NCT02309606

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
56

participants targeted

Target at P25-P50 for all trials

Timeline
Completed

Started Jan 2015

Typical duration for all trials

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 2, 2014

Completed
3 days until next milestone

First Posted

Study publicly available on registry

December 5, 2014

Completed
27 days until next milestone

Study Start

First participant enrolled

January 1, 2015

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2017

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2017

Completed
Last Updated

January 31, 2018

Status Verified

January 1, 2018

Enrollment Period

2.6 years

First QC Date

December 2, 2014

Last Update Submit

January 30, 2018

Conditions

Migraine Without Aura

Outcome Measures

Primary Outcomes (5)

  • 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

Study Arms (3)

Migraine without aura

Migraine patients suffering from migraine 0-4 days per month.

Other: PET scan with 5-HT receptor ligands

Healthy controls

Healthy controls with no history of migraine or other primary headaches.

Other: PET scan with 5-HT receptor ligands

Chronic migraine

Migraine patients with chronic migraine

Other: PET scan with 5-HT receptor ligands

Interventions

PET scan with 5-HT receptor ligandsOTHER

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 migraineHealthy controlsMigraine without aura

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Migraine patients and healthy controls.

You may qualify if:

  • Written informed consent
  • Migraine without aura according to the International Headache Society (IHS) 0-4 days per month
  • The migraine is treatable with sumatriptan
  • Do not suffer from migraine according to IHS
  • Do not have any first degree relatives with migraine

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Danish Headache Center, Glostrup Hospital

Glostrup, Copenhagen, 2600, Denmark

Location

MeSH Terms

Conditions

Migraine without Aura

Interventions

Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Migraine DisordersHeadache Disorders, PrimaryHeadache DisordersBrain DiseasesCentral Nervous System DiseasesNervous System Diseases

Intervention Hierarchy (Ancestors)

Spectrum AnalysisChemistry Techniques, AnalyticalInvestigative Techniques

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
CROSS SECTIONAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Medical Doctor

Study Record Dates

First Submitted

December 2, 2014

First Posted

December 5, 2014

Study Start

January 1, 2015

Primary Completion

August 1, 2017

Study Completion

December 1, 2017

Last Updated

January 31, 2018

Record last verified: 2018-01

Locations

DK(1)