PACAP-38 Infusion in Patients With Cluster Headache

Study Overview
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Brief Summary
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A randomized, double-blinded, two-way crossover study investigating the headache inducing capabilities of PACAP-38 in patients with cluster headache. Forty-five patients (15 episodic patients in cluster, 15, episodic patients in remission and 15 chronic cluster headache patients) are expected to participate. Each patients will on two separate study days in a randomized way receive an infusion of PACAP-38 and VIP over 20 minutes followed by an observation period of 70 minutes. Blood samples for investigation of VIP, PACAP38; CGRP, NSE, Histamine and Tryptase will be drawn at fixed time-points during experiment.

Official Title
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The Effect of PACAP-38 Infusion in Inducing Headache in Patients With Cluster Headache

Conditions
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Cluster Headache

Intervention / Treatment
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* Other: Evaluation of headache inducing capabilities of PACAP38


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Episodic or chronic cluster headache according to international classification of headache disorders Age 18-65 years Weight 50-100 kg If women of childbearing potential, then must use safe contraceptives Exclusion Criteria: Episodic tension-type headache > 15 days per month Other primary headache disorders, except tension-type headache < 5 days per month Episodic cluster headache patients outside cluster must be completely headache free a minimum of 8 hours prior to experiment Episodic cluster headache patients in cluster and chronic cluster headache patients must be completely headache free a minimum of 4 hours prior to experiment Current or recent use (30 days) of injected or oral corticosteroids Pregnant or lactating women A history or clinical signs of hypertension (BP > 150mmHg systolic / 100mmHg diastolic) A history or clinical signs of hypotension (BP <90 mmHg systolic / 50mmHg diastolic) A history of cardiovascular or cerebrovascular disease A history of psychiatric disease or substance abuse A medical history or clinical signs of disease that according to investigator would preclude participation in the study

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

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PACAP-38 infusion<br>According to main hypothesis PACAP-38 is expected to induce headache. PACAP-38 causes marked vasodilation visible to investigator. PACAP38 (10 pmol/kg/min) is infused over 20 minutes, patients are observed before (15 minutes), during and after (70 minutes) infusion. Blood samples are drawn at fixed time-points. | Other: Evaluation of headache inducing capabilities of PACAP38<br>* We wish to investigate the headache inducing capabilities of PACAP-38, a vasoactive peptide, over a 20 minute infusion. As PACAP-38 casues visible vasodilation, another vasoactive peptide, called VIP will be used as an active comparator.<br>|
| Active Comparator: VIP infusion<br>According to main hypothesis VIP is not expected to induce headache. VIP also causes marked vasodilation visible to investigator, which is why VIP is chosen as an active comparator. VIP (10 pmol/kg/min) is infused over 20 minutes. VIP is infused over 20 minutes, patients are observed before (15 minutes), during and after (70 minutes) infusion. Blood samples are drawn at fixed time-points. | Other: Evaluation of headache inducing capabilities of PACAP38<br>* We wish to investigate the headache inducing capabilities of PACAP-38, a vasoactive peptide, over a 20 minute infusion. As PACAP-38 casues visible vasodilation, another vasoactive peptide, called VIP will be used as an active comparator.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Headache | Difference in incidence of headache within 90 minutes of infusion between PACAP-38 infusion and VIP infusion | 90 minutes | 
| Plasma/serum levels of PACAP-38, VIP, CGRP, Histamine, Tryptase and NSE | Changes in plasma/serum concentrations of the following markers after infusion of PACAP-38 and VIP: PACAP-38, VIP, CGRP, Histamine, Tryptase, NSE | 90 minutes | 
| Plasma/serum levels of PACAP-38, VIP, CGRP, Histamine, Tryptase and NSE after infusion | Difference in plasma/serum concentrations of the following markers after infusion of PACAP-38 and VIP: PACAP-38, VIP, CGRP, Histamine, Tryptase, NSE between patients with induced cluster headache and patients without headache | 90 minutes | 
| Plasma/serum levels of PACAP-38, VIP, CGRP, Histamine, Tryptase and NSE at baseline | Difference in plasma/serum concentrations of the following markers at baseline: PACAP-38, VIP, CGRP, Histamine, Tryptase, NSE between patients with episodic cluster headache in remission, episodic cluster headache in cluster, and chronic cluster headache | 90 minutes | 
| Headache intensity | Difference in AUD for headache intensity scores (0-90 minutes) | 90 minutes | 
| Time to headache peak | Difference in time to peak headache between PACAP-38 day and VIP day | 90 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mean arterial blood pressure | Difference in area under the curve (AUC) for mean arterial pressure (based on systolic and diastolic measurements) and heart rate during experiment | 90 minutes | 
| Plasma/serum levels of PACAP-38, VIP, CGRP, Histamine, Tryptase and NSE | Difference in serum/plasma levels of PACAP-38, VIP, CGRP, Histamine, Tryptase and NSE at baseline in patients who develop a cluster headache attack compared to those who do not | Baseline |