Clinical trial NCT03481400: CGRP-induced Migraine Attacks in Patients Who Have Tried Anti-CGRP Monoclonal Antibody Treatment
Official title: Provoked Migraine Attacks With Calcitonin Gene-related Peptide (CGRP) in Patients Who Have Tried Preventive Treatment With Anti-CGRP Monoclonal Antibodies.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Migraine
Keywords: Calcitonin gene-related peptide
Lead sponsor: Danish Headache Center
Sponsor class: OTHER
First posted: 2018-03-29
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Placebo-controlled, crossover design.
Primary purpose: OTHER

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of migraine
timeFrame: From 0 to 12 hours after CGRP infusion
measure: Area under the curve of headache intensity
timeFrame: From 0 to 90 minutes after infusion and from 90 minutes to 12 hours after infusion
Secondary outcomes:
measure: Heart rate
timeFrame: From 0 to 90 minutes after infusion
measure: Blood pressure
timeFrame: From 0 to 90 minutes after infusion
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Danish Headache Center, Rigshospitalet Glostrup
state: Glostrup
Study officials:
affiliation: Danish Headache Center
name: Messoud Ashina, prof.
role: STUDY_DIRECTOR
References:
citation: Christensen CE, Younis S, Deen M, Khan S, Ghanizada H, Ashina M. Migraine induction with calcitonin gene-related peptide in patients from erenumab trials. J Headache Pain. 2018 Nov 8;19(1):105. doi: 10.1186/s10194-018-0927-2.