1H Magnetic Resonance Spectroscopy in Migraine Patients

Not Applicable

Completed

• Conditions: Headache Disorders, Primary; Brain Diseases; Migraine Disorders; Migraine Without Aura; Headache Disorders; Nervous System Diseases; Central Nervous System Diseases
• Interventions: Drug: Glyceryl trinitrate (I.V. infusion 0.5 µg/kg/min over 20 min)

• Registration Number: NCT04220606
• Lead Sponsor: Leiden University Medical Center

Brief Summary

To investigate the glutaminergic system in the onset of migraine-like attacks.

Detailed Description

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.

Study Timeline

• Study Start: 2015-04
• Primary Completion: 2016-04
• Study Completion: 2016-04
• Study First Submitted: 2019-12-30
• Status Verified: 2020-01
• Study First Submitted QC: 2020-01-05
• Last Update Submitted: 2020-01-05
• Study First Posted: 2020-01-07
• Last Update Posted: 2020-01-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 39

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Migraine without aura subjects	Glyceryl trinitrate (I.V. infusion 0.5 µg/kg/min over 20 min)	Drug: Glyceryl trinitrate (GTN)
Healthy subjects	Glyceryl trinitrate (I.V. infusion 0.5 µg/kg/min over 20 min)	Drug: Glyceryl trinitrate (GTN)

Primary Outcome Measures

Name	Time	Method
Glutamate	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	Changes in glutamate level

Secondary Outcome Measures

Name	Time	Method
Myo-inositol	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	Changes in myo-inositol level
Glutathione	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	Changes in glutathione level
Aspartate	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	Changes in aspartate level
Creatine	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	Changes in creatine level
Choline	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	Changes in choline level
Glutamine	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	Changes in glutamine level
GABA	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	Changes in GABA level
N-acetylaspartate	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	Changes in N-acetylaspartate level
Phosphoethanolamine	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	Changes in phosphoethanolamine level