Calcitonin Gene-related Peptide (CGRP) Levels in the Pathogenesis of Chronic Migraine
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Change in Number of Headache Days Per Month From Baseline (BL) to Months 1 Through 7.
研究概览
简要总结
Twenty patients will be enrolled in a 2-site, 7-month, double-blind study conducted to evaluate a reduction in headache days and attacks and calcitonin gene-related peptide (CGRP) levels in saliva following treatment with OnabotulinumtoxinA versus saline.
Eligible patients will be randomized and receive injections of OnabotulinumtoxinA or Saline at Visit 1. Following 3 months plus a 1 month wash out, patients will receive cross-over injections at Visit 5.
Patients will return for monthly visits and exit the study at Visit 8.
Patients will collect saliva at monthly intervals and document in a daily headache diary throughout the study .
详细描述
This double-blind study will evaluate reduction in number of headache days following treatment with OnabotulinumtoxinA versus Saline. Additionally, CGRP levels in saliva will be correlated with a reduction in headache attacks.
At Visit 1, eligible subjects will be randomized 1:1 to receive injections of OnabotulinumtoxinA or Saline in an identical manner. Subjects will collect 3 saliva samples during each month of the 7 month study: 1 collection at Baseline headache level, 1 collection at onset of headache that is one degree worse than Baseline level that will be treated with acute therapy, and 1 collection at 2 hours following treatment. Subjects will document headache and headache symptoms in a daily diary and return to the clinic with diary and saliva samples at monthly visits.
Following 4 months (including a 1 month washout after Visit 4), subjects will return at Visit 5 and receive cross-over injections. Subjects randomized to OnabotulinumtoxinA at Visit 1 will receive injections of Saline. Subjects randomized to saline at Visit 1 will receive injections of OnabotulinumtoxinA. Subjects will document headache and headache symptoms in a daily diary and return to the clinic with diary and saliva samples at monthly visits.
At Visit 8, 3 months following re-injection at Visit 5, subjects will exit the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •must be outpatient, male or female, of any race, between 18 and 65 years of age.
- •if female of childbearing potential must have negative pregnancy test result at Screening Visit and practice reliable method of contraception.
- •A female is considered of childbearing potential unless she is post menopausal for at least 12 months prior to administration of study drug, without a uterus and/or both ovaries or has been surgically sterilized for at least 6 months prior to study drug administration.
- •Reliable methods of contraception are: Complete abstinence from intercourse from 2 weeks prior to administration of the investigational product, throughout the study, and for a time interval (5 days) after completion or premature discontinuation from the study; or, History of bilateral tubal ligation; or, Sterilization of male partner; or, Implants of levonorgestrel; or, Injectable progestogen; or, Oral contraceptive (combination therapy with ethinyl estradiol plus a progestin) with a placebo week every 1-3 months; or, Any intrauterine device (IUD) with published data showing that the highest expected failure rate is less than 1% per year (not all IUD's meet this criterion) in use at least 30 days prior to study drug administration; or, Spermicide plus a mechanical barrier (e.g., spermicide plus a male condom or a female diaphragm); or, Any other barrier methods (only is used in combination with any of the above acceptable methods) in use at least 14 days prior to study drug administration; or, Any other methods with published data showing that the highest expected failure rate for that methods is less than 1% per year.
- •must have history of chronic migraine (with or without aura) according to the criteria proposed by the Headache Classification Committee of the International Headache Society (IHS) for at least 3 months prior to enrollment.
- •must be able to understand the requirements of the study including maintaining a headache Diary, and signing informed consent.
- •must be in good general health as determined by investigator.
- •if taking migraine preventive, must be on a stable dose of preventive medication for at least 3 months prior to screening.
排除标准
- •if female, is pregnant, planning to become pregnant during the study period, is breast feeding, or is of childbearing potential and not practicing a reliable form of birth control.
- •has headache disorders outside IHS-defined chronic migraine definition.
- •has evidence of underlying pathology contributing to their headaches.
- •has any pathology of the salivary glands such as sialadenitis (e.g. Sjogren's syndrome, viral or bacterial sialadenitis) or condition or symptom that would alter the content of saliva.
- •has any medical condition that may increase their risk with exposure to OnabotulinumtoxinA including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or any other significant disease that might interfere with neuromuscular function.
- •has profound atrophy or weakness of muscles in the target areas of injection.
- •has skin conditions or infections at any of the injection sites.
- •has allergy or sensitivities to any component of the test medication.
- •who in the opinion of the investigator, has active major psychiatric or depressive disorders including alcohol/drug abuse.
- •meets International Headache Society criteria for Medication Overuse with opioid or butalbital containing products.
- •is planning or requiring surgery during the study.
- •has a history of poor compliance with medical treatment.
- •is 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
Minimum dose of 155 international units (U) OnabotulinumtoxinA Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven specific head/neck muscle areas.
干预措施: OnabotulinumtoxinA (Drug)
Saline
155 U Saline administered at 31 fixed-site, fixed-dose injections across seven specific head/neck muscle areas.
干预措施: Saline (Drug)
结局指标
主要结局
Change in Number of Headache Days Per Month From Baseline (BL) to Months 1 Through 7.
时间窗: Baseline (collected historically at screening) versus (vs.) Month (Mo) 1, Mo 2, Mo 3, Mo 4, Mo 5, Mo 6, and Mo 7
Baseline number of headache days per month collected historically at screening. Post-treatment number of headache days collected per month via diary.
Change in Number of Headache Days Per Month From Baseline to Month 1 (M1), Month 1 to Month 2 (M2), and Month 2 to Month 3 (M3).
时间窗: Baseline (collected historically at screening) vs. Mo 1, Mo 1 vs. Mo 2, Mo 2 vs. Mo 3, Mo 3 vs. Mo 4, Mo 4 vs. Mo 5, Mo 5 vs. Mo 6, and Mo 6 vs. Mo 7
Baseline number of headache days per month collected historically at screening. Post-treatment number of headache days collected per month via diary.
次要结局
- Inter-ictal (Baseline) Levels of Saliva Calcitonin Gene-related Peptide (CGRP)(Baseline levels collected for OnabotulinumtoxinA and Saline treatment during Months 1 through 7)
- Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline(For OnabotulinumtoxinA and Saline treatment months 1, 2 and 3)
- Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders(For OnabotulinumtoxinA and Saline treatment months 1, 2 and 3 at Baseline level (inter-ictal) and at onset of headache that is one degree worse than Baseline level and that will be treated with acute therapy)