Clinical trial NCT03773562: Imaging the Migraine Brain Pre- and Post-Erenumab
Official title: Imaging the Migraine Brain Pre- and Post-Erenumab: an MRI Study to Identify Functional and Structural Changes That Correlate With Patient Improvement
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Migraine
Keywords: Migraine
Magnetic Resonance Imaging
Brain Structure
Brain Function
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2018-12-12
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: 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)

Primary outcomes:
measure: Resting State Functional Connectivity
timeFrame: 8 weeks
Secondary outcomes:
measure: Erenumab Responders
timeFrame: 8 weeks
measure: Iron Accumulation in Periaqueductal Gray Brain Region
timeFrame: 8 weeks
measure: Iron Accumulation in Anterior Cingulate Cortex Brain Region
timeFrame: 8 weeks
measure: Change in the Migraine Disability Assessment Questionnaire (MIDAS)
timeFrame: Baseline, 8 weeks
measure: ROI-ROI Functional Connectivity of Middle Temporal Left With Supramarginal Gyrus Right Regions of the Brain
timeFrame: 8 weeks
measure: ROI-ROI Functional Connectivity of Temporal Pole Right With Middle Occipital Right
timeFrame: 8 weeks
measure: ROI-ROI Functional Connectivity of Inferior Lateral Parietal Right With Middle Frontal Left
timeFrame: 8 weeks
measure: ROI-ROI Functional Connectivity of Dorsolateral Prefrontal Cortex Left With Hypothalamus Right
timeFrame: 8 weeks
measure: ROI-ROI Functional Connectivity of Inferior Lateral Parietal Right With Supramarginal Gyrus Right
timeFrame: 8 weeks
measure: ROI-ROI Functional Connectivity of Ventromedial Prefrontal Cortex Left With Pulvinar Right
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
Study officials:
affiliation: Mayo Clinic
name: Todd J Schwedt
role: PRINCIPAL_INVESTIGATOR
References: