PACAP38 Induced Headache, Migraine and Flushing in Patients With Migraine

Study Overview
=================
Brief Summary
-----------------
The aim is to investigate the incidence of headache, migraine attacks and flushing after pituitary adenylate cyclase-activating peptide-38 (PACAP38) with and without treatment with sumatriptan in patients with migraine

Detailed Description
-----------------
Pituitary adenylate cyclase-activating peptide-38 (PACAP38) plays a role in migraine pathophysiology. Infusions of PACAP38 can trigger migraine-like attacks in some migraine patients and will induce flushing in all patients. We are investigating whether treatment with sumatriptan has an effect on the PACAP38-induced flushing and on whether headache and migraine is induced. The purpose of this study is to investigate PACAP38-induced headache and migraine in patients with migraine who have been treated with either sumatriptan or placebo using purpose-developed standardized interview. The study will be conducted with a double-blind, placebo-controlled crossover study design.

Official Title
-----------------
Investigation of PACAP38 Induced Headache, Migraine and Flushing in Patients With Migraine

Conditions
-----------------
Migraine Without Aura

Intervention / Treatment
-----------------
* Drug: Imigran
* Other: Isotonic Saline
* Other: Pituitary adenylate cyclase-activating peptide-38


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: diagnosis of migraine, according to IHS criteria weight between 50 - 100 kilograms women in fertile age must not be pregnant and must use adequate contraception Exclusion Criteria: migraine more than 5 days per month in average over the past year any primary headache other than migraine, apart from tension-type headache which must be less than 5 days per month headache < 48 hours before experimental day migraine < 72 hours before each experimental day daily / frequent use of any medication apart from contraceptive medication use of any drug less than 5 times the half-life of the drug at the time of the experiment women who are pregnant or breast-feeding at the time of the experiment anamnestic or clinical signs of hypertension (systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg) or hypotension (systolic blood pressure < 90 mmHg and/or diastolic blood pressure < 50 mmHg) anamnestic or clinical signs of mental illness, or abuse of alcohol / drugs patients with glaucoma or prostate hyperplasia anamnestic or clinical symptoms of any sort that the investigating doctor deemed unfit for participating in the study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PACAP38 + Imigran<br>Pituitary adenylate cyclase-activating peptide-38 infusion (10 picomol/kg/min) for 20 mins AND Imigran infusion (0.4 mg/min) for 10 mins | Drug: Imigran<br>* All patients will undergo this intervention on one of two study days<br>* Other names: Sumatriptan;Other: Pituitary adenylate cyclase-activating peptide-38<br>* All patients will undergo this intervention on both study days<br>* Other names: PACAP38;|
| Placebo Comparator: PACAP38 + Isotonic Saline<br>Pituitary adenylate cyclase-activating peptide-38 infusion (10 picomol/kg/min) for 20 mins AND Isotonic saline for 10 mins (placebo) | Other: Isotonic Saline<br>* All patients will undergo this intervention on one of two study days<br>Other: Pituitary adenylate cyclase-activating peptide-38<br>* All patients will undergo this intervention on both study days<br>* Other names: PACAP38;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of migraine | Incidence of migraine after PACAP38-infusion will be estimated through a standardized interview based on the international headache classification for migraine | From 0 to 12 hours after infusion | 
| Effect of Sumatriptan | Severity of PACAP38-induced headache and migraine after pretreatment with sumatriptan in migraine patients measured by numerical rating scale for pain from 0 (no pain) to 10 (worst pain imaginable) | From 0 to 12 hours after infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of flushing | Facial skin blood flow (flushing) will be measured by laser doppler flowmetry to evaluate the severity of PACAP38-induced flushing with and without sumatriptan-treatment | From 0 to 4 hours after infusion | 
| Facial temperature | PACAP38-induced temperature changes with and without sumatriptan-treatment measured by infrared thermography | From 0 to 4 hours after infusion | 
| Superficial temporal artery diameter | Superficial temporal artery diameter after PACAP38 with and without sumatriptan-treatment measured by ultrasound | From 0 to 4 hours after infusion | 
| Severity of headache | Severity of PACAP38-induced headache will be rated on a numerical rating scale for pain from 0 (no pain) to 10 (worst pain imaginable) | From 0 to 12 hours after infusion |