PACAP38 Induced Headache and Rosacea-like Symptoms in Patients With Rosacea
Primary Purpose
Rosacea
Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Imigran
Isotonic Saline
Sponsored by
About this trial
This is an interventional treatment trial for Rosacea
Eligibility Criteria
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
Sites / Locations
- DanishHC
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
PACAP38 + Imigran
PACAP38 + Isotonic Saline
Arm Description
Pituitary adenylate cyclase-activating peptide-38 infusion (10 picomol/kg/min) for 20 mins AND Imigrane infusion (0.4 mg/min) for 10 mins
Pituitary adenylate cyclase-activating peptide-38 infusion (10 picomol/kg/min) for 20 mins AND Isotonic saline for 10 mins (placebo)
Outcomes
Primary Outcome Measures
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.
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")
Secondary Outcome Measures
Severity of flushing
Severity of PACAP38-induced flushing with and without sumatriptan-treatment measured by laser doppler flowmetry
Facial temperature
PACAP38-induced temperature changes with and without sumatriptan-treatment measured by infrared thermography
Superficial temporal artery diameter
Superficial temporal artery diameter after PACAP38 with and without sumatriptan-treatment measured by ultrasound
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03878784
Brief Title
PACAP38 Induced Headache and Rosacea-like Symptoms in Patients With Rosacea
Official Title
Investigation of PACAP38-induced Headache and Rosacea-like Symptoms in Patients With Rosacea
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
November 12, 2018 (Actual)
Primary Completion Date
December 19, 2019 (Actual)
Study Completion Date
December 19, 2019 (Actual)
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
Yes
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rosacea
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Masking Description
Double-blind
Allocation
Randomized
Enrollment
38 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PACAP38 + Imigran
Arm Type
Active Comparator
Arm Description
Pituitary adenylate cyclase-activating peptide-38 infusion (10 picomol/kg/min) for 20 mins
AND
Imigrane infusion (0.4 mg/min) for 10 mins
Arm Title
PACAP38 + Isotonic Saline
Arm Type
Placebo Comparator
Arm Description
Pituitary adenylate cyclase-activating peptide-38 infusion (10 picomol/kg/min) for 20 mins
AND
Isotonic saline for 10 mins (placebo)
Intervention Type
Drug
Intervention Name(s)
Imigran
Other Intervention Name(s)
Sumatriptan
Intervention Description
All patients will undergo this intervention on one of two study days
Intervention Type
Other
Intervention Name(s)
Isotonic Saline
Intervention Description
All patients will undergo this intervention on one of two study days
Primary Outcome Measure Information:
Title
Incidence of headache and migraine
Description
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.
Time Frame
From 0 to 24 hours after infusion
Title
Effect of sumatriptan
Description
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")
Time Frame
From 0 to 24 hours after infusion
Secondary Outcome Measure Information:
Title
Severity of flushing
Description
Severity of PACAP38-induced flushing with and without sumatriptan-treatment measured by laser doppler flowmetry
Time Frame
From 0 to 4 hours after infusion
Title
Facial temperature
Description
PACAP38-induced temperature changes with and without sumatriptan-treatment measured by infrared thermography
Time Frame
From 0 to 4 hours after infusion
Title
Superficial temporal artery diameter
Description
Superficial temporal artery diameter after PACAP38 with and without sumatriptan-treatment measured by ultrasound
Time Frame
From 0 to 4 hours after infusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Messoud Ashina, MD,PhD,DMSc
Organizational Affiliation
Professor
Official's Role
Principal Investigator
Facility Information:
Facility Name
DanishHC
City
Glostrup
ZIP/Postal Code
DK-2600
Country
Denmark
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
33600826
Citation
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.
Results Reference
derived
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PACAP38 Induced Headache and Rosacea-like Symptoms in Patients With Rosacea
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