Novel Insight Into Migraine Pathophysiolgy and Galcanezumab Mechanisms of Action
brief summary
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.
detailed description
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.