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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
Sponsored by
Danish Headache Center
About
Eligibility
Locations
Arms
Outcomes
Full info

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

First Posted
January 15, 2019
Last Updated
January 22, 2019
Sponsor
Danish Headache Center
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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
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

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
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.
Arm Title
VIP infusion
Arm Type
Active Comparator
Arm Description
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.
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
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
Time Frame
90 minutes
Title
Plasma/serum levels of PACAP-38, VIP, CGRP, Histamine, Tryptase and NSE at baseline
Description
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
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
No
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
Email
agneta.henriette.snoer.02@regionh.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Luise Vollsen, MD
Phone
+45 25732284
Email
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
Email
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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