The Effect of PACAP27 on the Extra- and Intracerebral Arteries Assessed by Magnetic Resonance Angiography (MRA) on Healthy Volunteers

Study Overview
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Brief Summary
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Studying Pituitary adenylate cyclase-activating peptide 27 (PACAP27) effects on extra- and intracerebral arteries assessed by MRA on healthy volunteers.

Detailed Description
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PACAP neuropeptide, which belongs to the vasoactive intestinal polypeptide (VIP)/glucagon/secretin family. PACAP exists in two forms: Studying Pituitary adenylate cyclase-activating peptide 38 (PACAP38), which consists of 38 amino acids and PACAP27 which contains 27 amino acids at its N-terminus. PACAP38 is implicated in migraine pathophysiology however PACAP27 is not studied well. Therefore, the investigators will study PACAP27's effect on extra- and intracerebral arteries assessed by MRA on healthy volunteers.

Official Title
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The Effect of PACAP27 on the Extra- and Intracerebral Arteries Assessed by MRA on Healthy Volunteers

Conditions
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Headache, Migraine

Intervention / Treatment
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* Other: PACAP27
* Other: Placebo


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: Parallel Assignment
Interventional Model Description: 18 healthy volunteers will receive PACAP27 or placebo. All Data will also be analyses blinded.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PACAP27<br>12 healthy volunteers will receive PACAP27 (10 picomole/kg/min) over 20 min | Other: PACAP27<br>* PACAP27 is vasodilator of cerebral vessels<br>|
| Placebo Comparator: Placebo<br>6 healthy volunteers will receive placebo (Saline) over 20 min | Other: Placebo<br>* Saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dilation of extra- and intracerebral arteries | 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 five predefined time points (0, 20, 110, 200 and 290 min) | 0-290 min | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Headache | Headache intensity (Visual analog scale 0-10), characteristics, location and migraine associated symptoms will be recorded in questionnaire at hospital (6 hours) and post hospital (18 hours). In hospital phase, headache questionnaire will be filled every 30 min and post hospital every hour. | 0 to 24 hours |