CGRP Induced Migraine Attacks in Patients With High and Low Genetic Load

Danish Headache Center

Status: Completed

Conditions: Migraine Without Aura

Treatments: Drug: CGRP

Study type: Interventional

Funder types: Other

Identifiers

NCT01924052

H-2-2011-141

Details and patient eligibility

About

The investigators hypothesized that migraine without patients with many genetic loci associated with migraine (high genetic load) would be more sensitive and get provoked more migraine attacks by calcitonin gene-related peptide (CGRP) compared to patients with few genetic loci associated with migraine (low genetic load).

Full description

Migraine is a very prevalent neurological disorder with a strong genetic factor. The common forms of migraine have a multifactorial and polygenic pattern of inheritance and genetics research is crucial for a deeper understanding of migraine mechanisms. Recently, 12 genetic loci have been identified to be associated with migraine with (MA) and without aura (MA) in four large genome-wide association studies (GWAS). The functional consequences of these genetic loci in humans are yet unknown.

Calcitonin gene-related peptide (CGRP) is a neuropeptide which plays a crucial role in the pathophysiology of migraine and is present in migraine relevant structures. CGRP can induce migraine attacks in MO patients via an adenosine monophosphate (cAMP) dependent pathway and CGRP antagonism is efficient in the treatment of migraine attacks. Also, a recent study has showed that intracellular accumulation of cAMP is crucial for the induction of migraine attacks. However, CGRP does not cause migraine attacks in familial hemiplegic migraine (FHM), an autosomal dominant subtype of MA.

The phenotype of the migraine inducing effects of CGRP might therefore be linked to some of the 12 genetic susceptibility loci that have been identified. One of the genetic loci (rs13208321) is located in a gene (FHL5) that is associated with the regulation of cAMP-responsive elements.

Enrollment: 40 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Migraine without aura patients genotyped for the 12 newly idetified gene variants associated with migraine.

Exclusion criteria

• Other primary headache
• A history of cerebrovascular disease and other CNS- disease
• A history suggesting ischaemic heart disease
• Serious somatic and mental disease
• Hypo- or hypertension
• Abuse of alcohol or medicine (opioid analgesics).
• Pregnant or breastfeeding women.

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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40 participants in 2 patient groups

Migraine patients with high genetic load

Active Comparator group

Description:

CGRP intravenous infusion 1.5 microgram/min for 20 min

Treatment:

Drug: CGRP

Migraine patients with low genetic load

Active Comparator group

Description:

CGRP intravenous infusion 1.5 microgram/min for 20 min

Treatment:

Drug: CGRP