CGRP-induced Migraine Attacks in Patients Who Have Tried Anti-CGRP Monoclonal Antibody Treatment

Study Overview
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Brief Summary
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The investigators aim to investigate the incidence of migraine attacks after calcitonin gene-related peptide (CGRP) infusion in patients who have tried anti-CGRP monoclonal antibody treatment for the prevention of migraine.

Detailed Description
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Calcitonin gene-related peptide (CGRP) plays a role in migraine pathophysiology. Infusions of CGRP can trigger migraine-like attacks in migraine patients and antibodies against CGRP or the CGRP receptor significantly reduces the number of migraine days per month when administered regularly. Some patients however, do not experience migraine attack after CGRP infusion, and some do not experience migraine reduction with antibodies. The underlying mechanisms of these effects are largely unknown. The purpose of this study is to examine CGRP-induced migraine in patients who have evaluated the efficacy of anti-CGRP monoclonal antibody treatment for migraine using a purpose-developed standardized interview. The investigators will use a double-blind, placebo-controlled crossover study design to examine migraine susceptibility to CGRP in these patients.

Official Title
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Provoked Migraine Attacks With Calcitonin Gene-related Peptide (CGRP) in Patients Who Have Tried Preventive Treatment With Anti-CGRP Monoclonal Antibodies.

Conditions
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Migraine

Intervention / Treatment
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* Drug: Calcitonin Gene-Related Peptide
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of migraine according to the international classification of headache disorders version 3-beta Subject has tried anti-CGRP antibodies for migraine Women of childbearing potential are on safe contraception Exclusion Criteria: Women of childbearing potential who do not use contraception. Includes non-hysterectomized women who have not been menopausal for at least two years. Safe contraception includes condoms, intrauterine devices, p-pills, surgical sterilization or gestagen injections. Daily drug intake apart from contraceptives and preventive medication for migraine. Ingestion of any drug 4 half-lifes before study start apart from contraceptives. Pregnant or breast-feeding women Migraine on the study day or less than 48 hours before CGRP infusion. A history of cardiovascular and/or cerebrovascular disease Systolic blood pressure >150 mmHg and/or diastolic blood pressure > 100 mmHg on study day. Systolic blood pressure <90 mmHg and/or diastolic blood pressure < 50 mmHg on study day. A history of mental illness A history of any illness or condition that is deemed relevant for participation by the investigator.

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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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Placebo-controlled, crossover design.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Calcitonin gene-related peptide<br>Calcitonin gene-related peptide infusion (1.5 micrograms/min for 20 mins) | Drug: Calcitonin Gene-Related Peptide<br>* Calcitonin gene-related peptide intravenous infusion (1.5 micrograms/min for 20 mins)<br>* Other names: CGRP;|
| Experimental: Placebo<br>Infusion with placebo (isotonic saline) | Other: Placebo<br>* Isotonic saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of migraine | Incidence of migraine after CGRP infusion | From 0 to 12 hours after CGRP infusion | 
| Area under the curve of headache intensity | Area under the curve of headache intensity from 0-90 min and 90 min-12 hours post infusion | From 0 to 90 minutes after infusion and from 90 minutes to 12 hours after infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart rate | Heart rate (beats per minute) | From 0 to 90 minutes after infusion | 
| Blood pressure | Blood pressure (millimeter of mercury) | From 0 to 90 minutes after infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Calcitonin gene-related peptide