Imaging the Migraine Brain Pre- and Post-Erenumab

Migraine Clinical Trial

Official title:

Imaging the Migraine Brain Pre- and Post-Erenumab: an MRI Study to Identify Functional and Structural Changes That Correlate With Patient Improvement

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03773562
• Other study ID #: 18-001497
• Status: Completed
• Phase: Phase 4
• Start date: March 25, 2019
• Est. completion date: June 30, 2022

Study information

• Verified date: December 2023
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Researchers are trying to determine if there is a difference between brain images of subjects that do respond to treatment with erenumab and subjects who do not respond to treatment with erenumab using Magnetic Resonance Imaging (MRI).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: June 30, 2022
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria

• 18-65 years of age

• Episodic migraine (with or without aura) or chronic migraine according to the diagnostic criteria included within the International Classification of Headache Disorders 3 (ICHD-3)

• 6-25 migraine days per month on average over the 3 months prior to screening, confirmed by run-in phase prospective data collection

• Duration since migraine onset of at least 12 months prior to screening based on medical records and/or patient self-report

Exclusion Criteria

• Older than 50 years of age at migraine onset

• History of cluster headache or hemiplegic migraine

• Continuous headache pain (i.e. no pain-free periods of any duration during the one month before screening)

• Opioid- or butalbital-containing analgesics on 6 or more days per month during the 2 months prior to the start of the baseline phase

• History of major psychiatric disorder such as schizophrenia and bipolar disorder

• History or evidence of any unstable or clinically significant medical condition, that in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion

• No therapeutic response in migraine prevention after an adequate therapeutic trial of 4 or more of the following medication categories: Category 1- divalproex sodium, sodium valproate; Category 2- topiramate; Category 3- beta-blockers; Category 4- tricyclic antidepressants; Category 5- venlafaxine or desvenlafaxine, duloxetine or milnacipran; Category 6- flunarizine, verapamil; Category 7- lisinopril, candesartan; Category 8- botulinum toxin. No therapeutic response is defined as no reduction in headache frequency, duration, or severity after administration of the medication for at least 6 weeks at the generally accepted therapeutic dose(s) based on the investigator's assessment. Lack of sustained response to a medication and failure to tolerate a therapeutic dose are not considered to be "no therapeutic response".

• Concomitant use of 3 or more of the following medications for migraine prevention within 2 months before the start of the baseline phase or throughout the study: divalproex sodium, sodium valproate, topiramate, carbamazepine, gabapentin, beta-blockers, tricyclic antidepressants, venlafaxine, desvenlafaxine, duloxetine, milnacipran, flunarizine, verapamil, lomerizine, lisinopril, candesartan, clonidine, guanfacine, cyproheptadine, methysergide, pizotifen, butterbur, feverfew, magnesium (at least 600 mg per day), riboflavin (at least 100 mg per day). Use of up to two medications is permitted as long as the dose has been stable for at least 2 months before the start of the run-in phase and during the study.

• Botulinum toxin (in the head and/or neck region) within 4 months before the start of the baseline phase and throughout the study

• Ergotamine derivatives, steroids, and triptans used for migraine prophylaxis within 2 months before the start of the baseline phase and throughout the study

• Procedures (e.g. nerve blocks) used for migraine prophylaxis within 2 months before the start of the baseline phase and throughout the study

• History of myocardial infarction, stroke, transient ischemic attack, unstable angina, coronary artery bypass surgery, or other revascularization procedures within 12 months prior to screening.

• Contraindications to MRI including, but not limited to: Metal implants, aneurysm clips, severe claustrophobia, implanted electronic devices, insulin or infusion pump, cochlear/otologic/ear implant, non-removable prosthesis, implanted shunts/catheters, certain intrauterine devices, tattooed makeup, body piercings that cannot be removed, metal fragments, wire sutures or metal staples.

