The Role of Inflammation and Vasodilatation in PACAP38-induced Headache Using MRI on Healthy Subjects

Studying Pituitary adenylate cyclase-activating peptide 38 (PACAP38) induced headache effects on extra- and intracerebral arteries and pre-posttreated by sumatriptan and ketorolac assessed by magnetic resonance imaging (MRI) on healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Headache
• Intervention / Treatment: Other: Sumatriptan; Other: Ketorolac

Detailed Description

The purpose of this research project is to investigate the importance of blood vessel (vasodilatation), vessel wall inflammation and blood flow in arteries of headaches triggered by PACAP38 and for headache treated with sumatriptan (migraine medicine) and ketorolac (NSAID). In addition, we will investigate headache-related changes in the brain's network connectivity.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Glostrup, Denmark, 2600
    • Danish Headache Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy volunteers
• Aged 18-50
• 50-100 kg

Exclusion Criteria:

• Tension type headache more than 5 dag /month
• Other primary headaches
• Daily medication except contraceptives
• Drug taken within 4 times the half-life for the specific drug except contraceptives
• Pregnant or lactating women
• Exposure to radiation within the last year
• Headache within the last 24 hours before start of trial
• Hypertension
• Hypotension
• Respiratory or cardiac disease
• Primary relatives with current or previous migraine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Sumatriptan; Sumatriptan 4 mg/mL I.V will be administrated over 10 min	Other: Sumatriptan; Receive intravenous infusion of sumatriptan
ACTIVE_COMPARATOR: Ketorolac; Ketorolac 30 mg/mL I.V will be administrated over 10 min	Other: Ketorolac; Receive intravenous infusion of ketorolac

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intra-extra cerebral arteries vasodilatation	PACAP38 vasodilatation reverse by sumatriptan but not ketorolac. A single-slab 3D time-of-flight (3D TOF) MRA of extra- and intracranial arteries will be acquired as described in previous studies (Amin et al., 2013, 2014). MRA data will be analyzed by LKEB-MRA vessel wall analysis software program. We will measure the circumference of vessels in millimeter in 4 predefined time points (0, 20, 60 and 110 min)	120 minutes
Headache score	Visual analog Scale	6 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood pressure	vital parameters recorded at hospital phase	2 hours
Headache characteristics	Standard headache questionnaire will be used to record headache localization, nausea, photo and phonophobia.	24 hours
Heart rate	vital parameters recorded at hospital phase	2 hours

Collaborators and Investigators

• Sponsor: Danish Headache Center

Publications and helpful links

General Publications

• Ghanizada H, Al-Karagholi MA, Arngrim N, Morch-Rasmussen M, Metcalf-Clausen M, Larsson HBW, Amin FM, Ashina M. Investigation of sumatriptan and ketorolac trometamol in the human experimental model of headache. J Headache Pain. 2020 Feb 24;21(1):19. doi: 10.1186/s10194-020-01089-3.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2018
• Primary Completion (ACTUAL): August 1, 2019
• Study Completion (ACTUAL): November 25, 2019

Study Registration Dates

• First Submitted: June 28, 2018
• First Submitted That Met QC Criteria: July 12, 2018
• First Posted (ACTUAL): July 13, 2018

Study Record Updates

• Last Update Posted (ACTUAL): January 2, 2020
• Last Update Submitted That Met QC Criteria: December 29, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Pain; Neurologic Manifestations; Inflammation; Headache; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Serotonin Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Vasoconstrictor Agents; Ketorolac; Sumatriptan
• Other Study ID Numbers: H-18008313

Drug and device information, study documents

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