Predict the Response to Acute Treatment of Migraine With Rimegepant 75 mg

Study Overview
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Brief Summary
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Tools to predict which patients could better respond to abortive CGRP target therapy are still lacking. We propose to investigate if biochemical (salivary CGRP) and neurophysiological (evoked potentials) biomarkers can recognize patients with the best chances of responding to Rimegepant 75 mg as an acute treatment of migraine.

Detailed Description
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Background: The understanding of the central role of CGRP in migraine pathophysiology led to the development of new target therapies against this molecule pathway, including Rimegepant. Despite the central role of the CGRP pathway in migraine, it was recently discovered that some migraine attacks are non CGRP-dependent. Tools to predict which patients could better respond to abortive CGRP target therapy are still lacking. Objective: We propose to investigate if biochemical (salivary CGRP) and neurophysiological (evoked potentials) biomarkers can recognize patients with the best chances of responding to Rimegepant 75 mg as an acute treatment of migraine. Design of the study and methods: This will be a prospective observational study. The study will be subdivided into four phases: screening visit (T0), salivary collection, observational phase, follow-up visit (T1). At the screening visit (T0) patients with episodic migraine (20 patients), which will be prescribed Rimegepant 75 mg as abortive treatment, will be asked to participate in the study. During the salivary collection phase, patients will be instructed to collect daily saliva samples for a minimum of 7 days and a maximum of 14 days to include a minimum of 1 migraine attack. During the observational phase (1-month duration) patients will take Rimegepant 75 mg for abortive treatment of migraine attacks and, they will be instructed to take extra saliva samples (headache onset, after 2h and 8h) at each migraine attack. Neurophysiological procedures (somatosensory evoked potentials and nociceptive blink reflex) will be recorded at baseline (T0) and after 1 month (follow-up visit, T1) of administration of Rimegepant 75 mg as an abortive migraine treatment. We chose somatosensory evoked potentials (SSEPs) to assess the integrity of the non-pain-related somatosensory lemniscal system and to study habituation phenomena, and nociceptive blink reflex (nBR) to investigate the activity of the caudal trigeminal nucleus. CGRP salivary levels will be quantified with ELISA kit. Specific aim: We aim to predict Rimegepant (used as abortive therapy) response from baseline CGRP salivary levels and neurophysiological parameters (habituation and sensitization from somatosensory evoked potentials and nociceptive blink reflex). Mixing and comparing these two approaches could help to find a combination of biomarkers able to predict the treatment success. We hypothesize that patients with marked habituation deficit, less sensitization, and more elevated CGRP salivary levels during the attack will be the patients who will respond the most to Rimegepant 75 mg as abortive migraine therapy.

Official Title
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How to Predict Response to Acute Treatment of Migraine With Rimegepant 75 mg: a Biochemical and Neurophysiological Study.

Conditions
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Migraine Disorders

Intervention / Treatment
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* Drug: Rimegepant 75 milligrams


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of Episodic migraine Prescription of Rimegepant 75 mg as abortive treatment for migraine headache occurring on < 15 days/four weeks; No other primary/secondary headache disorder; No contraindication for Rimegepant 75 mg; No previous exposure to any anti-CGRP drugs; No prophylactic migraine treatment ongoing or in the past 3 months before participation in the study Exclusion Criteria: headache occurring >15 days/four weeks Contraindication for Rimegepant 75 mg Previous exposure to anti-CGRP drugs; Prophylactic migraine treatment ongoing or in the past 3 months before participation in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Episodic migraine patients<br>20 patients with episodic migraine (<15 attacks/month) will be recruited from a specialized headache Clinic (headache clinic of the Sapienza University of Rome, Latina). | Drug: Rimegepant 75 milligrams<br>* At the screening visit patients with episodic migraine, which will be prescribed Rimegepant 75 mg as abortive treatment, will be asked to participate in the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Salivary CGRP levels during attacks | In order to identify a biomarker that predicts the Rimegepant's response | from enrollment to one month after the start of therapy | 
| Relationship between Rimegepant's response and salivary CGRP levels | Differences between responders and not responders to Rimegepant and salivary CGRP levels (pg/ml). | from enrollment to one month after the start of therapy | 
| Relationship between Rimegepant's response and habituation at baseline | Differences between responders and not responders to Rimegepant and habituation (microvolt) at baseline. | from enrollment to one month after the start of therapy | 
| Relationship between Rimegepant's response and sensitization at baseline | Differences between responders and not responders to Rimegepant and sensitization (microvolt) at baseline. | from enrollment to one month after the start of therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of Rimegepant 75 mg on habituation after 1 month of therapy | Comparison between habituation (microvolt) at baseline and habituation (microvolt) after one month of abortive therapy with Rimegepant 75 mg | one month after the start of therapy | 
| Changes from Baseline in the sensitization after 1 month of therapy | Comparison between sensitization (microvolt) at baseline and sensitization (microvolt) after one month of abortive therapy with Rimegepant 75 mg | one month after the start of therapy | 
| Changes from Baseline in the pain threshold after 1 month of therapy | Comparison between pain threshold (mA) at baseline and pain threshold (mA) after one month of abortive therapy with Rimegepant 75 mg | one month after the start of therapy | 
| Changes from Baseline in the sensory detection threshold after 1 month of therapy | Comparison between sensory detection threshold (mA) at baseline and sensory detection threshold (mA) after one month of abortive therapy with Rimegepant 75 mg | one month after the start of therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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migraine biomarkers, neurophysiology, CGRP, salivary CGRP, habituation, sensitization, Rimegepant