• Factors that Reduce MR Image Quality and Interpretability: dental braces or other non-removable devices (e.g. retainers); prior brain surgery; known brain MRI abnormality that in the investigator's opinion will significantly impact MRI data

• Sensory disorders that in the investigator's opinion might affect perception of cutaneous thermal stimuli (e.g. peripheral neuropathy)

• Pregnancy

• Lactation

• Not willing to use a reliable form of contraception (for women of childbearing potential) through 16 weeks after the last dose of erenumab. Acceptable methods of birth control include not having intercourse, hormonal birth control methods, intrauterine devices, surgical contraceptive methods, or two barrier methods (each partner must use a barrier method) with spermicide. A reliable form of contraception must be started prior to or at the time of starting the run-in phase. Not being of childbearing potential is defined as any woman who: 1) is post-menopausal by history, defined as: a) At least 55 years of age with cessation of menses for 12 or more months, OR b) Younger than 55 years of age but no spontaneous menses for at least 2 years, OR c)Younger than 55 years of age and spontaneous menses within the past 1 year, but currently amenorrheic (e.g. spontaneous or secondary to hysterectomy), AND with postmenopausal gonadotropin levels (luteinizing hormone and follicle-stimulating hormone levels at least 40 IU/L) or postmenopausal estradiol level (less than 5 ng/dL) or according to the definition of "postmenopausal range" for the laboratory involved, OR d) Underwent bilateral oophorectomy, OR e) Underwent hysterectomy, OR f) Underwent bilateral salpingectomy

• Currently receiving treatment in another drug study or an investigational device study, or less than 90 days prior to screening since ending treatment on another investigational device or drug study(-ies)

• Has received calcitonin gene-related peptide (CGRP) monoclonal antibody within 4 months of the start of the run-in phase

• Active chronic pain condition that in the investigator's opinion is unrelated to migraine (e.g. chronic pelvic pain)

• Acute pain condition that in the investigator's opinion is unrelated to migraine (e.g. post-surgical pain)

• Unable to provide informed consent

• Less than 80% compliance with providing headache diary data during the run-in phase (i.e. provides data on less than 80% of days)

Related Conditions & MeSH terms

• Migraine
• Migraine Disorders

Intervention

Drug:
• Erenumab
Erenumab will be used per label instructions.

