Reversible Cerebral Vasoconstriction SyndromePhase 4NCT03150524
RCVS: The Rational Approach to Diagnosis and Treatment
A Phase 4 study testing TCD- cerebral blood flow velocities, Headache pain score and Neurological examination in people with Reversible Cerebral Vasoconstriction Syndrome, run by Johns Hopkins University at 2 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Reversible Cerebral Vasoconstriction Syndrome
- What is being tested?
- TCD- cerebral blood flow velocities, Headache pain score and Neurological examination
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Jul 2017to 31 May 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Patients 18 years of age or greater meeting the following inclusion criteria adapted from Singhal and colleagues 2 will be included:
- 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 **
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, 21210
Johns Hopkins Hospital
Baltimore, Maryland, 21287
About this study
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).
Read the 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.
- Being tested
- TCD- cerebral blood flow velocities, Headache pain score, Neurological examination, Repeat Neuroimaging, Nimodipine
- Keywords
- stroke, RCVS
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TCD- cerebral blood flow velocitiesDiagnostic test
Participants will undergo daily TCD for monitoring of cerebral blood flow.
Headache pain scoreBehavioural
Participants will be evaluated by nurses for headache frequency and severity every shift.
Neurological examinationOther
Patients will be examined routinely for evidence of neurological improvement/decline and/or evidence of a complication such as stroke or hemorrhage.
Repeat NeuroimagingDiagnostic test
All patients will also be seen at 90 days (+/- 30 days) and administered a headache diary, repeat neuroimaging, and neurological examination.
NimodipineDrug
Participants will be administered nimodipine every 4 hours.
Verapamil ERDrug
Participants will be administered long acting verapamil every 12 hours.
| Study group | Role | What they receive |
|---|---|---|
| Nimodipine | Active comparator | Patients in group one will receive short-acting nimodipine every 4 hours. Receives: Diagnostic Test: TCD- cerebral blood flow velocities; Behavioral: Headache pain score; Other: Neurological examination; Diagnostic Test: Repeat Neuroimaging; Drug: Nimodipine |
| Verapamil ER | Active comparator | Patients in group two will receive long-acting verapamil every 12 hours. Receives: Diagnostic Test: TCD- cerebral blood flow velocities; Behavioral: Headache pain score; Other: Neurological examination; Diagnostic Test: Repeat Neuroimaging; Drug: Verapamil ER |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak TCD velocities
Peak mean Cerebral Blood Flow velocity (CBFV) in anterior circulation vessels (MCA/Anterior Cerebral Artery (ACA)/Posterior Cerebral Artery (PCA)/internal carotid)
Measured: daily from admission to discharge (approx 5-7 days)
Duration of elevated TCD velocities
Duration of elevated velocity (number of days from presentation to normalization/reduction)
Measured: daily from admission to discharge (approx 5-7 days)
Normalization of TCD velocities
Normalization/reduction of velocity (yes/no)
Measured: daily from admission to discharge (approx 5-7 days)
Secondary outcomes (6)
Peak pain score
Peak pain score- Likert scale evaluating headache: 0-10 points
Measured: every 8 hours while hospitalized (approx 5-7 days) and at 90 day follow-up
Days to pain resolution
Number of days to resolution
Measured: every 8 hours while hospitalized (approx 5-7 days) and at 90 day follow-up
New or recurrent stroke/hemorrhage
evaluated by neurological examinations and confirmed by imaging
Measured: daily through hospitalization (approx 5-7 days)
Modified Rankin Scale
functional outcome scale based on mobility and ability to perform activities of daily living- scale 0-6 points (0-2 considered good outcome)
Measured: on hospital discharge and at 90 day follow-up
Repeat neuroimaging
repeat neuroimaging to confirm reversibility of vasculopathy
Measured: at 90 day follow-up
Medication compliance
ability to tolerate and adhere to medication
Measured: daily throughout hospitalization (approx 5-7 days) and at 90 day follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2017
- Study start1 Jul 2017
- Primary completion31 May 2019
- Study completion31 May 2019
Why it stopped: Failure to recruit patients meeting inclusion criteria.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Reversible Cerebral Vasoconstriction SyndromeStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Elisabeth B Marsh, MD, Principal investigator, Johns Hopkins UniversityRafael H Llinas, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03150524
- Sponsor's protocol ID
- IRB00130191
- Status last verified
- Sep 2019
- First submitted
- 8 May 2017
- Last updated
- 18 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Singhal AB, Hajj-Ali RA, Topcuoglu MA, Fok J, Bena J, Yang D, Calabrese LH. Reversible cerebral vasoconstriction syndromes: analysis of 139 cases. Arch Neurol. 2011 Aug;68(8):1005-12. doi: 10.1001/archneurol.2011.68. Epub 2011 Apr 11.
