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

Not Applicable

Completed

• Conditions: Migraine Without Aura
• Interventions: Drug: PACAP

• Registration Number: NCT02158221
• Lead Sponsor: Danish Headache Center

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 PACAP 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 this genetic variant in humans are yet unknown.

PACAP is a neuropeptide which plays a crucial role in the pathophysiology of migraine and is present in migraine relevant structures. PACAP can induce migraine attacks in MO patients via an adenosine monophosphate (cAMP) dependent pathway. Also, a recent study has showed that intracellular accumulation of cAMP is crucial for the induction of migraine attacks.

The phenotype of the migraine inducing effects of PACAP might therefore be linked to some of the 12 genetic susceptibility loci that have been identified.

Study Timeline

• Study Start: 2014-06
• Study First Submitted: 2014-06-05
• Study First Submitted QC: 2014-06-05
• Study First Posted: 2014-06-06
• Primary Completion: 2014-11
• Study Completion: 2014-12
• Status Verified: 2015-02
• Last Update Submitted: 2015-02-09
• Last Update Posted: 2015-02-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Migraine patients with high genetic load	PACAP	PACAP intravenous infusion 1.5 microgram/min for 20 min
Migraine patients with low genetic load	PACAP	PACAP intravenous infusion 1.5 microgram/min for 20 min

Primary Outcome Measures

Name	Time	Method
Incidence of migraine attacks induced by PACAP in patients with high and low genetic load.	Change from baseline in headache intensity at 12 hours after the start of infusion of PACAP	The difference in incidence of migraine-like attacks after PACAP between patients with and without high genetic load and patients with low genetic load using verbal rating scale (VRS).

Secondary Outcome Measures

Name	Time	Method
Incidence of headache induced by PACAP in patients with high and low genetic load.	Change from baseline in headache intensity at 12 hours after the start of infusion of PACAP	The difference in area under the curve (AUC) for headache intensity scores (0-12 hours) after infusion of PACAP

Trial Locations

Locations (1)

Danish Headache Center & Department of Neurology; 🇩🇰 Copenhagen, Glostrup, Denmark