Locations

Country	Name	City	State
United States	Mayo Clinic in Arizona	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Resting State Functional Connectivity	Brain MRI resting state functional connectivity measured as global efficiency percentage. An increase in global efficiency suggests an improvement in the ability of the brain regions to functionally communicate on a global scale. Efficiency relates to the network. In this case, the investigators defined the network to be the pain matrix. Increased efficiency would mean the connectivity within the matrix is increased and more efficient. This has not been attributed to a clinical outcome but is rather a characteristic of the network.	8 weeks
Secondary	Erenumab Responders	The number of participants who responded to erenumab treatment. Treatment response was defined as at least a 50% reduction in the frequency of migraine days during weeks 5-8 compared to the 4 week pre-treatment run-in phases as recorded in the headache diary.	8 weeks
Secondary	Iron Accumulation in Periaqueductal Gray Brain Region	Iron accumulation in the periaqueductal gray as measured by magnetic resonance imaging (MRI) transverse relaxation rates (T2*).	8 weeks
Secondary	Iron Accumulation in Anterior Cingulate Cortex Brain Region	Iron accumulation in the anterior cingulate cortex as measured by magnetic resonance imaging (MRI) transverse relaxation rates (T2*).	8 weeks
Secondary	Change in the Migraine Disability Assessment Questionnaire (MIDAS)	The MIDAS questionnaire consists of 5 questions that assess the degree of headache related disability. Each question asks the patient to record the number of days in the past 3 months where a headache has impacted various daily life activities. The individual responses to each of the five questions are then added to obtain a total score and level of disability. A total score of 0-5 days reflects little or no disability (Grade I); 6-10 days is mild disability (Grade II); 11-20 days is moderate disability (Grade III) and over 21 days is severe disability (Grade IV). A lower score indicates less disability while a higher score reflects more disability.	Baseline, 8 weeks
Secondary	ROI-ROI Functional Connectivity of Middle Temporal Left With Supramarginal Gyrus Right Regions of the Brain	Temporal correlations in blood oxygen level dependent (BOLD) signal fluctuations between selected regions of interest (ROIs). The correlation coefficient ( r ) is measured between seed regions. This measurement is bound by the range [ -1 to 1]. In order to perform statistical tests (such as T-tests) we Fisher transform the correlation coefficient from [-1 1] to a real number [ -infinity infinity] Mathematically it is: z=atanh( r ). The Z-score themselves are functional connectivity between the regions and do not serve as clinical biomarkers. The difference, and longitudinal changes are of greater interest as they indicate alterations to normal pain processing. A more efficient pain processing network would suggest that more of these regions are being enlisted and with greater connectivity.	8 weeks
Secondary	ROI-ROI Functional Connectivity of Temporal Pole Right With Middle Occipital Right	Temporal correlations in blood oxygen level dependent (BOLD) signal fluctuations between selected regions of interest (ROIs). The correlation coefficient ( r ) is measured between seed regions. This measurement is bound by the range [ -1 to 1]. In order to perform statistical tests (such as T-tests) we Fisher transform the correlation coefficient from [-1 1] to a real number [ -infinity infinity] Mathematically it is: z=atanh( r ). The Z-score themselves are functional connectivity between the regions and do not serve as clinical biomarkers. The difference, and longitudinal changes are of greater interest as they indicate alterations to normal pain processing. A more efficient pain processing network would suggest that more of these regions are being enlisted and with greater connectivity.	8 weeks
Secondary	ROI-ROI Functional Connectivity of Inferior Lateral Parietal Right With Middle Frontal Left	Temporal correlations in blood oxygen level dependent (BOLD) signal fluctuations between selected regions of interest (ROIs). The correlation coefficient ( r ) is measured between seed regions. This measurement is bound by the range [ -1 to 1]. In order to perform statistical tests (such as T-tests) we Fisher transform the correlation coefficient from [-1 1] to a real number [ -infinity infinity] Mathematically it is: z=atanh( r ). The Z-score themselves are functional connectivity between the regions and do not serve as clinical biomarkers. The difference, and longitudinal changes are of greater interest as they indicate alterations to normal pain processing. A more efficient pain processing network would suggest that more of these regions are being enlisted and with greater connectivity.	8 weeks
Secondary	ROI-ROI Functional Connectivity of Dorsolateral Prefrontal Cortex Left With Hypothalamus Right	Temporal correlations in blood oxygen level dependent (BOLD) signal fluctuations between selected regions of interest (ROIs). The correlation coefficient ( r ) is measured between seed regions. This measurement is bound by the range [ -1 to 1]. In order to perform statistical tests (such as T-tests) we Fisher transform the correlation coefficient from [-1 1] to a real number [ -infinity infinity] Mathematically it is: z=atanh( r ). The Z-score themselves are functional connectivity between the regions and do not serve as clinical biomarkers. The difference, and longitudinal changes are of greater interest as they indicate alterations to normal pain processing. A more efficient pain processing network would suggest that more of these regions are being enlisted and with greater connectivity.	8 weeks
Secondary	ROI-ROI Functional Connectivity of Inferior Lateral Parietal Right With Supramarginal Gyrus Right	Temporal correlations in blood oxygen level dependent (BOLD) signal fluctuations between selected regions of interest (ROIs). The correlation coefficient ( r ) is measured between seed regions. This measurement is bound by the range [ -1 to 1]. In order to perform statistical tests (such as T-tests) we Fisher transform the correlation coefficient from [-1 1] to a real number [ -infinity infinity] Mathematically it is: z=atanh( r ). The Z-score themselves are functional connectivity between the regions and do not serve as clinical biomarkers. The difference, and longitudinal changes are of greater interest as they indicate alterations to normal pain processing. A more efficient pain processing network would suggest that more of these regions are being enlisted and with greater connectivity.	8 weeks
Secondary	ROI-ROI Functional Connectivity of Ventromedial Prefrontal Cortex Left With Pulvinar Right	Temporal correlations in blood oxygen level dependent (BOLD) signal fluctuations between selected regions of interest (ROIs). The correlation coefficient ( r ) is measured between seed regions. This measurement is bound by the range [ -1 to 1]. In order to perform statistical tests (such as T-tests) we Fisher transform the correlation coefficient from [-1 1] to a real number [ -infinity infinity] Mathematically it is: z=atanh( r ). The Z-score themselves are functional connectivity between the regions and do not serve as clinical biomarkers. The difference, and longitudinal changes are of greater interest as they indicate alterations to normal pain processing. A more efficient pain processing network would suggest that more of these regions are being enlisted and with greater connectivity.	8 weeks

External Links

•   Mayo Clinic Clinical Trials