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

Completed

• Conditions: Migraine Without Aura
• Interventions: Other: PET scan with 5-HT receptor ligands

• Registration Number: NCT02309606
• Lead Sponsor: Danish Headache Center

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-12-02
• Study First Submitted QC: 2014-12-04
• Study First Posted: 2014-12-05
• Study Start: 2015-01
• Primary Completion: 2017-08
• Study Completion: 2017-12
• Status Verified: 2018-01
• Last Update Submitted: 2018-01-30
• Last Update Posted: 2018-01-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 56

Inclusion Criteria

Not provided

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Chronic migraine	PET scan with 5-HT receptor ligands	Migraine patients with chronic migraine
Migraine without aura	PET scan with 5-HT receptor ligands	Migraine patients suffering from migraine 0-4 days per month.
Healthy controls	PET scan with 5-HT receptor ligands	Healthy controls with no history of migraine or other primary headaches.

Primary Outcome Measures

Name	Time	Method
Differences in binding of the 5-HT4 radioligand	Up to 1 year	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.
Differences in binding of the 5-HT1B radioligand	Up to 1 year	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
Correlation with migraine frequency and 5-HT4 receptor binding	Up to 1 year	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

Trial Locations

Locations (1)

Danish Headache Center, Glostrup Hospital; 🇩🇰 Glostrup, Copenhagen, Denmark