studied (stroke) may impair their capacity. Initial contact will be made by the sub-investigators approved to obtain consent; all sub-investigators are practitioners who would make contact with potential participants in a clinical manner under standard clinical procedures. All sub-investigators will have access to stroke patients' medical information under normal circumstances. No special outreach is necessary to recruit particular populations. Enrollment goal will be 15 patients in each group.

Participants will not be compensated or provided any incentives for study participation.

The following describes all study procedures and evaluations that are to be done as part of the study.

Visit 1-Baseline (Day 0):

• Obtain consent.
• Medical history taken from medical record, participant and family to determine eligibility based on inclusion/exclusion criteria (Standard of Care)
• Medication history (Standard of Care)
• Physical examination to include vital signs (Standard of Care)
• Pregnancy Testing (Standard of Care)
• NIH Stroke Scale (Standard of Care)
• Verify inclusion/exclusion criteria
• Randomization
• Cerebral angiogram with Endovascular Thrombectomy (Standard of Care)
• Study Drug administration
• Adverse event (AE) collection

Visit 2 - Within 48 hours of admission

• Non-contrast Postoperative MRI or CT (Standard of Care) The choice of one or the other will be determined by clinical criteria; CT or MRI may be preferable for different reasons depending upon the patient's clinical scenario.

Visit 3 - ( By Discharge)

• NIH Stroke Scale (Standard of Care)
• Discharge Destination (Standard of Care)
• Cognitive Assessment (Standard of Care)
• Radiographic assessment of primary and secondary radiologic endpoints

Visit 4 - End of Study (90 Days) (+/- 30 days)

• UBACC assessment will be used to assess consent capacity at follow-up.
• Montreal Cognitive Assessment (MoCA)
• Modified Rankin Score (mRS; Standard of Care)

The visit may be conducted over the phone with the participant or their legally authorized representative.

Unscheduled Visits. It is unexpected that Unscheduled Visits will be common, especially with the follow-up within 90 days after the procedure. However, subjects readmitted to the hospital for any reason will be tracked to determine if an AE occurred.

There are no particular prohibited medications, treatments, or procedures for after administration of the study drug. However, therapeutic anticoagulation is a relative contraindication to thrombectomy. Patients on therapeutic anticoagulation will be excluded from the study.

Following successful completion of the baseline visit, participants will be randomized into the study. The randomization number will be assigned by the PI/neurointerventionalist.

Participants will be randomized to receive 10mg of verapamil in 10 cc of normal saline and 1000mg of citicoline in 10cc of normal saline or matching placebo.

Conditions

Ischemic Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Verapamil and Citicoline

10mg of verapamil in 10 cc of normal saline and 1000mg of citicoline in 10cc of normal saline will be administered over 20 minutes (1cc/minute) through the microcatheter and into the vessel previously obstructed by clot to the treatment group

Group Type: EXPERIMENTAL

Verapamil and Citicoline

Intervention Type: DRUG

Single dosing strategy will be used.

Placebo

The control group will receive saline only.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Single matching dosing strategy will be used.

Interventions

Verapamil and Citicoline

Single dosing strategy will be used.

Intervention Type: DRUG

Placebo

Single matching dosing strategy will be used.

Intervention Type: OTHER

Other Intervention Names

CDP-choline; 0.9% sodium chloride

Eligibility Criteria

Inclusion Criteria

• Signed and dated informed consent and HIPAA form. Participants with impaired capacity may be included provided a Legally Authorized Representative as recognized by the the State of Kentucky, signs the informed consent.
• Willingness to comply with all study procedures and availability for the duration of the study.
• Male or female, aged 18 years or older
• Suspected acute ischemic stroke based on clinical and radiographic evidence as determined and documented by the Stroke Neurology team at University of Kentucky.
• Participants must meet criteria for intra-arterial thrombectomy as determined and documented by Interventional Neuroradiology attending physician at University of Kentucky.
• Participants must have an acute thromboembolus within an intracranial artery in the anterior circulation (internal carotid, anterior cerebral, middle cerebral), which undergoes mechanical thrombectomy.
• Participant must have a TICI 2B or better revascularization via thrombectomy.
• For females of reproductive potential a negative pregnancy test at baseline is required. .

Exclusion Criteria

• Pregnant/lactating women
• Therapeutic anticoagulation prior to admission as it is a relative contraindication to thrombectomy
• Participants who undergo intra-arterial thrombectomy for acute stroke, in whom only TICI 0-2A revascularization is obtained.
• Known allergic reactions to components of Verapamil or Citicoline.
• Verapamil should not be given to individuals who have a serious heart condition such as:
• sick sinus syndrome or AV block
• severe heart failure;
• fainting do to slow heartbeats
• certain heart rhythm disorders of the atrium (excluding atrial fibrillation)
• active congestive heart failure;
• low blood pressure;
• a nerve-muscle disorder such as myasthenia gravis or muscular dystrophy.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 101 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Justin Fraser

OTHER

Sponsor Role: lead

Responsible Party

Justin Fraser

Sponsor/PI

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Justin Fraswer, MD

Role: PRINCIPAL_INVESTIGATOR

University of Kentucky

Locations

University of Kentucky Medical Center

Lexington, Kentucky, United States

Countries

United States

Other Identifiers

Citicoline and Verapamil

Identifier Type: -

Identifier Source: org_study_id