PACAP38 Induced Headache and Rosacea-like Symptoms in Patients With Rosacea

Investigation of PACAP38-induced Headache and Rosacea-like Symptoms in Patients With Rosacea

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

Study Overview

• Status: Completed
• Conditions: Rosacea
• Intervention / Treatment: Drug: Imigran; Other: Isotonic Saline

Detailed Description

Pituitary adenylate cyclase-activating peptide-38 (PACAP38) plays a role in rosacea pathophysiology. Infusions of PACAP38 can trigger migraine-like attacks in migraine patients. PACAP38 also induces flushing which may imitate rosacea-like flushing. We are investigating whether the flushing after PACAP38 resembles rosacea-like flushing, and whether treatment with sumatriptan has an effect on the headache and flushing effects of PACAP38.

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

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• diagnosed with rosacea
• 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 Assignment
• 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 Imigrane 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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of headache and migraine	Incidence of PACAP38-induced headache and migraine-like attacks in patients with rosacea measured by numerical rating scale for pain from 0 ("no pain") to 10 ("worst pain imaginable") and international classification for migraine.	From 0 to 24 hours after infusion
Effect of sumatriptan	Severity of PACAP38-induced headache after pretreatment with sumatriptan in rosacea patients measured by numerical rating scale for pain from 0 ("no pain") to 10 ("worst pain imaginable")	From 0 to 24 hours after infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of flushing	Severity of PACAP38-induced flushing with and without sumatriptan-treatment measured by laser doppler flowmetry	From 0 to 4 hours after infusion
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

Collaborators and Investigators

• Sponsor: Danish Headache Center
• Investigators: Principal Investigator: Messoud Ashina, MD,PhD,DMSc, Professor

Publications and helpful links

General Publications

• Wienholtz NKF, Christensen CE, Coskun H, Zhang DG, Ghanizada H, Egeberg A, Thyssen JP, Ashina M. Infusion of Pituitary Adenylate Cyclase-Activating Polypeptide-38 in Patients with Rosacea Induces Flushing and Facial Edema that Can Be Attenuated by Sumatriptan. J Invest Dermatol. 2021 Jul;141(7):1687-1698. doi: 10.1016/j.jid.2021.02.002. Epub 2021 Feb 16.

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2018
• Primary Completion (Actual): December 19, 2019
• Study Completion (Actual): December 19, 2019

Study Registration Dates

• First Submitted: March 4, 2019
• First Submitted That Met QC Criteria: March 15, 2019
• First Posted (Actual): March 18, 2019

Study Record Updates

• Last Update Posted (Actual): March 26, 2020
• Last Update Submitted That Met QC Criteria: March 25, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Pain; Neurologic Manifestations; Rosacea; Headache; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Serotonin Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Vasoconstrictor Agents; Sumatriptan
• Other Study ID Numbers: RosMigExperiment

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