NCT03814226

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
45

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Jan 2018

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2018

Completed
1 year until next milestone

First Submitted

Initial submission to the registry

January 15, 2019

Completed
8 days until next milestone

First Posted

Study publicly available on registry

January 23, 2019

Completed
11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2020

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 5, 2020

Completed
Last Updated

January 23, 2019

Status Verified

January 1, 2019

Enrollment Period

2 years

First QC Date

January 15, 2019

Last Update Submit

January 22, 2019

Conditions

Cluster Headache

Outcome Measures

Primary Outcomes (6)

  • 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 Outcomes (2)

  • Change in mean arterial blood pressure

    90 minutes

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

    Baseline

Study Arms (2)

PACAP-38 infusion

EXPERIMENTAL

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

VIP infusion

ACTIVE COMPARATOR

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

Interventions

Evaluation of headache inducing capabilities of PACAP38OTHER

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.

PACAP-38 infusionVIP infusion

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Danish Headache Center

Glostrup Municipality, 2620, Denmark

RECRUITING

Related Publications (3)

  • Deligianni C, Pellesi L, Chaudhry BA, Haulund Vollesen AL, Snoer AH, Hannibal J, Jensen RH, Ashina M. Plasma levels of VIP are not elevated during PACAP- and VIP-induced cluster headache attacks: an exploratory study. Front Neurol. 2023 Apr 18;14:1135246. doi: 10.3389/fneur.2023.1135246. eCollection 2023.

    PMID: 37143998DERIVED

  • 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.

    PMID: 34822741DERIVED

  • 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.

    PMID: 32962406DERIVED

MeSH Terms

Conditions

Cluster Headache

Condition Hierarchy (Ancestors)

Trigeminal Autonomic CephalalgiasHeadache Disorders, PrimaryHeadache DisordersBrain DiseasesCentral Nervous System DiseasesNervous System Diseases

Study Officials

  • Messoud Ashina, Professor

    Danish Headache Center

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Agneta Snoer, MD

CONTACT

+ 45 26274040agneta.henriette.snoer.02@regionh.dk

Luise Vollsen, MD

CONTACT

+45 25732284luisevollsen@gmail.com

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
INVESTIGATOR
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, PhD Student, Investigator

Study Record Dates

First Submitted

January 15, 2019

First Posted

January 23, 2019

Study Start

January 1, 2018

Primary Completion

January 1, 2020

Study Completion

May 5, 2020

Last Updated

January 23, 2019

Record last verified: 2019-01

Locations

DK(1)