Onabotulinum Toxin A (Botox) for the Treatment of Persistent Post-Stroke and Vascular Headache
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Change in Number of Migraine Days
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •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.
排除标准
- •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).
- •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.
- •CGRP inhibitors will be contraindicated during the period of study.
研究组 & 干预措施
Treatment Arm
The treatment group will consist of 40 patients randomly allocated to receiving Botox according to the treatment regime.
干预措施: Botox 200 UNT Injection (Drug)
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.
干预措施: Non Botox based Standard of Care Treatments for Headache/Migraine (Combination Product)
结局指标
主要结局
Change in Number of Migraine Days
时间窗: after completion of treatment cycles (2 years)
Change in number of migraine days per month
Change in Number of Moderate to Severe Migraine Days.
时间窗: after completion of treatment cycles (2 years)
Change in Number of Moderate to Severe Migraine Days per month
Responder Rates
时间窗: after completion of treatment cycles (2 years)
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.
次要结局
- Scale for depression(after treatment of completion cycles (2 years))
- 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))