PACAP38 Induced Headache, Migraine and Flushing in Patients With Migraine

Investigation of PACAP38 Induced Headache, Migraine and Flushing in Patients With Migraine

The aim is to investigate the incidence of headache, migraine attacks and flushing after pituitary adenylate cyclase-activating peptide-38 (PACAP38) with and without treatment with sumatriptan in patients with migraine

Study Overview

• Status: Completed
• Conditions: Migraine Without Aura
• Intervention / Treatment: Drug: Imigran; Other: Isotonic Saline; Other: Pituitary adenylate cyclase-activating peptide-38

Detailed Description

Pituitary adenylate cyclase-activating peptide-38 (PACAP38) plays a role in migraine pathophysiology. Infusions of PACAP38 can trigger migraine-like attacks in some migraine patients and will induce flushing in all patients. We are investigating whether treatment with sumatriptan has an effect on the PACAP38-induced flushing and on whether headache and migraine is induced.

The purpose of this study is to investigate PACAP38-induced headache and migraine in patients with migraine who have been treated with either sumatriptan or placebo using purpose-developed standardized interview. The study will be conducted with a double-blind, placebo-controlled crossover study design.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Glostrup, Denmark, DK-2600
    • DanishHC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• diagnosis of migraine, according to IHS criteria
• weight between 50 - 100 kilograms
• women in fertile age must not be pregnant and must use adequate contraception

Exclusion Criteria:

• migraine more than 5 days per month in average over the past year
• any primary headache other than migraine, apart from tension-type headache which must be less than 5 days per month
• headache < 48 hours before experimental day
• migraine < 72 hours before each experimental day
• daily / frequent use of any medication apart from contraceptive medication
• use of any drug less than 5 times the half-life of the drug at the time of the experiment
• women who are pregnant or breast-feeding at the time of the experiment
• anamnestic or clinical signs of hypertension (systolic blood pressure > 150 mmHg and/or
• diastolic blood pressure > 100 mmHg) or hypotension (systolic blood pressure < 90 mmHg and/or diastolic blood pressure < 50 mmHg)
• anamnestic or clinical signs of mental illness, or abuse of alcohol / drugs
• patients with glaucoma or prostate hyperplasia
• anamnestic or clinical symptoms of any sort that the investigating doctor deemed unfit for participating in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: PACAP38 + Imigran; Pituitary adenylate cyclase-activating peptide-38 infusion (10 picomol/kg/min) for 20 mins AND Imigran infusion (0.4 mg/min) for 10 mins	Drug: Imigran; All patients will undergo this intervention on one of two study days; Other Names: Sumatriptan; Other: Pituitary adenylate cyclase-activating peptide-38; All patients will undergo this intervention on both study days; Other Names: PACAP38
PLACEBO_COMPARATOR: PACAP38 + Isotonic Saline; Pituitary adenylate cyclase-activating peptide-38 infusion (10 picomol/kg/min) for 20 mins AND Isotonic saline for 10 mins (placebo)	Other: Isotonic Saline; All patients will undergo this intervention on one of two study days; Other: Pituitary adenylate cyclase-activating peptide-38; All patients will undergo this intervention on both study days; Other Names: PACAP38

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of migraine	Incidence of migraine after PACAP38-infusion will be estimated through a standardized interview based on the international headache classification for migraine	From 0 to 12 hours after infusion
Effect of Sumatriptan	Severity of PACAP38-induced headache and migraine after pretreatment with sumatriptan in migraine patients measured by numerical rating scale for pain from 0 ("no pain") to 10 ("worst pain imaginable")	From 0 to 12 hours after infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Facial temperature	PACAP38-induced temperature changes with and without sumatriptan-treatment measured by infrared thermography	From 0 to 4 hours after infusion
Superficial temporal artery diameter	Superficial temporal artery diameter after PACAP38 with and without sumatriptan-treatment measured by ultrasound	From 0 to 4 hours after infusion
Severity of flushing	Facial skin blood flow (flushing) will be measured by laser doppler flowmetry to evaluate the severity of PACAP38-induced flushing with and without sumatriptan-treatment	From 0 to 4 hours after infusion
Severity of headache	Severity of PACAP38-induced headache will be rated on a numerical rating scale for pain from 0 ("no pain") to 10 ("worst pain imaginable")	From 0 to 12 hours after infusion

Collaborators and Investigators

• Sponsor: Danish Headache Center
• Investigators: Study Director: Messoud Ashina, MD,PhD,DMSc, Danish Headache Center

Publications and helpful links

General Publications

• Wienholtz NKF, Christensen CE, Zhang DG, Coskun H, Ghanizada H, Al-Karagholi MA, Hannibal J, Egeberg A, Thyssen JP, Ashina M. Early treatment with sumatriptan prevents PACAP38-induced migraine: A randomised clinical trial. Cephalalgia. 2021 May;41(6):731-748. doi: 10.1177/0333102420975395. Epub 2021 Feb 10.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 17, 2018
• Primary Completion (ACTUAL): December 7, 2019
• Study Completion (ACTUAL): December 7, 2019

Study Registration Dates

• First Submitted: March 15, 2019
• First Submitted That Met QC Criteria: March 15, 2019
• First Posted (ACTUAL): March 19, 2019

Study Record Updates

• Last Update Posted (ACTUAL): June 22, 2020
• Last Update Submitted That Met QC Criteria: June 18, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Skin Manifestations; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Headache; Flushing; Migraine without Aura; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Growth Substances; Serotonin Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Vasoconstrictor Agents; Pituitary Adenylate Cyclase-Activating Polypeptide; Sumatriptan
• Other Study ID Numbers: MigRosExperiment

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No