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

Migraine Without Aura Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02309606
• Other study ID #: H-6-2014-057
• Status: Completed
• Phase: N/A
• First received: December 2, 2014
• Last updated: January 30, 2018
• Start date: January 2015
• Est. completion date: December 2017

Study information

• Verified date: January 2018
• Source: Danish Headache Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: December 2017
• Est. primary completion date: August 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Migraine Disorders
• Migraine without Aura

Intervention

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.

Locations

Country	Name	City	State
Denmark	Danish Headache Center, Glostrup Hospital	Glostrup, Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
Danish Headache Center

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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