MigrainePhase 4NCT03773562
Imaging the Migraine Brain Pre- and Post-Erenumab
A Phase 4 study testing Erenumab in people with Migraine, run by Mayo Clinic at 1 site in United States.
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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Migraine
- What is being tested?
- Erenumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Mar 2019to 30 Jun 2022
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 24Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Imaging the Migraine Brain Pre- and Post-Erenumab: an MRI Study to Identify Functional and Structural Changes That Correlate With Patient Improvement
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).
- Conditions
- Migraine
- Being tested
- Erenumab
- Keywords
- Migraine, Magnetic Resonance Imaging, Brain Structure, Brain Function
- Medical subject headings
- Migraine Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ErenumabDrug
Also called Aimovig
Erenumab will be used per label instructions.
| Study group | Role | What they receive |
|---|---|---|
| Erenumab | Other | All participants receive erenumab 140mg by subcutaneous injection at baseline and again 4 weeks later. Receives: Drug: Erenumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 8 weeks
Secondary outcomes (10)
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.
Measured: 8 weeks
Iron Accumulation in Periaqueductal Gray Brain Region
Iron accumulation in the periaqueductal gray as measured by magnetic resonance imaging (MRI) transverse relaxation rates (T2*).
Measured: 8 weeks
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*).
Measured: 8 weeks
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.
Measured: Baseline, 8 weeks
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.
Measured: 8 weeks
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.
Measured: 8 weeks
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.
Measured: 8 weeks
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.
Measured: 8 weeks
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.
Measured: 8 weeks
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.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2018
- Study start25 Mar 2019
- Primary completion30 Jun 2022
- Study completion30 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MigraineStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Todd J. Schwedt, Mayo Clinic
- Investigators
- Todd J Schwedt, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03773562
- Sponsor's protocol ID
- 18-001497
- Status last verified
- Dec 2023
- First submitted
- 27 Nov 2018
- Last updated
- 9 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Schwedt TJ, Nikolova S, Dumkrieger G, Li J, Wu T, Chong CD. Longitudinal changes in functional connectivity and pain-induced brain activations in patients with migraine: a functional MRI study pre- and post- treatment with Erenumab. J Headache Pain. 2022 Dec 14;23(1):159. doi: 10.1186/s10194-022-01526-5.
PubMed 36517767
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Imaging the Migraine Brain Pre- and Post-Erenumab: an MRI Study to Identify Functional and Structural Changes That Correlate With Patient Improvement
- ClinicalTrials.gov ID
- NCT03773562
- Acronym / sponsor ID
- 18-001497
- Conditions
- Migraine
- Keywords
- Migraine, Magnetic Resonance Imaging, Brain Structure, Brain Function
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- 25 Mar 2019 (actual)
- Primary completion
- 30 Jun 2022 (actual)
- Study completion
- 30 Jun 2022 (actual)
- First posted
- 12 Dec 2018 (actual)
- Results
- Posted 9 Jan 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Erenumab | Other | Drug: ErenumabAll participants receive erenumab 140mg by subcutaneous injection at baseline and again 4 weeks later. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ErenumabAlso: AimovigErenumab will be used per label instructions. | Drug | Erenumab |
Primary outcome
Resting State Functional Connectivity
Time frame: 8 weeks
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.
10 secondary outcomes
Erenumab Responders
Time frame: 8 weeks
Iron Accumulation in Periaqueductal Gray Brain Region
Time frame: 8 weeks
Iron Accumulation in Anterior Cingulate Cortex Brain Region
Time frame: 8 weeks
Change in the Migraine Disability Assessment Questionnaire (MIDAS)
Time frame: Baseline, 8 weeks
ROI-ROI Functional Connectivity of Middle Temporal Left With Supramarginal Gyrus Right Regions of the Brain
Time frame: 8 weeks
ROI-ROI Functional Connectivity of Temporal Pole Right With Middle Occipital Right
Time frame: 8 weeks
ROI-ROI Functional Connectivity of Inferior Lateral Parietal Right With Middle Frontal Left
Time frame: 8 weeks
ROI-ROI Functional Connectivity of Dorsolateral Prefrontal Cortex Left With Hypothalamus Right
Time frame: 8 weeks
ROI-ROI Functional Connectivity of Inferior Lateral Parietal Right With Supramarginal Gyrus Right
Time frame: 8 weeks
ROI-ROI Functional Connectivity of Ventromedial Prefrontal Cortex Left With Pulvinar Right
Time frame: 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36517767Schwedt TJ, Nikolova S, Dumkrieger G, Li J, Wu T, Chong CD. Longitudinal changes in functional connectivity and pain-induced brain activations in patients with migraine: a functional MRI study pre- and post- treatment with Erenumab. J Headache Pain. 2022 Dec 14;23(1):159. doi: 10.1186/s10194-022-01526-5.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Todd J Schwedt principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Erenumab in people with Migraine, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Resting State Functional Connectivity (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03773562, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2024.