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

Not Applicable

• Conditions: Migraine
• Interventions: Other: Placebo; Drug: Calcitonin Gene-Related Peptide

• Registration Number: NCT03481400
• Lead Sponsor: Danish Headache Center

Brief Summary

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

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.

Study Timeline

• Study Start: 2016-07
• Status Verified: 2018-03
• Study First Submitted: 2018-03-13
• Study First Submitted QC: 2018-03-27
• Last Update Submitted: 2018-03-27
• Study First Posted: 2018-03-29
• Last Update Posted: 2018-03-29
• Primary Completion: 2019-09
• Study Completion: 2019-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Infusion with placebo (isotonic saline)
Calcitonin gene-related peptide	Calcitonin Gene-Related Peptide	Calcitonin gene-related peptide infusion (1.5 micrograms/min for 20 mins)

Primary Outcome Measures

Name	Time	Method
Area under the curve of headache intensity	From 0 to 90 minutes after infusion and from 90 minutes to 12 hours after infusion	Area under the curve of headache intensity from 0-90 min and 90 min-12 hours post infusion
Incidence of migraine	From 0 to 12 hours after CGRP infusion	Incidence of migraine after CGRP infusion

Secondary Outcome Measures

Name	Time	Method
Heart rate	From 0 to 90 minutes after infusion	Heart rate (beats per minute)
Blood pressure	From 0 to 90 minutes after infusion	Blood pressure (millimeter of mercury)

Trial Locations

Locations (1)

Danish Headache Center, Rigshospitalet Glostrup; 🇩🇰 Copenhagen, Glostrup, Denmark