Onabotulinum Toxin A (Botox) for the Treatment of Persistent Post-Stroke and Vascular Headache

NCT ID: NCT04580238

Last Updated: 2024-09-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1

Study Classification

INTERVENTIONAL

Study Start Date

2023-12-31

Study Completion Date

2025-06-30

Brief Summary

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Post stroke headache occurs in approximately 10-23% of all stroke patients. Its onset is shortly after experiencing a stroke, or stroke like event, and persists for at least three months. These headaches have features which resemble migraine or occur in people who have a previous history of migraine that was once infrequent. Botox is a treatment that is currently approved for the treatment of chronic migraine, that is migraine headaches occurring for at least 15 days a month for at least 3 months. Given the clinical similarity in character and frequency of post stroke headache and migraine, and the fact that stroke affects structures like the blood vessels in the brain that are also affected in migraine, this study is to investigate the possible role that Botox would have in the treatment of Post-Stroke Headache.

Detailed Description

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The proposed study will be a randomized, open-label, comparator controlled study investigating the safety and efficacy of Botox in Persistent Post "Stroke" (encompassing ischemic stroke, hemorrhagic stroke, CVST, Cervical Vessel Dissection and RCVS) headache patients relative to Placebo with or without concomitant standard pharmacologic and Non-pharmacologic treatments.

The study population will be a stratified random sample of stroke patients fulfilling the inclusion criteria and consenting to study. The study groups will consist of 40 patients randomly allocated to receiving Botox according to the treatment regime specified below and 40 patients randomly allocated to Non-Botox standard treatments, to a total study population of 80 patients.

A Screening Questionnaire will be developed allowing for the identification of persistent/chronic post stroke headache and the classification into novel vs previous stable migraine sub-groups. Such dichotomization will not affect randomization process up and until one sub-group total had been met. If one arm is met prematurely, the Data and Safety Monitoring Committee will inform study investigators and only patients of the remaining sub-population will be randomized post- screening (stratified random sampling).

To facilitate Data collection and monitoring. Patients will be seen in face to face encounters every 12 weeks with interim phone interviews every 4 weeks. A cross platform mobile based application (Migraine Buddy, Healint Analytics)15 will be utilized with patient subjects to allow for documentation of migraine attacks including severity and the facility of real-time documentation of temporal profile, migraine triggers, and medications as well as facility for remote monitoring by study investigators. Subjects will be taught how to use application to export data to study investigators in order to allow timely a communication of potential adverse and serious adverse events.

Additionally, the investigators will be undergoing a retrospective analysis of headache patients treated at the Grey Nuns Community Hospital Stroke Clinic in order to add to the literature regarding the clinical characteristics and putative treatment effects in this unique patient population.

Treatment Protocol:

Botox 200 IU vials for 40 patients for the duration of study (4 treatment cycles); Treatment will be based on the PREEMPT study full treatment and follow the pain protocol to a total of 195 IU in standard injection sites.

Conditions

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Stroke (CVA) or TIA Headache, Migraine Botulinum Toxins, Type A Cerebral Venous Sinus Thrombosis Carotid Dissection Artery Vertebral Dissection Artery Hemorrhagic Stroke Reversible Cerebral Vasoconstriction Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

The proposed study will be a randomized, open-label, comparator controlled study investigating the safety and efficacy of Botox in Persistent Post "Stroke" (encompassing ischemic stroke, hemorrhagic stroke, CVST, Cervical Vessel Dissection and RCVS) headache patients relative to Placebo with or without concomitant standard pharmacologic and Non-pharmacologic treatments.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment Arm

The treatment group will consist of 40 patients randomly allocated to receiving Botox according to the treatment regime.

Group Type EXPERIMENTAL

Botox 200 UNT Injection

Intervention Type DRUG

Treatment Protocol:

Botox 200 IU vials for 40 patients for the duration of study (4 treatment cycles); Treatment will be based on the PREEMPT study full treatment (standard of care) and follow the pain protocol to a total of 195 IU in standard injection sites

Control

The control group will consist of 40 patients randomly allocated to Non-Botox, standard of care treatments, to a total study population of 80 patients.

Group Type ACTIVE_COMPARATOR

Non Botox based Standard of Care Treatments for Headache/Migraine

Intervention Type COMBINATION_PRODUCT

Control Group will receive normal standard of care Non-Botox based interventions.

Interventions

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Botox 200 UNT Injection

Treatment Protocol:

Botox 200 IU vials for 40 patients for the duration of study (4 treatment cycles); Treatment will be based on the PREEMPT study full treatment (standard of care) and follow the pain protocol to a total of 195 IU in standard injection sites

Intervention Type DRUG

Non Botox based Standard of Care Treatments for Headache/Migraine

Control Group will receive normal standard of care Non-Botox based interventions.

Intervention Type COMBINATION_PRODUCT

Other Intervention Names

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onabotulinum toxin a

Eligibility Criteria

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Inclusion Criteria

1. Adult patients (\>18 y) fulfilling ICHD-3 criteria\* of persistent post stroke/hemorrhagic stroke headache; persistent headache post dissection\* and post RCVS persistent headache will be enrolled at 3 months or greater of persistence of symptoms.

