Investigation of Serotonin Receptor Binding in the Migraine Brain Using Positron Emission Tomography

Migraine affects 16% of the world population and is one of the most disabling of all disorders. It is a complex brain disorder characterized primarily by recurrent headache attacks. The signaling molecule serotonin (5-hydroxytryptamine, 5-HT) has for decades been thought to play a central role in migraine pathophysiology. The most effective class of abortive migraine drugs, the triptans, act on 5-HT receptors. However, the migraine-specific actions of serotonin and the mechanisms of triptans are still unknown. In this project the investigators will use high-resolution positron emission tomography and specific radioligands to investigate the significance of serotonin in migraine. Two newly developed radioligands that are specific for the 5-HT1B and 5-HT4 receptor, respectively, will be applied. To investigate the level and distribution of serotonin in the migraine brain the investigators will compare the binding of these ligands in episodic migraine patients with healthy controls. In addition, the investigators will include chronic migraine patients to evaluate the relation between the level of serotonin in the brain and the frequency of migraine attacks. To investigate the changes in the serotonin level during a migraine attack and the effects of triptans on the central nervous system the investigators will repeat the scans using the 5-HT1B specific ligand during induced migraine attacks and following treatment with sumatriptan. The results from this study will shed light on the role of serotonin in the migraine brain and elucidate the migraine-specific action of triptans. This will improve our understanding of the migraine pathophysiology and, potentially, facilitate the development of more efficient treatment of migraine.

Study Overview

• Status: Completed
• Conditions: Migraine Without Aura
• Intervention / Treatment: Other: PET scan with 5-HT receptor ligands

• Study Type: Observational
• Enrollment (Actual): 56

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Migraine patients and healthy controls.

Description

Inclusion Criteria, both groups:

• Written informed consent

Inclusion Criteria, episodic migraine patients:

• Migraine without aura according to the International Headache Society (IHS) 0-4 days per month
• The migraine is treatable with sumatriptan

Inclusion Criteria, chronic migraine patients: Fulfill IHS criteria for chronic migraine

Inclusion Criteria, healthy controls:

• Do not suffer from migraine according to IHS
• Do not have any first degree relatives with migraine

Exclusion Criteria:

• Tension type headache more than 5 days per month during the last year.
• Tension type headache on the experimental day.
• Any other primary headache disorder
• Migraine 48 hour before and after the experimental day (only episodic migraine patients)
• Use of antimigraine medication or pain-killer on the experimental day before PET
• Pregnant or breastfeeding women.
• Contraindications against MRI.
• History or clinical sign of cardio- or cerebrovascular disease.
• Untreated severe mental disorder or drug abuse.
• Other diseases or disorders interpreted, by the examining doctor, to interfere with participation in the study.
• Not accepting information about potential accidental findings during the experiment.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Migraine without aura; Migraine patients suffering from migraine 0-4 days per month.	Other: PET scan with 5-HT receptor ligands; Interictal episodic migraine patients and healthy controls will be scanned with a 5-HT1B and a 5-HT4 receptor radioligand. Episodic migraine patients will further be scanned during a cilostazol induced migraine attack and after treatment with sumatriptan. Chronic migraine patients will be scanned with only the 5-HT4 receptor radioligand.
Healthy controls; Healthy controls with no history of migraine or other primary headaches.	Other: PET scan with 5-HT receptor ligands; Interictal episodic migraine patients and healthy controls will be scanned with a 5-HT1B and a 5-HT4 receptor radioligand. Episodic migraine patients will further be scanned during a cilostazol induced migraine attack and after treatment with sumatriptan. Chronic migraine patients will be scanned with only the 5-HT4 receptor radioligand.
Chronic migraine; Migraine patients with chronic migraine	Other: PET scan with 5-HT receptor ligands; Interictal episodic migraine patients and healthy controls will be scanned with a 5-HT1B and a 5-HT4 receptor radioligand. Episodic migraine patients will further be scanned during a cilostazol induced migraine attack and after treatment with sumatriptan. Chronic migraine patients will be scanned with only the 5-HT4 receptor radioligand.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in binding of the 5-HT1B radioligand	Differences in bindingpotentials for the 5-HT1B ligand between migraine patients and healthy controls will be assessed using the Simplified Reference Tissue Model.	Up to 1 year
Differences in binding of the 5-HT4 radioligand	Differences in bindingpotentials for the 5-HT4 ligand between migraine patients and healthy controls will be assessed using the Simplified Reference Tissue Model.	Up to 1 year
Differences in binding of the 5-HT4 radioligand	Differences in bindingpotentials for the 5-HT4 ligand between chronic migraine patients and healthy controls and between chronic and episodic migraine patients will be assessed using the Simplified Reference Tissue Model.	Up to 1 year
Correlation with migraine frequency and 5-HT4 receptor binding	Correlations between migraine days and 5-HT4 receptor binding will be investigated using pooled data from episodic and chronic migraine patients on migraine frequency and their 5-HT4 receptor binding potentials assessed using the simplified reference tissue model	Up to 1 year
Differences in binding of the 5-HT1B radioligand	Differences in binding between ictal and interictal binding and between ictal and post-treatment binding in episodic migraine patients will be assessed using the simplified reference tissue model	Up to 1 year

Collaborators and Investigators

• Sponsor: Danish Headache Center

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): August 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: December 2, 2014
• First Submitted That Met QC Criteria: December 4, 2014
• First Posted (Estimate): December 5, 2014

Study Record Updates

• Last Update Posted (Actual): January 31, 2018
• Last Update Submitted That Met QC Criteria: January 30, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Migraine without Aura
• Other Study ID Numbers: H-6-2014-057