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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Migraine Without Aura

Intervention / Treatment
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* Drug: PACAP


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Migraine patients with high genetic load<br>PACAP intravenous infusion 1.5 microgram/min for 20 min | Drug: PACAP<br>* Pituitary adenylate cyclase-activating polypeptide (PACAP)<br>* Other names: Pituitary adenylate cyclase-activating polypeptide;|
| Active Comparator: Migraine patients with low genetic load<br>PACAP intravenous infusion 1.5 microgram/min for 20 min | Drug: PACAP<br>* Pituitary adenylate cyclase-activating polypeptide (PACAP)<br>* Other names: Pituitary adenylate cyclase-activating polypeptide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of migraine attacks induced by PACAP in patients with high and low genetic load. | 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). | Change from baseline in headache intensity at 12 hours after the start of infusion of PACAP | 

Secondary Outcome Measures

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