For the purposes of this study, as suggested elsewhere in the literature, the initial onset of headache will be considered for study if occurring within 72 hours prior to and 7 days post sentinel vascular event ("Stroke"). The 72 hours prior criteria allowing for inclusion of patients of intracerebral hemorrhage who are known to have anticipatory headache as well as alternate ischemic syndromes in which new onset headache may anticipate stroke symptoms such as dissection and reversible cerebro-vasoconstriction syndrome.
2. The syndrome of post CVST headache patients will only be enrolled after symptoms have persisted for a minimum of 6 months and after relevant imaging demonstrates a resolution of potentially structural contribution from the sentinel event (i.e. recanalization or chronic thrombo- sis with a normal opening pressure on lumbar puncture).

* Note the patients of post dissection persistent headaches may be enrolled despite the absence of an identified ischemic lesion, i.e. in the setting of TIA or new onset headache without embolic symptoms but with a history of the (stabilized) vascular injury associated with the syndrome.
* Note the co-existence of medication overuse headache will not be a contraindication to randomization.

Exclusion Criteria

1. Tension type Post Stroke Persisting Headache, Post stroke pain syndrome such as the Thalamic syndrome of Dejerine-Roussy, or any headache semiology that does not fulfill diagnostic criteria for chronic migraine, will be excluded.
2. Contraindications to Botox, neuromuscular illness or documented hyper- sensitivity will preclude randomization of patients.
3. Concurrent active systemic illness, such as sepsis, chronic infective processes, neoplastic syndromes, or autoimmune syndromes. (Headache secondary to medical illness, even if occurring post-stroke).
4. Subjects must be screened for coexistent (including psychiatric) conditions to exclude illnesses that may influence the conduct or results of the trial. Subjects with coexisting conditions, such as depression, may be included if they are defined a priori, stable on current treatment regimens (with no anticipated changes in management that may interfere with study results), and recorded throughout the study. One of the secondary outcome measures in the study investigates the potential impact on concurrent symptoms of depression. However, the stability of symptoms treatment and concomitant medications should be assessed prior to inclusion in the study. If factors are identified which might interfere with patient compliance, follow up or confound results, such patients should be excluded. Other common reasons for exclusion include severe depression and overuse of alcohol or illicit drugs, as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition.
5. CGRP inhibitors will be contraindicated during the period of study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Alberta

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Muzaffar M Siddiqui, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alberta

Locations

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Division of Neurology, Grey Nuns Community Hospital

Edmonton, Alberta, Canada

Site Status

Countries

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Canada

References

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Hansen AP, Marcussen NS, Klit H, Kasch H, Jensen TS, Finnerup NB. Development of persistent headache following stroke: a 3-year follow-up. Cephalalgia. 2015 Apr;35(5):399-409. doi: 10.1177/0333102414545894. Epub 2014 Aug 27.

Reference Type RESULT
PMID: 25164919 (View on PubMed)

Inanc Y, Orhan FO, Inanc Y. The effects of Maras powder use on patients with migraine. Neuropsychiatr Dis Treat. 2018 May 7;14:1143-1148. doi: 10.2147/NDT.S164818. eCollection 2018.

Reference Type RESULT
PMID: 29765218 (View on PubMed)

Lai J, Harrison RA, Plecash A, Field TS. A Narrative Review of Persistent Post-Stroke Headache - A New Entry in the International Classification of Headache Disorders, 3rd Edition. Headache. 2018 Oct;58(9):1442-1453. doi: 10.1111/head.13382. Epub 2018 Aug 27.

Reference Type RESULT
PMID: 30152015 (View on PubMed)

Gallerini S, Marsili L, Bartalucci M, Marotti C, Chiti A, Marconi R. Headache secondary to cervical artery dissections: practice pointers. Neurol Sci. 2019 Mar;40(3):613-615. doi: 10.1007/s10072-018-3576-y. Epub 2018 Sep 19.

Reference Type RESULT
PMID: 30232673 (View on PubMed)

Aurora SK, Brin MF. Chronic Migraine: An Update on Physiology, Imaging, and the Mechanism of Action of Two Available Pharmacologic Therapies. Headache. 2017 Jan;57(1):109-125. doi: 10.1111/head.12999. Epub 2016 Dec 2.

Reference Type RESULT
PMID: 27910097 (View on PubMed)

Silberstein SD, Dodick DW, Aurora SK, Diener HC, DeGryse RE, Lipton RB, Turkel CC. Per cent of patients with chronic migraine who responded per onabotulinumtoxinA treatment cycle: PREEMPT. J Neurol Neurosurg Psychiatry. 2015 Sep;86(9):996-1001. doi: 10.1136/jnnp-2013-307149. Epub 2014 Dec 12.

Reference Type RESULT
PMID: 25500317 (View on PubMed)

Maasumi K, Thompson NR, Kriegler JS, Tepper SJ. Effect of OnabotulinumtoxinA Injection on Depression in Chronic Migraine. Headache. 2015 Oct;55(9):1218-24. doi: 10.1111/head.12657. Epub 2015 Sep 18.

Reference Type RESULT
PMID: 26381856 (View on PubMed)

Klinedinst NJ, Schuh R, Kittner SJ, Regenold WT, Kehs G, Hoch C, Hackney A, Fiskum G. Post-stroke fatigue as an indicator of underlying bioenergetics alterations. J Bioenerg Biomembr. 2019 Apr;51(2):165-174. doi: 10.1007/s10863-018-9782-8. Epub 2019 Jan 7.

Reference Type RESULT
PMID: 30617735 (View on PubMed)

Related Links

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Other Identifiers

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Pro00104820

Identifier Type: -

Identifier Source: org_study_id

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