Unraveling the Spectrum of Migraine Resistant to Treatments: Searching for Novel Biological PHEnotypes and theRApeutic Approaches (SPHERA Project)

What this Trial Is About

Researchers are investigating the role of the endocannabinoid system (eCBome) in patients with migraine disorders, including episodic and chronic migraine. The study focuses on patients undergoing preventive treatment with monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway. The goal is to identify biological differences between patients who respond to this therapy with a significant reduction in monthly migraine days and those who do not, helping to understand why some patients resist current treatments. Participants receive mAbs treatment either monthly or quarterly, with assessments conducted before starting treatment (baseline) and after three months. The study groups include responders, who achieve at least a 50% reduction in monthly migraine days, and non-responders, who do not reach this threshold. Various biochemical markers, such as gene expressions related to eCBome enzymes, neuropeptides, inflammatory cytokines, kynurenine metabolites, microRNAs, and microbiota profiles, are measured to create a detailed biological profile. Throughout the study, patients provide blood and stool samples under controlled conditions to evaluate these biochemical markers. Sampling occurs in the morning during the migraine-free phase to reduce variability. Researchers analyze changes in gene expression and plasma levels of several substances over the three-month treatment period. The primary outcomes focus on gene expression changes of FAAH and MAGL enzymes. Safety and response are monitored, with data used to explore novel biological signatures that may guide future migraine therapies. The total study duration for each participant is approximately three months.

Biochemical Profiling of Migraine Patients