Exploratory Study of the Natural History, Clinical Outcomes, and Neuronal Endplate Changes in Subjects Reporting Short Duration vs. Long Duration of Benefit for OnabotulinumtoxinA in Treatment of Chronic Migraine
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Subject Global Impression of Change
研究概览
简要总结
To obtain a patient specific understanding of response to treatment with onabotulinumtoxinA by collecting and correlating pre and post treatment subject specific history, clinical outcomes, and histological changes.
详细描述
Recognizing a commitment to evidence-based science as the pathway to optimize clinical outcomes for patients with chronic migraine (CM) we believe this investigator initiated study (IIS) will:
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Help clinicians recognize the importance of scheduling patients with CM at intervals not exceeding 12 weeks.
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Provide biopsy evidence supporting sensory mechanisms involved in the mechanism of action (MOA) of onabotulinumtoxinA (BTX). This does not exclude potential valuable contributions of denervation of motor neurons, but may support a more balanced and understandable mechanism for BTX in treating CM.
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Provide clinicians important educational information for patients to better manage expectations of using BTX in managing CM and answering critical questions such as:
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How long does it take for BTX to begin providing a clinical benefit?
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What is the expected duration of this benefit?
- Failure to understand unmet expectations either real or otherwise results in defining BTX treatment as a failure by patients and/or clinicians.
- Provide validation for patients' reports of shorter duration of action of BTX so patients will not be misinterpreted as non-responders to BTX prematurely.
- Ascertain if subjects initially reporting short duration of BTX response continue to experience this similar pattern of effect with repeated injection cycles.
- Provide the first detailed longitudinal assessment of BTX response.
- Correlate the onset and duration of benefit for subjects receiving BTX.
- Observe factors predictive of duration of BTX response.
This study proposes to accomplish these goals through an exploratory comparison of the clinical efficacy and natural history of BTX measured at weekly time intervals. Subjects reporting short (<10 weeks) duration of benefit and subjects reporting long (>10 weeks) duration of clinical benefit will provide the primary comparison. Histological examinations (in a subset of subjects) of neuronal changes associated with regeneration of terminal neuronal endplates will be used to support these clinical observations. This study will follow subjects through 3 injection cycles or 36 weeks. Biopsies will be performed on consenting subjects prior to their first and second injection cycles.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •male or female 18 years or older.
- •able to read, understand, and sign the informed consent.
- •a negative urine pregnancy test at visit 1, if female, and of childbearing potential. Note: If female of childbearing potential, subject must agree to maintain true abstinence or use one of the listed methods of birth control for the duration of the study: hormonal contraceptive, intrauterine device (IUD), condoms, diaphragm, and/or have a male partner who has undergone a successful vasectomy. The use of barrier contraceptive (condom or diaphragm) should always be supplemented with the use of a spermicide.
- •Note: To be considered not of childbearing potential, subject must be 6 weeks post-surgical bilateral oophorectomy, hysterectomy, bilateral tubal ligation, postmenopausal for at least one year.
- •at least a one year history of migraine
- •history of chronic migraine (with or without aura) according to the criteria of the International Classification of Headache Disorders (ICHD)-3 for at least 3 months prior to enrollment (Appendix I)
- •able to differentiate migraine headache from any other headache they may experience (e.g., cluster headache)
- •onset of migraine before age 50
- •willing to provide responses to questionnaires and complete the online diary.
- •if taking migraine preventive(s), be on a stable dose of the preventive medication for at least 30 days prior to screening
- •concomitant medication dosages approved by the investigator
- •email and internet access for completion of online diary
排除标准
- •previously used onabotulinumtoxinA as a migraine preventative or has used onabotulinumtoxinA for any other reason during the prior year
- •female who is pregnant, planning to become pregnant during the study period, breast feeding, or is of childbearing potential and not practicing a reliable form of birth control
- •headache disorders outside ICHD-3 defined chronic migraine that cannot be easily distinguished from CM (Appendix I)
- •evidence of underlying pathology contributing to their headaches
- •any medical condition that may increase their risk with exposure to BTX including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or any other significant disease that might interfere with neuromuscular function
- •profound atrophy or weakness of muscles in the target areas of injection
- •skin conditions or infections at any of the injection sites
- •allergy or sensitivities to any component of the test medication
- •in the opinion of the investigator, has an active major psychiatric disorder including substance abuse and/or substance dependence within the last 12 months as determined by the investigator.
- •Medication Overuse Headache as defined by ICHD-3 criteria for opioid or butalbital containing products (Appendix II)
- •planning or requiring surgery during the study
- •a history of poor compliance with medical treatment
- •currently participating in an investigational drug study or has participated in an investigational drug study within the previous 30 days of the screening visit
研究组 & 干预措施
onabotulinumtoxinA
At visit 2, subjects will receive their first treatment at Day 29 (+/-3 days). All subjects will receive 155 U Botulinum Toxin Type A Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven (7) specific head/neck muscle areas. Injections will be repeated at day 113 (+/- 3 days) and at day 197 (+/- 3 days).
干预措施: onabotulinumtoxinA (Drug)
结局指标
主要结局
Subject Global Impression of Change
时间窗: Weeks 12, 24, and 36 Post Randomization
Changes in the Subject's Global Impression of Change (SGIC) measured at weeks 12, 24, and 36 for Groups A, B, and C. Subject global impression of change was measured on a 7 point scale with 0 being Very Much Worse and 7 Very Much Improved.
Duration of onabotulinumtoxinA Over 3 Injection Cycles in Groups A, B, and C
时间窗: From day 29 (first day of injection cycle 1) to day 281 (84th day of injection cycle 3) plus or minus 12 days
Compare the duration of onabotulinumtoxinA response through the 3 injection cycles of the study for Groups A, B, and C as measured by headache days during each period (Baseline (28 days), Treatment Period 1(84 days), Treatment Period 2(84 days), and Treatment Period 3(84 days). Duration of response is defined as a 30% reduction in the number of headache days compared to baseline.
次要结局
- Social Readjustment Rating Scale (SRRS)(Baseline, Week 12, Week 24, and Week 36 Post Randomization)
- Headache Days(From day 29 (first day of injection cycle 1) to day 281 (84th day of injection cycle 3) plus or minus 12 days)
- Physician Global Impression of Change (PGIC)(Week 12, Week 24, and Week 36 Post Randomization)
- Beck Depression Inventory II (BDI-II)(Baseline, Week 12, Week 24, and Week 36 Post Randomization)
- Acute Medication Usage(From day 1 (first day of baseline) to day 281 (84th day of injection cycle 3) plus or minus 12 days)
- Duration of onabotulinumtoxinA Over 3 Injection Cycles(Weeks 9, 10, 11, 12, 21, 22, 23, 24, 33, 34, 35, 36 Post Randomization)
- Migraine Disability Assessment Scale (MIDAS)(Baseline, Week 12, Week 24, and Week 36 Post Randomization)
- State-Trait Anxiety Inventory (STAI)(Baseline, Week 12, Week 24, and Week 36 Post Randomization)
- Sleep Quality Question(Baseline, Week 12, Week 24, and Week 36 Post Randomization)
- Consistency of Response to onbotulinumtoxinA Over Three Injection Cycles(Weeks 12, 24, and 36 Post Randomization)