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RCVS: The Rational Approach to Diagnosis and Treatment

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ClinicalTrials.gov Identifier: NCT03150524
Recruitment Status : Recruiting
First Posted : May 12, 2017
Last Update Posted : August 23, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
This is a randomized clinical trial of short-acting nimodipine versus twice daily extended release verapamil to treat patients presenting with Reversible Cerebral Vasoconstriction Syndrome (RCVS).

Condition or disease Intervention/treatment Phase
Reversible Cerebral Vasoconstriction Syndrome Diagnostic Test: TCD- cerebral blood flow velocities Behavioral: Headache pain score Other: Neurological examination Diagnostic Test: Repeat Neuroimaging Drug: Nimodipine Drug: Verapamil ER Phase 4

Detailed Description:
Patients greater than 18 years of age presenting with clinical signs and symptoms consistent with RCVS (see inclusion criteria) will be enrolled. Neuroimaging (CT, Magnetic Resonance (MR), or 4 vessel angiogram) will be obtained along with a baseline transcranial doppler ultrasound (TCD). They will subsequently be randomized to receive nimodipine (every 4 hours) or extended release verapamil (twice daily). Mean cerebral blood flow velocities will be followed for reduction or normalization on daily TCD and medication dosing adjusted appropriately. Patients will be followed 90 days post-discharge at which time they will undergo repeat neuroimaging to confirm resolution of vascular abnormalities and repeat evaluation. To determine effectiveness, the investigators will evaluate both short-term (surrogate) in-hospital outcomes and long-term outcomes. Reduction of TCD velocities and headache severity will serve as our short-term surrogate outcomes; however, need for additional medications, blood pressure, new/recurrent stroke/Intracranial Hemorrhage (ICH) will also be evaluated along with modified Rankin score (mRS) on discharge, length of stay, and discharge disposition. At 90 days, the investigators will also assess headache control along with mRS.. Adverse events and their relation to the treatment arms will be assessed, and adherence to the medications will be evaluated.

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: RCVS: The Rational Approach to Diagnosis and Treatment
Actual Study Start Date : July 1, 2017
Estimated Primary Completion Date : May 31, 2019
Estimated Study Completion Date : May 31, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Nimodipine
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Active Comparator: Nimodipine
Patients in group one will receive short-acting nimodipine every 4 hours.
Diagnostic Test: TCD- cerebral blood flow velocities
Participants will undergo daily TCD for monitoring of cerebral blood flow.
Behavioral: Headache pain score
Participants will be evaluated by nurses for headache frequency and severity every shift.
Other: Neurological examination
Patients will be examined routinely for evidence of neurological improvement/decline and/or evidence of a complication such as stroke or hemorrhage.
Diagnostic Test: Repeat Neuroimaging
All patients will also be seen at 90 days (+/- 30 days) and administered a headache diary, repeat neuroimaging, and neurological examination.
Drug: Nimodipine
Participants will be administered nimodipine every 4 hours.
Active Comparator: Verapamil ER
Patients in group two will receive long-acting verapamil every 12 hours.
Diagnostic Test: TCD- cerebral blood flow velocities
Participants will undergo daily TCD for monitoring of cerebral blood flow.
Behavioral: Headache pain score
Participants will be evaluated by nurses for headache frequency and severity every shift.
Other: Neurological examination
Patients will be examined routinely for evidence of neurological improvement/decline and/or evidence of a complication such as stroke or hemorrhage.
Diagnostic Test: Repeat Neuroimaging
All patients will also be seen at 90 days (+/- 30 days) and administered a headache diary, repeat neuroimaging, and neurological examination.
Drug: Verapamil ER
Participants will be administered long acting verapamil every 12 hours.


