The Effect of Histamine H1 Receptor Antagonist, Clemastin, on PACAP38 Induced Headache in Migraine Patients

Study Overview
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Brief Summary
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The purpose of this study is to determine the effects of antihistamine (Clemastin) on migraines triggered by pituitary adenylate cyclase activating peptide-38 (PACAP38) as well as on biochemical markers for mast cell degranulation in migraine patients. Also, to investigate the occurrence of migraine in migraine patients after infusion of PACAP38 in lower dosages than previously investigated. As this has never been done before it is unknown how a lower dose of PACAP38 will affect 1) the incidence of migraine attacks, 2) the accompanying symptoms, 3) head pain characteristics, and 4) debut and duration of migraine attacks. Our three hypotheses are: Pre-treatment with Clemastin reduces PACAP38 sensitivity and inhibits development of migraine in migraine patients. Clemastin inhibits the increase in plasma concentration of TNF-alpha, histamine and tryptase after PACAP38-infusion. PACAP38 in lower dosages (4, 6 and 8 pmol/kg/min) induces migraine in migraine patients.

Detailed Description
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The purpose of this study is to determine the effects of antihistamine (Clemastin) on migraines triggered by pituitary adenylate cyclase activating peptide-38 (PACAP38) as well as on biochemical markers for mast cell degranulation in migraine patients. Also, to investigate the occurrence of migraine in migraine patients after infusion of PACAP38 in lower dosages than previously investigated. As this has never been done before it is unknown how a lower dose of PACAP38 will affect 1) the incidence of migraine attacks, 2) the accompanying symptoms, 3) head pain characteristics, and 4) debut and duration of migraine attacks.

Official Title
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The Effect of Histamine H1 Receptor Antagonist, Clemastin, on PACAP38 Induced Headache in Migraine Patients

Conditions
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Migraine Without Aura

Intervention / Treatment
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* Drug: PACAP38


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: migraine patients fulfilling IHS criteria for migraine without aura, ages 18-50, 50-100 kg, fertile women must be using safe prevention Exclusion Criteria: other types of primary headache than migraine headache on trial day or later than 48 hours before trial day migraine up to three days before trial day any type of cardiovascular disease clinical signs or patient history of any type of illness that the medical doctor in charge of trials deems relevant for participation

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 50 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

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo to PACAP38<br>Pre-treatment with placebo. PACAP38 8pmol/kg/min | Drug: PACAP38<br>* Giving doses of 4, 6 or 8 pg/kg/min on three separate trial days.<br>* Other names: Pituitary Adenylate Cyclase Activating Peptide 38;|
| Experimental: Clemastin 1 mg/ml to PACAP38 8pmol/kg/min<br>Pre-treatment with Clemastin 1 mg/ml PACAP38 8 pmol/kg/min | Drug: PACAP38<br>* Giving doses of 4, 6 or 8 pg/kg/min on three separate trial days.<br>* Other names: Pituitary Adenylate Cyclase Activating Peptide 38;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of migraine in migraine patients |  | Up to 12 months |