1H Magnetic Resonance Spectroscopy in Migraine Patients

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

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

Study Overview

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

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 Type: Interventional
• Enrollment (Actual): 39
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Collaborators: European Commission; Netherlands Organisation for Scientific Research

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2015
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: December 30, 2019
• First Submitted That Met QC Criteria: January 5, 2020
• First Posted (Actual): January 7, 2020

Study Record Updates

• Last Update Posted (Actual): January 7, 2020
• Last Update Submitted That Met QC Criteria: January 5, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Pain; Neurologic Manifestations; Disease; Nervous System Diseases; Brain Diseases; Migraine Disorders; Headache; Headache Disorders; Migraine without Aura; Central Nervous System Diseases; Headache Disorders, Primary; Vasodilator Agents; Nitroglycerin
• Other Study ID Numbers: P07079.6

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No