1H Magnetic Resonance Spectroscopy in Migraine Patients

Study Overview
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Brief Summary
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To investigate the glutaminergic system in the onset of migraine-like attacks.

Detailed Description
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Glyceryl trinitrate infusion (GTN) is used to provoke migraine-like attacks in female migraine without aura patients. Apart from migraine without aura patients healthy female controls are also included as a control group. Over the course of a single day these females (migraineurs and healthy controls) were scanned three times on fixed time slots: before GTN infusion (baseline), 90 minutes and 270 minutes after start of GTN infusion. Scans are acquired on a 7 tesla scanner (Philips, Cleveland, USA) on software release 3 using a 32 channel receive array using single-volume proton magnetic resonance spectroscopy (1H MRS) with a volume of interest in the visual cortex glutamate, in which glutamate, GABA and other metabolites will be assessed. The primary endpoint; glutamate level changes towards the pre-ictal and ictal state with other metabolite (e.g. glutamine and GABA) changes as secondary endpoints.

Official Title
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Glutamate Concentrations in the Brain Over the Course of a Migraine-like Attack

Conditions
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Migraine Disorders, Migraine Without Aura, Headache Disorders, Primary, Headache Disorders, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases

Intervention / Treatment
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* Drug: Glyceryl trinitrate (I.V. infusion 0.5 µg/kg/min over 20 min)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with migraine without aura according to the International Classification of Headache Disorders (ICHD)-3 beta criteria from 2013. At least one migraine attack per month in the preceding six months Exclusion Criteria: Other neurological disorders apart from migraine Chronic medication apart from oral contraceptives Migraine with aura Chronic migraine with 15 or more headache days per month/with 8 or more migraine days per month Medication-overuse headache (ICHD-3 beta criteria) Women who are breastfeeding, pregnant, or planning to become pregnant Contra-indications for 7 tesla MRI scanner Contra-indications for GTN administration (e.g. nitrate allergy, heart condition) Healthy controls (with no first degree relative with migraine or trigeminal autonomic cephalalgia)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

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: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Migraine without aura subjects<br>Drug: Glyceryl trinitrate (GTN) | Drug: Glyceryl trinitrate (I.V. infusion 0.5 µg/kg/min over 20 min)<br> <br> |
| Other: Healthy subjects<br>Drug: Glyceryl trinitrate (GTN) | Drug: Glyceryl trinitrate (I.V. infusion 0.5 µg/kg/min over 20 min)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glutamate | Changes in glutamate level | From baseline towards the pre-ictal (assessed at 90 and/or 270 minutes after GTN depending on clinical condition) and ictal (assessed at 90 and/or 270 minutes after GTN depending on clinical condition) state | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glutamine | Changes in glutamine level | From baseline towards the pre-ictal (assessed at 90 and/or 270 minutes after GTN depending on clinical condition) and ictal (assessed at 90 and/or 270 minutes after GTN depending on clinical condition) state | 
| GABA | Changes in GABA level | From baseline towards the pre-ictal (assessed at 90 and/or 270 minutes after GTN depending on clinical condition) and ictal (assessed at 90 and/or 270 minutes after GTN depending on clinical condition) state | 
| N-acetylaspartate | Changes in N-acetylaspartate level | From baseline towards the pre-ictal (assessed at 90 and/or 270 minutes after GTN depending on clinical condition) and ictal (assessed at 90 and/or 270 minutes after GTN depending on clinical condition) state | 
| Phosphoethanolamine | Changes in phosphoethanolamine level | From baseline towards the pre-ictal (assessed at 90 and/or 270 minutes after GTN depending on clinical condition) and ictal (assessed at 90 and/or 270 minutes after GTN depending on clinical condition) state | 
| Myo-inositol | Changes in myo-inositol level | From baseline towards the pre-ictal (assessed at 90 and/or 270 minutes after GTN depending on clinical condition) and ictal (assessed at 90 and/or 270 minutes after GTN depending on clinical condition) state | 
| Glutathione | Changes in glutathione level | From baseline towards the pre-ictal (assessed at 90 and/or 270 minutes after GTN depending on clinical condition) and ictal (assessed at 90 and/or 270 minutes after GTN depending on clinical condition) state | 
| Aspartate | Changes in aspartate level | From baseline towards the pre-ictal (assessed at 90 and/or 270 minutes after GTN depending on clinical condition) and ictal (assessed at 90 and/or 270 minutes after GTN depending on clinical condition) state | 
| Creatine | Changes in creatine level | From baseline towards the pre-ictal (assessed at 90 and/or 270 minutes after GTN depending on clinical condition) and ictal (assessed at 90 and/or 270 minutes after GTN depending on clinical condition) state | 
| Choline | Changes in choline level | From baseline towards the pre-ictal (assessed at 90 and/or 270 minutes after GTN depending on clinical condition) and ictal (assessed at 90 and/or 270 minutes after GTN depending on clinical condition) state |