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PACAP-38 Infusion in Patients With Cluster Headache

Primary Purpose

Cluster Headache

Status

Unknown status

Phase

Not Applicable

Locations

Denmark

Study Type

Interventional

Intervention

Evaluation of headache inducing capabilities of PACAP38

About this trial

This is an interventional basic science trial for Cluster Headache

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Danish Headache CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

PACAP-38 infusion

VIP infusion

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Headache

Difference in incidence of headache within 90 minutes of infusion between PACAP-38 infusion and VIP infusion

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

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

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

Headache intensity

Difference in AUD for headache intensity scores (0-90 minutes)

Time to headache peak

Difference in time to peak headache between PACAP-38 day and VIP day

Secondary Outcome Measures

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

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

Full Information

NCT ID

NCT03814226

First Posted

January 15, 2019

Last Updated

January 22, 2019

Sponsor

Danish Headache Center

1. Study Identification

Unique Protocol Identification Number

NCT03814226

Brief Title

PACAP-38 Infusion in Patients With Cluster Headache

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2019

Overall Recruitment Status

Unknown status

Study Start Date

January 1, 2018 (Actual)

Primary Completion Date

January 1, 2020 (Anticipated)

Study Completion Date

May 5, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Danish Headache Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cluster Headache

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

Investigator

Allocation

Randomized

Enrollment

45 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

PACAP-38 infusion

Arm Type

Experimental

Arm Description

Arm Title

VIP infusion

Arm Type

Active Comparator

Arm Description

Intervention Type

Other

Intervention Name(s)

Evaluation of headache inducing capabilities of PACAP38

Intervention Description

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.

Primary Outcome Measure Information:

Title

Headache

Description

Difference in incidence of headache within 90 minutes of infusion between PACAP-38 infusion and VIP infusion

Time Frame

90 minutes

Title

Plasma/serum levels of PACAP-38, VIP, CGRP, Histamine, Tryptase and NSE

Description

Changes in plasma/serum concentrations of the following markers after infusion of PACAP-38 and VIP: PACAP-38, VIP, CGRP, Histamine, Tryptase, NSE

Time Frame

90 minutes

Title

Plasma/serum levels of PACAP-38, VIP, CGRP, Histamine, Tryptase and NSE after infusion

Description

Time Frame

90 minutes

Title

Plasma/serum levels of PACAP-38, VIP, CGRP, Histamine, Tryptase and NSE at baseline

Description

Time Frame

90 minutes

Title

Headache intensity

Description

Difference in AUD for headache intensity scores (0-90 minutes)

Time Frame

90 minutes

Title

Time to headache peak

Description

Difference in time to peak headache between PACAP-38 day and VIP day

Time Frame

90 minutes

Secondary Outcome Measure Information:

Title

Change in mean arterial blood pressure

Description

Difference in area under the curve (AUC) for mean arterial pressure (based on systolic and diastolic measurements) and heart rate during experiment

Time Frame

90 minutes

Title

Plasma/serum levels of PACAP-38, VIP, CGRP, Histamine, Tryptase and NSE

Description

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

Time Frame

Baseline

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Agneta Snoer, MD

Phone

+ 45 26274040

agneta.henriette.snoer.02@regionh.dk

First Name & Middle Initial & Last Name or Official Title & Degree

Luise Vollsen, MD

Phone

+45 25732284

luisevollsen@gmail.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Messoud Ashina, Professor

Organizational Affiliation

Danish Headache Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Danish Headache Center

City

Glostrup

ZIP/Postal Code

2620

Country

Denmark

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Agneta Snoer, MD

Phone

+ 45 26274040

agneta.henriette.snoer.02@regionh.dk

First Name & Middle Initial & Last Name & Degree

Anne Luise Vollesen, MD

First Name & Middle Initial & Last Name & Degree

Messoud Ashina, DMSc

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

34822741

Citation

Pellesi L, Chaudhry BA, Vollesen ALH, Snoer AH, Baumann K, Skov PS, Jensen RH, Ashina M. PACAP38- and VIP-induced cluster headache attacks are not associated with changes of plasma CGRP or markers of mast cell activation. Cephalalgia. 2022 Jul;42(8):687-695. doi: 10.1177/03331024211056248. Epub 2021 Nov 25. Erratum In: Cephalalgia. 2022 May 12;:3331024221076702.

Results Reference

derived

PubMed Identifier

32962406

Citation

Vollesen ALH, Snoer A, Chaudhry B, Petersen AS, Hagedorn A, Hoffmann J, Jensen RH, Ashina M. The effect of pituitary adenylate cyclase-activating peptide-38 and vasoactive intestinal peptide in cluster headache. Cephalalgia. 2020 Nov;40(13):1474-1488. doi: 10.1177/0333102420940689. Epub 2020 Sep 22.

Results Reference

derived

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PACAP-38 Infusion in Patients With Cluster Headache

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