RCVS: The Rational Approach to Diagnosis and Treatment

September 16, 2019 updated by: Johns Hopkins University
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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Hospital
      • Baltimore, Maryland, United States, 21210
        • Johns Hopkins Bayview Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 **

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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)
daily from admission to discharge (approx 5-7 days)
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)
daily from admission to discharge (approx 5-7 days)
Normalization of TCD velocities
Time Frame: daily from admission to discharge (approx 5-7 days)
Normalization/reduction of velocity (yes/no)
daily from admission to discharge (approx 5-7 days)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
every 8 hours while hospitalized (approx 5-7 days) and at 90 day follow-up
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
every 8 hours while hospitalized (approx 5-7 days) and at 90 day follow-up
New or recurrent stroke/hemorrhage
Time Frame: daily through hospitalization (approx 5-7 days)
evaluated by neurological examinations and confirmed by imaging
daily through hospitalization (approx 5-7 days)
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)
on hospital discharge and at 90 day follow-up
Repeat neuroimaging
Time Frame: at 90 day follow-up
repeat neuroimaging to confirm reversibility of vasculopathy
at 90 day follow-up
Medication compliance
Time Frame: daily throughout hospitalization (approx 5-7 days) and at 90 day follow-up
ability to tolerate and adhere to medication
daily throughout hospitalization (approx 5-7 days) and at 90 day follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Johns Hopkins University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Elisabeth B Marsh, MD, Johns Hopkins University
  • Principal Investigator: Rafael H Llinas, MD, Johns Hopkins University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 31, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 31, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 8, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 9, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 12, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 18, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 16, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB00130191

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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