A RandomizEd, Double-blind, Cross-over Study to Assess Erenumab effecT on BRAIN Networks Function and Structure in Comparison to Placebo in Episodic Migraine Patients
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- z-score maps difference between clinical response groups within the two treatment groups.
研究概览
简要总结
The purpose of this study is to investigate the effects of erenumab on central sensitization and brain networks connectivity of migraine patients
详细描述
This is a randomized, double blind, placebo-controlled trial with a 2-sequence, 2-period, 2-treatment crossover design. The study population will consist of adult male and female subjects with a documented history of episodic migraine (4 to 14 baseline migraine days), who have failed at least 2 previous migraine prophylactic treatment for lack of efficacy or tolerability. After a run-in phase of 4 weeks, patients will be randomized, according to a 1:1 ratio, to a 24 weeks of treatment, as follow:
- Sequence 1: A/B
- Sequence 2: B/A where: A=monthly subcutaneous erenumab 140 mg for 12 weeks; B=monthly subcutaneous masked placebo for 12 weeks
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Study treatments will be all identical in packaging, labeling, schedule of administration, appearance, taste and odor
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
- •Signed informed consent must be obtained prior to participation in the study History of migraine with or without aura for at least 12 months prior to screening
- •Migraine frequency: ≥ 4 and < 15 migraine days per month on average across the 3 months prior to screening and confirmed during the baseline phase based on diary calculation
- •Headache frequency: <15 headache days per month on average across the 3 months prior to screening and confirmed during the baseline phase based on diary calculation
- •Failure to 2 or more previous treatment categories locally indicated for migraine prophylaxis due to either lack of efficacy or poor tolerability
排除标准
- •History of cluster headache or hemiplegic migraine headache
- •History of chronic pain disorders and neuropathic pain
- •History of head trauma or seizure or major psychiatric disorders or suicidal ideation/behavior at any time before screening
- •Currently, receiving any other prophylactic treatment for migraine and/or prohibited medications, non-pharmacologic interventions or devices (any substance, non-pharmacologic intervention or device acting at central nervous system), or less than 60 days or 5 half-lives prior to the start of the baseline period, during the baseline period, or treatment period
- •Exposure to botulinum toxin in the head and/or neck region within 4 months prior to the start of the baseline period, during the baseline period, or treatment period.
- •Taken the following for any indication in any month during the 2 months prior to the start of the baseline period:
- •Ergotamines or triptans on ≥ 10 days per month, or
- •Simple analgesics (non-steroidal anti-inflammatory drugs [NSAIDs], acetaminophen) on ≥ 15 days per month, or
- •Opioid- or butalbital-containing analgesics on ≥4 days per month.
- •Previous exposure to erenumab or exposure to any other prophylactic CGRP-targeted therapy (prior to and during the study)
- •History or evidence of any other unstable or clinically significant medical condition that in the opinion of the investigator would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion
- •Subject has any clinically significant vital sign, laboratory, or electrocardiogram (ECG) abnormality during screening that, in the opinion of the investigator, could pose a risk to subject safety or interfere with the study evaluation
- •Evidence of drug or alcohol abuse or dependence within 12 months prior to screening, based on medical records or patient self-report
- •Pregnant or breastfeeding
- •All the clinical conditions for which undergoing an MRI scan is contraindicated
研究组 & 干预措施
erenumab
monthly subcutaneous erenumab 140 mg for 12 weeks
干预措施: erenumab (Drug)
placebo
monthly subcutaneous masked placebo for 12 weeks.
干预措施: placebo (Drug)
结局指标
主要结局
z-score maps difference between clinical response groups within the two treatment groups.
时间窗: baseline, month 3, month 6
clinical response assessed as reduction by 50% in monthly migraine days ,MMD, in the last month vs baseline. z score maps relative to resting state functional connectivity strength in the brain areas involved in pain processing
z-score maps change difference between-treatment-groups
时间窗: baseline, month 3, month 6
z score maps are measures of resting state functional connectivity strength in the brain areas involved in pain processing
次要结局
- Between-treatment-groups difference in change of resting state functional connectivity strength, from baseline to month 3 of treatment, measured as z-score maps. in the brain regions involved in migraine symptoms(baseline, month 3, month 6)
- Correlation (by treatment group and in all patients) between of the changes in the resting state functional connectivity strength of the areas involved in migraine symptoms and the reduction of the respective symptoms(month 3, month 6)
- Correlation (by treatment groups and in all patients) between the changes in the resting state functional connectivity strength, measured as z-score maps, and clinical outcomes(month 3, month 6)
- Baseline resting state functional connectivity strength will be evaluated by treatment group and in all patients as potential predictors of treatment clinical response defined by the achievement of at least 50% reduction of monthly migraine days(baseline, month 3, month 6)
- Changes in z-score maps from baseline to month 3 of erenumab treatment and from baseline to month 6 with 3 months with erenumab followed by 3 months of placebo(baseline, month 3, month 6)