The Role of Inflammation and Vasodilatation in PACAP38-induced Headache Using MRI on Healthy Subjects

Study Overview
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Brief Summary
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Studying Pituitary adenylate cyclase-activating peptide 38 (PACAP38) induced headache effects on extra- and intracerebral arteries and pre-posttreated by sumatriptan and ketorolac assessed by magnetic resonance imaging (MRI) on healthy volunteers.

Detailed Description
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The purpose of this research project is to investigate the importance of blood vessel (vasodilatation), vessel wall inflammation and blood flow in arteries of headaches triggered by PACAP38 and for headache treated with sumatriptan (migraine medicine) and ketorolac (NSAID). In addition, we will investigate headache-related changes in the brain's network connectivity.

Official Title
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The Role of Inflammation and Vasodilatation in PACAP38-induced Headache Using MRI on Healthy Subjects

Conditions
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Headache

Intervention / Treatment
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* Other: Sumatriptan
* Other: Ketorolac


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers Aged 18-50 50-100 kg Exclusion Criteria: Tension type headache more than 5 dag /month Other primary headaches Daily medication except contraceptives Drug taken within 4 times the half-life for the specific drug except contraceptives Pregnant or lactating women Exposure to radiation within the last year Headache within the last 24 hours before start of trial Hypertension Hypotension Respiratory or cardiac disease Primary relatives with current or previous migraine

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Each participant will receive PACAP28 intravenous infusion over 20 min in both experiment days but treated in randomized order with sumatriptan or ketorolac.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Sumatriptan<br>Sumatriptan 4 mg/mL I.V will be administrated over 10 min | Other: Sumatriptan<br>* Receive intravenous infusion of sumatriptan<br>|
| Active Comparator: Ketorolac<br>Ketorolac 30 mg/mL I.V will be administrated over 10 min | Other: Ketorolac<br>* Receive intravenous infusion of ketorolac<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intra-extra cerebral arteries vasodilatation | PACAP38 vasodilatation reverse by sumatriptan but not ketorolac. A single-slab 3D time-of-flight (3D TOF) MRA of extra- and intracranial arteries will be acquired as described in previous studies (Amin et al., 2013, 2014). MRA data will be analyzed by LKEB-MRA vessel wall analysis software program. We will measure the circumference of vessels in millimeter in 4 predefined time points (0, 20, 60 and 110 min) | 120 minutes | 
| Headache score | Visual analog Scale | 6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood pressure | vital parameters recorded at hospital phase | 2 hours | 
| Headache characteristics | Standard headache questionnaire will be used to record headache localization, nausea, photo and phonophobia. | 24 hours | 
| Heart rate | vital parameters recorded at hospital phase | 2 hours |