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

NCT04580238 | Withdrawn Phase 1 DMC

• 1 other identifier: Pro00104820
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Keywords

Botulinum Toxins, Type A; CVA; Stroke; Headache; Migraine

Outcome Measures

Primary Outcomes (3)

• Change in Number of Migraine Days

  Change in number of migraine days per month

  after completion of treatment cycles (2 years)

• Change in Number of Moderate to Severe Migraine Days.

  Change in Number of Moderate to Severe Migraine Days per month

  after completion of treatment cycles (2 years)

• Responder Rates

  proportion of patients who experience: a ≥50% reduction in headache days, a ≥50% reduction in moderate/severe headache days, a ≥50% reduction in total cumulative hours of headache on headache days and a ≥5- point improvement in HIT-6 scores.

  after completion of treatment cycles (2 years)

Secondary Outcomes (4)

• Headache Intensity

  after completion of treatment cycles (2 years)

• Cumulative hours per 28 days of moderate/severe pain:

  after treatment of completion cycles (2 years)

• Conversion to episodic migraine.

  after treatment of completion cycles (2 years)

• Scale for depression

  after treatment of completion cycles (2 years)

Other Outcomes (2)

• Headache Impact Test-6 (HIT-6)

  after treatment of completion cycles (2 years)

• Post Stroke Fatigue (Fatigue Severity Scale)

  after treatment of completion cycles (2 years)

Study Arms (2)

Treatment Arm

EXPERIMENTAL

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

Drug: Botox 200 UNT Injection

Control

ACTIVE COMPARATOR

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.

Combination Product: Non Botox based Standard of Care Treatments for Headache/Migraine

Interventions

Botox 200 UNT Injection 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

Also known as: onabotulinum toxin a

Treatment Arm

Non Botox based Standard of Care Treatments for Headache/Migraine COMBINATION_PRODUCT

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

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• Contraindications to Botox, neuromuscular illness or documented hyper- sensitivity will preclude randomization of patients.
• 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).
• CGRP inhibitors will be contraindicated during the period of study.

Sponsors & Collaborators

• University of Alberta: lead

Study Sites (1)

Division of Neurology, Grey Nuns Community Hospital

Edmonton, Alberta, T8B1C9, Canada

Location

Related Publications (8)

• 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.

  PMID: 25164919 RESULT

• 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.

  PMID: 29765218 RESULT

• 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.

  PMID: 30152015 RESULT

• 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.

  PMID: 30232673 RESULT

• 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.

  PMID: 27910097 RESULT

• 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.

  PMID: 25500317 RESULT

• 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.

  PMID: 26381856 RESULT

• 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.

  PMID: 30617735 RESULT

Related Links

• Helsinki Declaration

MeSH Terms

Conditions

Stroke; Migraine Disorders; Vertebral Artery Dissection; Hemorrhagic Stroke; Headache

Interventions

onabotulinum toxin A

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Headache Disorders, Primary; Headache Disorders; Cerebrovascular Trauma; Trauma, Nervous System; Dissection, Blood Vessel; Aneurysm; Wounds and Injuries; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Muzaffar M Siddiqui, MD

  University of Alberta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 2, 2020
• First Posted: October 8, 2020
• Study Start: December 1, 2023
• Primary Completion: January 1, 2025
• Study Completion: June 1, 2025
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)