Outcome Measures

Primary Outcome Measures :
  1. Peak TCD velocities [ Time Frame: daily from admission to discharge (approx 5-7 days) ]
    Peak mean Cerebral Blood Flow velocity (CBFV) in anterior circulation vessels (MCA/Anterior Cerebral Artery (ACA)/Posterior Cerebral Artery (PCA)/internal carotid)

  2. Duration of elevated TCD velocities [ Time Frame: daily from admission to discharge (approx 5-7 days) ]
    Duration of elevated velocity (number of days from presentation to normalization/reduction)

  3. Normalization of TCD velocities [ Time Frame: daily from admission to discharge (approx 5-7 days) ]
    Normalization/reduction of velocity (yes/no)


Secondary Outcome Measures :
  1. Peak pain score [ Time Frame: every 8 hours while hospitalized (approx 5-7 days) and at 90 day follow-up ]
    Peak pain score- Likert scale evaluating headache: 0-10 points

  2. Days to pain resolution [ Time Frame: every 8 hours while hospitalized (approx 5-7 days) and at 90 day follow-up ]
    Number of days to resolution

  3. New or recurrent stroke/hemorrhage [ Time Frame: daily through hospitalization (approx 5-7 days) ]
    evaluated by neurological examinations and confirmed by imaging

  4. Modified Rankin Scale [ Time Frame: on hospital discharge and at 90 day follow-up ]
    functional outcome scale based on mobility and ability to perform activities of daily living- scale 0-6 points (0-2 considered good outcome)

  5. Repeat neuroimaging [ Time Frame: at 90 day follow-up ]
    repeat neuroimaging to confirm reversibility of vasculopathy

  6. Medication compliance [ Time Frame: daily throughout hospitalization (approx 5-7 days) and at 90 day follow-up ]
    ability to tolerate and adhere to medication


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Patients 18 years of age or greater meeting the following inclusion criteria adapted from Singhal and colleagues 2 will be included:

1. presentation consistent with RCVS :

  • acute thunderclap/severe headache and

    **supporting clinical features should prompt increased clinical suspicion (eg., potential medication trigger, recent pregnancy, migraine history)**

  • evidence of beading/elevated velocities on imaging (Transcranial Doppler (TCD), angiogram, Computer Tomography Angiogram (CTA), MRA) and
  • reversibility (by 90 days)-will not be required for inclusion but will be retrospectively adjudicated

Participants will be excluded from the study if they are:

  • unable to consent AND no family present to consent, or
  • have presence of aneurysmal, traumatic, or mesencephalic Subarachnoid Hemorrhage (SAH), or
  • have presence of other supported diagnosis (eg., vasculitis- inflammatory lumbar puncture) or
  • are currently pregnant or
  • the use of nimodipine or verapamil is contraindicated for any reason (eg., allergy, breast feeding) or
  • have limited TCD sonographic window

    • stroke or ICH/SAH on presentation will not be a contraindication to inclusion in the trial **
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03150524


Contacts
Contact: Elisabeth B Marsh, MD 4105508703 ebmarsh@jhmi.edu
Contact: Rafael H Llinas, MD 4105501042 rllinas@jhmi.edu

Locations
United States, Maryland
Johns Hopkins Bayview Medical Center Recruiting
Baltimore, Maryland, United States, 21210
Contact: Elisabeth B Marsh, MD    410-550-8703    ebmarsh@jhmi.edu   
Contact: Rafael H Llinas, MD    410-550-1042    rllinas@jhmi.edu   
Johns Hopkins Hospital Recruiting
Baltimore, Maryland, United States, 21287
Contact: Elisabeth B Marsh, MD    410-550-8703    ebmarsh@jhmi.edu   
Contact: Rafael H Llinas, MD    410-550-1042    rllinas@jhmi.edu   
Sponsors and Collaborators
Johns Hopkins University
Investigators
Principal Investigator: Elisabeth B Marsh, MD Johns Hopkins University
Principal Investigator: Rafael H Llinas, MD Johns Hopkins University
More Information

Additional Information:
Publications:
Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT03150524     History of Changes
Other Study ID Numbers: IRB00130191
First Posted: May 12, 2017    Key Record Dates
Last Update Posted: August 23, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Johns Hopkins University:
stroke
RCVS

Additional relevant MeSH terms:
Verapamil
Nimodipine
Anti-Arrhythmia Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Antihypertensive Agents