Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Imaging the Migraine Brain Pre- and Post-Erenumab

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03773562
Recruitment Status : Recruiting
First Posted : December 12, 2018
Last Update Posted : September 18, 2020
Sponsor:
Information provided by (Responsible Party):
Todd J. Schwedt, Mayo Clinic

Tracking Information
First Submitted Date  ICMJE November 27, 2018
First Posted Date  ICMJE December 12, 2018
Last Update Posted Date September 18, 2020
Actual Study Start Date  ICMJE March 25, 2019
Estimated Primary Completion Date July 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 10, 2018)
  • 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
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 10, 2018)
  • 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.
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Imaging the Migraine Brain Pre- and Post-Erenumab
Official Title  ICMJE Imaging the Migraine Brain Pre- and Post-Erenumab: an MRI Study to Identify Functional and Structural Changes That Correlate With Patient Improvement
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: N/A
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
Condition  ICMJE Migraine
Intervention  ICMJE Drug: Erenumab
Erenumab will be used per label instructions.
Other Name: Aimovig
Study Arms  ICMJE Erenumab
All participants receive erenumab 140mg by subcutaneous injection at baseline and again 4 weeks later.
Intervention: Drug: Erenumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 10, 2018)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 1, 2021
Estimated Primary Completion Date July 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03773562
Other Study ID Numbers  ICMJE 18-001497
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Todd J. Schwedt, Mayo Clinic
Study Sponsor  ICMJE Mayo Clinic
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Todd J Schwedt Mayo Clinic
PRS Account Mayo Clinic
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP