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

NCT ID: NCT01924052

Last Updated: 2022-08-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-30
• Study Completion Date: 2013-08-31

Brief Summary

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).

Detailed 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.

Conditions

Migraine Without Aura

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

Migraine patients with high genetic load

CGRP intravenous infusion 1.5 microgram/min for 20 min

Group Type: ACTIVE_COMPARATOR

CGRP

Intervention Type: DRUG

Calcitonin-gene-related-peptide (CGRP)

Migraine patients with low genetic load

CGRP intravenous infusion 1.5 microgram/min for 20 min

Group Type: ACTIVE_COMPARATOR

CGRP

Intervention Type: DRUG

Calcitonin-gene-related-peptide (CGRP)

Interventions

CGRP

Calcitonin-gene-related-peptide (CGRP)

Intervention Type: DRUG

Other Intervention Names

calcitonin-gene-related peptide

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Danish Headache Center

OTHER

Sponsor Role: lead

Responsible Party

Song Guo

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Song Guo, MD

Role: PRINCIPAL_INVESTIGATOR

Danish Headache Center & Department of Neurology

Other Identifiers

H-2-2011-141

Identifier Type: -

Identifier Source: org_study_id