Novel Insight Into Migraine Pathophysiolgy and Galcanezumab Mechanisms of Action

Beth Israel Deaconess Medical Center1 个研究点分布在 1 个国家目标入组 64 人开始时间: 2020年7月29日最近更新: 2026年3月24日

适应症

干预措施

试验速览

阶段: 4 期
状态: 已完成
发起方: Beth Israel Deaconess Medical Center
入组人数: 64
试验地点: 1
主要终点: Change in Gray Matter Thickness in the Left Medial Superior Frontal Gyrus

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The purpose of this study is to understand better the mechanisms of action of calcitonin gene related peptide (CGRP) targeted monoclonal antibodies in migraine prevention. Specifically, the protocol will allow the investigators to determine whether the main site of action of this novel and recently-approved class of migraine prophylactic drugs act inside or outside the brain and if so, where.

详细描述

A brief overview of the study: To test the working hypothesis of the study, the investigators propose to study 60 chronic migraine (CM)/high-frequency episodic migraine (HFEM) patients in 4 visits to the Beth Israel Deaconess Medical Center (BIDMC) Comprehensive Headache Center and 2 visits to the imaging center at McLean Hospital. The first 3 visits to BIDMC Comprehensive Headache Center and the first visit to McLean Hospital will take place before treatment, whereas the 4th visit to BIDMC Comprehensive Headache Center and the second visit to McLean Hospital will take place 3 months after initiation of treatment. In these visits, the investigators will collect medical and headache history, perform a physical examination, administer and review subjects' e-diary, and perform functional and structural fMRI brain imaging (see flow chart).

Overall study design: Experimental prospective study involving identification of neurological effects after treatment of CM and HFEM with galcanezumab - an anti-CGRP-monoclonal antibody (mAb).

Design methodologies: Open-label treatment study comparing the effects of galcanezumab on neurological functioning and brain structure in super-responders, responders and non-responders among CM and HFEM patients.

Primary goal: To determine whether galacanezumab - a drug that acts mainly outside the brain - reverses abnormal brain functioning in CM and HFEM patients. For this study, signs of abnormal brain functioning include triggering of migraine by deviation from homeostasis (prodromes, sleep deprivation, skipping meals) and abnormal sensitivity to sensory stimuli (light, noise, smell, auras).

Key details of study implementation: The study includes CM and HFEM patients. The intervention is galacanezumab (Emgality™). Galcanezumab is an anti-CGRP-mAb approved by the FDA for the prophylactic treatment of migraine. Because this is not an efficacy study, the primary endpoint will not include reduction in number of migraine/headache days per month. Rather, the primary endpoints of the study will include the following: incidence of prodromes, incidence of triggers, sensitivity to light, noise and smell during and in between attacks, and incidence of aura (as determined by filling the e-diary), gray mater thickness and connectivity strength between brain areas involved in migraine (as determined by fMRI). Each patient will be scheduled to visit the headache clinic at BIDMC 4 times and the McLean Hospital Pain Imaging Center twice (a total of 6 hospital visits). Visits 1 and 6 (at BIDMC) will take 1 hour. Visits 2 and 4 (at BIDMC) will take 30 min. Visits 3 and 5 (at McLean Hospital) will take 2 hours. In addition, each patient will have to fill a daily diary for 4 months (estimated to take 5 minutes per day), and will receive a 5 minute weekly phone call from a study coordinator.

研究设计

研究类型: Interventional
分配方式: Na
干预模型: Single Group
主要目的: Basic Science
盲法: None

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

•Between the ages of 18 and 65 years
•Been previously diagnosed with migraine (with or without aura), in accordance with the ICHD-3 (International Classification of Headache Disorders) criteria
•Experiences between 10 to 25 headaches days per month (during the last 3 months), with at least 8 of them being migraine days during which the migraines lasted more than 4 hours if untreated
•Onset of migraine at age 50 years or younger
•Agrees to refrain from initiating or changing the type, dosage, or frequency of any prophylactic medications for indications other than migraine that may interfere with the study objectives (e.g., antidepressants, anticonvulsants, beta-adrenergic blockers, etc.)
•Able to provide written informed consent

排除标准

•Currently on a regimen of 1 or more migraine preventative therapy
•Other significant pain problem (e.g., cancer pain, fibromyalgia, other head or facial pain disorder) that may confound the study assessments
•Known or suspected severe cardiac disease (e.g., symptomatic coronary artery disease, prior myocardial infarction, congestive heart failure)
•Known or suspected cerebrovascular disease (e.g., prior stroke or transient ischemic attack, symptomatic carotid artery disease, prior carotid endarterectomy or other vascular neck surgery)
•Abnormal baseline electrocardiogram (ECG) within the last year (e.g., second or third-degree heart block, prolonged QT interval, atrial fibrillation, atrial flutter, history of ventricular tachycardia or ventricular fibrillation, clinically significant premature ventricular contraction)
•Uncontrolled high blood pressure (systolic >160 mm Hg, diastolic >100 mm Hg) after 3 measurements within 24 hours
•Known history or suspicion of secondary headache
•Known history or suspicion of substance abuse or addiction (within the last 5 years)
•Currently using marijuana (including medical marijuana) or has used marijuana (including medical marijuana) or cannabidiol oil within the last 1 year
•Currently takes simple analgesics or NSAIDs >15 days per month or triptans, ergots, or combined analgesics >10 days per month for headaches or other body pain
•Currently takes prescription opioids for headaches or body pain
•Undergone nerve block (occipital or other) in the head or neck within the last 3 months
•Received botulinum toxin or anti-CGRP-mAb injections within the last 6 months
•Pregnant or thinking of becoming pregnant during the study period, or of childbearing years and unwilling to use an accepted form of birth control
•Participating in any other therapeutic clinical investigation or has participated in a clinical trial in the preceding 30 days
•Belongs to a vulnerable population or has any condition such that his or her ability to provide informed consent, comply with the follow-up requirements, or provide self-assessments is compromised.
•A relative of or an employee of the Investigator or the clinical study site
•Psychiatric or cognitive disorder and/or behavioral problems that, in the opinion of the clinician, may interfere with the study
•History of claustrophobia

研究组 & 干预措施

Treatment

Other

Effects of galacenezumab (emgality) treatment (injectable 240 mg initial dose followed by 120 mg treatments 1 and 2 month later) on brain functioning.

干预措施: Emgality 120 MG in 1 ML Prefilled Syringe (Drug)