Investigation of Vasodilation and Intensity of Headache Triggered by Glucagon Like Peptide-1 in Humans

Study Overview
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Brief Summary
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Studying glucagon-like peptide-1 (GLP-1) induced vasodilatory effects on extra - and intracerebral arteries and headache in healthy volunteers and migraine patients without aura.

Detailed Description
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The purpose of this study is to examine the association between vasodilation and intensity of headache triggered by glucagon-like peptide 1 (GLP-1) in healthy volunteers and migraine patients without aura.

Official Title
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Investigation of Vasodilation and Intensity of Headache Triggered by Glucagon-like Peptide-1 in Healthy Volunteers and Migraine Patients

Conditions
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Headache, Migraine

Intervention / Treatment
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* Other: GLP-1 peptide
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Criteria for the healthy volunteers group Inclusion Criteria: Healthy men/women. Age 18 to 60 years old. Weight 50 to 100 kg. Exclusion Criteria: Tension headache more than 5 days a month in the preceding year. All other primary headache types. Headache on the examination day or within 48 hours before infusion of the study drug. Smoking. Daily intake of medicine of any kind except for peroral contraceptives. Women, who on the day of examination is 2 days before or 3 days from the first day of bleeding. Hypertension or hypotension. Coronary heart disease of any kind, as well as cerebrovascular disease. Pulmonary disease. Allergy to contents in the study drug. Psychiatric disease or substance abuse. Disease of any kind which the examining doctor deems relevant for participation in the study. Renouncing the right to information concerning own health. Criteria for the migraine patients group Inclusion Criteria: Migraine patients, who fulfill the ICHD-3 criteria for migraine without aura. Age 18 to 60 years old. Weight 50 to 100 kg. Exclusion Criteria: Tension headache more than 5 days a month in the preceding year. All other primary headache types. Headache on the examination day or within 48 hours before infusion of the study drug. Smoking. Daily intake of medicine of any kind except for peroral contraceptives. Women, who on the day of examination is 2 days before or 3 days from the first day of bleeding. Hypertension or hypotension. Coronary heart disease of any kind, as well as cerebrovascular disease. Pulmonary disease. Allergy to contents in the study drug. Psychiatric disease or substance abuse. Disease of any kind which the examining doctor deems relevant for participation in the study. Renouncing the right to information concerning own health.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Phase one: In a randomized, single-blind, multiple-ascending-dose finding pilot study we investigate the safety and tolerability of GLP-1 on three healthy volunteers. The following GLP-1 doses will be given intravenously ( 1.5, 2.0 and 2.5 picomol/kg/min) over 20 min. The dose with considerable dilatory effect will be chosen for main study. Phase 2 and 3:The study is a double-blinded, placebo-controlled, randomized crossover study. It involves two arms, GLP-1 and placebo. Each participant will in a randomized order receive placebo or GLP-1 intravenous infusion over 20 min on the two experiment days. The study consists of two separate substudies, one for healthy volunteers and one for migraine patients. The substudies are otherwise identical.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: GLP-1<br>Receive intravenous infusion of GLP-1. | Other: GLP-1 peptide<br>* Receive intravenous infusion of GLP-1. The dosage will be determined after a dose finding pilot study.<br>|
| Placebo Comparator: Placebo<br>Receive intravenous infusion of saline. | Other: Placebo<br>* Receive intravenous infusion saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vasodilation | Difference in circumference (in millimeter) of intra - and extracranial blood vessels before and after GLP-1 or placebo infusion, measured by transcranial doppler and ultrasound (Derma scan) at 10 specific time points (-10, 10, 20, 30, 40, 50, 60, 80, 100, and 120 minutes) | 120 minutes | 
| Headache intensity | Headache intensity will be measured using Numerical rating scale (NRS) from ( 0 to 10 ) | 12 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| blood pressure | Blood pressure (systolic and diastolic) in mmhg will be measured every 10 minutes | 120 minutes | 
| Facial skin perfusion | Non-invasive measuring of facial skin perfusion by laser speckle contrast imager. | 120 minutes | 
| Heart rate | heart rate will be measured every 10 minutes | 120 minutes | 
| Plasma glucose | Plasma glucose will be measured using (mmol/L) a ABL Radiometer, Denmark Blood-gas analyser | 120 minutes |