PubMed 21482916Marsh EB, Ziai WC, Llinas RH. The Need for a Rational Approach to Vasoconstrictive Syndromes: Transcranial Doppler and Calcium Channel Blockade in Reversible Cerebral Vasoconstriction Syndrome. Case Rep Neurol. 2016 Jul 29;8(2):161-171. doi: 10.1159/000447626. eCollection 2016 May-Aug.
PubMed 27721780
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RCVS: The Rational Approach to Diagnosis and Treatment
- ClinicalTrials.gov ID
- NCT03150524
- Acronym / sponsor ID
- IRB00130191
- Keywords
- stroke, RCVS
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Failure to recruit patients meeting inclusion criteria.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Study start
- 1 Jul 2017 (actual)
- Primary completion
- 31 May 2019 (actual)
- Study completion
- 31 May 2019 (actual)
- First posted
- 12 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nimodipine | Active comparator | Diagnostic Test: TCD- cerebral blood flow velocities, Behavioral: Headache pain score, Other: Neurological examination, Diagnostic Test: Repeat Neuroimaging, Drug: NimodipinePatients in group one will receive short-acting nimodipine every 4 hours. |
| Verapamil ER | Active comparator | Diagnostic Test: TCD- cerebral blood flow velocities, Behavioral: Headache pain score, Other: Neurological examination, Diagnostic Test: Repeat Neuroimaging, Drug: Verapamil ERPatients in group two will receive long-acting verapamil every 12 hours. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TCD- cerebral blood flow velocitiesParticipants will undergo daily TCD for monitoring of cerebral blood flow. | Diagnostic test | Nimodipine, Verapamil ER |
| Headache pain scoreParticipants will be evaluated by nurses for headache frequency and severity every shift. | Behavioural | Nimodipine, Verapamil ER |
| Neurological examinationPatients will be examined routinely for evidence of neurological improvement/decline and/or evidence of a complication such as stroke or hemorrhage. | Other | Nimodipine, Verapamil ER |
| Repeat NeuroimagingAll patients will also be seen at 90 days (+/- 30 days) and administered a headache diary, repeat neuroimaging, and neurological examination. | Diagnostic test | Nimodipine, Verapamil ER |
| NimodipineParticipants will be administered nimodipine every 4 hours. | Drug | Nimodipine |
| Verapamil ERParticipants will be administered long acting verapamil every 12 hours. | Drug | Verapamil ER |
Primary outcome
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)
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)
Normalization of TCD velocities
Time frame: daily from admission to discharge (approx 5-7 days)
Normalization/reduction of velocity (yes/no)
6 secondary outcomes
Peak pain score
Time frame: 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
New or recurrent stroke/hemorrhage
Time frame: daily through hospitalization (approx 5-7 days)
Modified Rankin Scale
Time frame: on hospital discharge and at 90 day follow-up
Repeat neuroimaging
Time frame: at 90 day follow-up
Medication compliance
Time frame: daily throughout hospitalization (approx 5-7 days) and at 90 day follow-up
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2019.
- Background: PubMed 21482916Singhal AB, Hajj-Ali RA, Topcuoglu MA, Fok J, Bena J, Yang D, Calabrese LH. Reversible cerebral vasoconstriction syndromes: analysis of 139 cases. Arch Neurol. 2011 Aug;68(8):1005-12. doi: 10.1001/archneurol.2011.68. Epub 2011 Apr 11.
- Background: PubMed 27721780Marsh EB, Ziai WC, Llinas RH. The Need for a Rational Approach to Vasoconstrictive Syndromes: Transcranial Doppler and Calcium Channel Blockade in Reversible Cerebral Vasoconstriction Syndrome. Case Rep Neurol. 2016 Jul 29;8(2):161-171. doi: 10.1159/000447626. eCollection 2016 May-Aug.
- Johns Hopkins School of Medicine Stroke Division WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Reversible Cerebral Vasoconstriction Syndrome
Active, not recruitingObservational study
Florida Cerebrovascular Disease Biorepository and Genomics Center
Cerebrovascular Disease, Ischemic Stroke
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elisabeth B Marsh, MD principal investigator
Johns Hopkins University
Rafael H Llinas, MD principal investigator
Johns Hopkins University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing TCD- cerebral blood flow velocities, Headache pain score and Neurological examination in people with Reversible Cerebral Vasoconstriction Syndrome, run by Johns Hopkins University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 18 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peak TCD velocities (time frame: daily from admission to discharge (approx 5-7 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03150524, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2019.