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

Migraine Without Aura Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01924052
• Other study ID #: H-2-2011-141
• Status: Completed
• Phase: N/A
• Start date: June 2013
• Est. completion date: August 2013

Study information

• Verified date: July 2022
• Source: Danish Headache Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: August 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Migraine Disorders
• Migraine without Aura

Intervention

Drug:
• CGRP
Calcitonin-gene-related-peptide (CGRP)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Danish Headache Center

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CGRP induced migraine attacks in patients with high and low genetic load	The difference in incidence of migraine-like attacks between patients with high genetic load and patients with low genetic load using verbal rating scale (VRS).	Change from baseline in headache intensity at 12 hours after the start of infusion of CGRP
Secondary	CGRP induced migraine attacks in patients with high and low genetic load	The difference in area under the curve (AUC) for headache intensity scores (0-12 hours)	Change from baseline in headache intensity at 12 hours after the start of infusion of CGRP