Prediction of WMH in Migraine Using a BOLD-CVR Map

Research of Brain White Matter Hyperintensity in Migraine Using a Cerebrovascular Reactivity Mapping Based on BOLD MRI

Brain white matter hyperintensities (WMHs) are prevalent in migraineurs, of which the mechanism is still unclear. The investigators aimed to test the spatial association between areas with reduced cerebrovascular reactivity (CVR) to hypercapnic stimuli and consequent development of WMHs.

Study Overview

• Status: Unknown
• Conditions: Migraine
• Intervention / Treatment: Diagnostic test: BOLD MRI

Detailed Description

A whole-brain map of CVR will be created in patients with migraine and normal controls. Hypercapnic stimuli for CVR will be delivered by prospective end-tidal CO2 targeting device. Hemodynamic responses will be determined by BOLD signal changes using fMRI. WMHs will be determined by high-resolution 3D FLAIR imaging. Patients and controls will undergo serial MRIs with 1 year interval. Associations between areas of reduced CVR and consequent WMH development will be tested in both patients and controls.

• Study Type: Observational
• Enrollment (Actual): 74

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Controls and migraineurs who visited to a single university hospital

Description

Inclusion Criteria:

1. Migraineurs(patients) :

   • age 18-50 years
   • migraine with or without aura as defined by the third edition of the International Classification of Headache Disorders (ICHD-3 beta)
   • migraine duration > 6 months
   • episodic migraine feature headache (< 15 attacks/m)
   • not any preventive medications for migraine

2. Control:

   • age 18-50 years
   • no headache disorder requiring painkillers within the past year
   • no more than moderate intensity of headache within the past year
   • no headache disorder other than Infrequent episodic tension-type headache as defined by the ICHD-3 beta

Exclusion criteria:

• chronic migraine within last month (≥15 attacks/m)
• medication overuse headache as defined by ICHD-3 beta
• other comorbid disease that may affect vascular function (Hypertension, diabetes, hyperlipidemia, cerebral infarction, smoking etc)
• can not breath 20 L for 1 minute because of basal cardiopulmonary disease (chronic obstructive pulmonary disease, heart failure etc)
• a disease that can be exacerbated by elevated PCO2 in blood (Interstitial lung disease, amyotrophic lateral sclerosis etc)
• predicted to be unable to write the headache diary due to cognitive decline
• contraindications to MRI
• pregnancy
• refusal to informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Control; Normal controls without headaches will undergo BOLD MRI with prospective CO2 targeting	Diagnostic test: BOLD MRI; Prospective End-tidal targeting RespirAct device(A specially designed gas blender and sequential rebreathing circuit) will be used to implement the gas targeting method which involves precise elevations in End-tidal PCO2 while maintaining a fixed End-tidal PO2; BOLD MR images will be obtained by using a T2*-weighted two-dimensional gradient-echo sequence with echoplanar readout.
Migraineurs; Patients diagnosed with migraine based on the ICHD-3 beta will undergo BOLD MRI with prospective CO2 targeting	Diagnostic test: BOLD MRI; Prospective End-tidal targeting RespirAct device(A specially designed gas blender and sequential rebreathing circuit) will be used to implement the gas targeting method which involves precise elevations in End-tidal PCO2 while maintaining a fixed End-tidal PO2; BOLD MR images will be obtained by using a T2*-weighted two-dimensional gradient-echo sequence with echoplanar readout.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CVR association with WMH development	The investigators will obtain a CVR map using BOLD MR signal in the first year of study and also obtain changes in WMH during 2 years of follow-up period in patients and controls, respectively. Then the investigators will test whether CVR-map predicts consequent WMH development in patients and controls, respectively.	1-year follow-up (2nd year)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spatial pattern of CVR	The investigators will obtain a CVR map for each voxel using BOLD MR signal in response to % increase in EtCO2 respectively in patients and controls. Spatial pattern of CVR will be compared between patients and controls.	baseline(1st year)

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Collaborators: National Research Foundation of Korea
• Investigators: Study Director: Mi Ji Lee, MD, Samsung Medical Center, Sungkyunkwan University School of Medicine

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 13, 2018
• Primary Completion (ANTICIPATED): February 28, 2020
• Study Completion (ANTICIPATED): February 28, 2020

Study Registration Dates

• First Submitted: March 28, 2018
• First Submitted That Met QC Criteria: April 4, 2018
• First Posted (ACTUAL): April 11, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 10, 2019
• Last Update Submitted That Met QC Criteria: April 9, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Cerebrovascular reactivity; White matter hyperintensity
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: 2017-04-049

Drug and device information, study documents

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