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Imaging the Migraine Brain Pre- and Post-Erenumab

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ClinicalTrials.gov Identifier: NCT03773562
Recruitment Status : Not yet recruiting
First Posted : December 12, 2018
Last Update Posted : December 12, 2018
Sponsor:
Information provided by (Responsible Party):
Todd J. Schwedt, Mayo Clinic

Brief Summary:

The aims of this study are to:

  1. Identify changes in brain function and structure that correlate with response to erenumab.
  2. Develop models using imaging data +/- clinical data to predict which patients will respond to erenumab. Pre-treatment and early post-treatment imaging data will be used separately for predictive modeling.

Condition or disease Intervention/treatment Phase
Migraine Drug: Erenumab Phase 4

Detailed Description:
The study will include 50 participants with migraine aged 18-65 years who have 10-25 migraine days per month at baseline. Following a 4-week headache diary run-in phase, participants will receive two treatments with once monthly subcutaneous injections of erenumab 140 mg. Questionnaires, structured interviews, cognitive tests, quantitative sensory testing and brain imaging will be performed prior to and following erenumab treatment. These data will be collected at early time points after the first treatment as well as at eight weeks following the first treatment to allow for identification of early and late effects of erenumab on clinical, physiologic, and imaging outcomes and to determine if early physiologic and imaging outcomes predict clinical outcomes at eight weeks. Physiologic and imaging data will be compared to already collected data from healthy controls so as to interpret changes that are seen following treatment with erenumab.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Intervention Model Description: All consented and qualifying subjects will receive erenumab treatment. Questionnaires, cognitive testing, and brain MRIs will be completed pre- and post-treatment.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Imaging the Migraine Brain Pre- and Post-Erenumab: an MRI Study to Identify Functional and Structural Changes That Correlate With Patient Improvement
Estimated Study Start Date : January 1, 2019
Estimated Primary Completion Date : September 3, 2020
Estimated Study Completion Date : December 2, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Erenumab
All participants receive erenumab 140mg by subcutaneous injection at baseline and again 4 weeks later.
Drug: Erenumab
Erenumab will be used per label instructions.
Other Name: Aimovig




Primary Outcome Measures :
  1. Changes in Pain-Induced Brain Activations [ Time Frame: Baseline, 8 weeks ]
    Changes in pain-induced regional brain activations (BOLD response) from baseline (pre-treatment) to 8 weeks post-treatment

  2. Changes in Brain Functional Connectivity (temporal correlations in BOLD signal fluctuations) [ Time Frame: Baseline, 8 weeks ]
    Changes in brain functional connectivity (temporal correlations in BOLD signal fluctuations) amongst a priori selected regions of interest from baseline (pre-treatment) to 8 weeks post-treatment


Secondary Outcome Measures :
  1. Accuracy of Predicting Treatment Response [ Time Frame: Baseline, 2 weeks, 5-8 weeks ]
    Multivariate machine‐learning modeling of brain structural and functional data +/- clinical data collected at baseline and at 2 weeks will be utilized for predicting treatment responses measured between 5 and 8 weeks post-treatment.

  2. Early Changes in Pain-Induced Brain Activations [ Time Frame: Baseline, 2 weeks ]
    Changes in pain-induced regional brain activations (BOLD response) from baseline (pre-treatment) to 2 weeks post-treatment

  3. Early Changes in Brain Functional Connectivity (temporal correlations in BOLD signal fluctuations) [ Time Frame: Baseline, 2 weeks ]
    Changes in brain functional connectivity (temporal correlations in BOLD signal fluctuations) amongst a priori selected regions of interest from baseline (pre-treatment) to 2 weeks post-treatment

  4. Changes in Brain Perfusion [ Time Frame: Baseline, 2 weeks, 8 weeks ]
    Changes in arterial spin labeling measures of cerebral blood flow from baseline (pre-treatment) to 2 weeks and 8 weeks post-treatment

  5. Changes in Brain Regional Volumes [ Time Frame: Baseline, 8 weeks ]
    Changes in regional volumes of a priori selected regions of interest from baseline (pre-treatment) to 8 weeks post-treatment

  6. Changes in Brain Cortical Thickness [ Time Frame: Baseline, 8 weeks ]
    Changes in the cortical thickness of a priori selected regions of interest from baseline (pre-treatment) to 8 weeks post-treatment

  7. Changes in Brain White Matter Tract Integrity [ Time Frame: Baseline, 8 weeks ]
    Changes in the integrity of a priori selected white matter tracts measured via diffusion tensor imaging



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
  • 10-25 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 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03773562


Locations
United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Todd J Schwedt Mayo Clinic

Responsible Party: Todd J. Schwedt, Principal Investigator, Mayo Clinic
ClinicalTrials.gov Identifier: NCT03773562     History of Changes
Other Study ID Numbers: 18-001497
First Posted: December 12, 2018    Key Record Dates
Last Update Posted: December 12, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Todd J. Schwedt, Mayo Clinic:
Migraine
Magnetic Resonance Imaging
Brain Structure
Brain Function

Additional relevant MeSH terms:
Migraine Disorders
Headache Disorders, Primary
Headache Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases