Trial Outcomes & Findings for Imaging the Migraine Brain Pre- and Post-Erenumab (NCT NCT03773562)

NCT ID: NCT03773562

Last Updated: 2024-01-09

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 50 participants
• Primary outcome timeframe: 8 weeks
• Results posted on: 2024-01-09

Participant Flow

Participant milestones

Measure	Erenumab All participants receive erenumab 140mg by subcutaneous injection at baseline and again 4 weeks later. Erenumab: Erenumab will be used per label instructions.
Overall Study STARTED	50
Overall Study COMPLETED	29
Overall Study NOT COMPLETED	21

Reasons for withdrawal

Measure	Erenumab All participants receive erenumab 140mg by subcutaneous injection at baseline and again 4 weeks later. Erenumab: Erenumab will be used per label instructions.
Overall Study Did not have 6-25 migraine days during run-in	10
Overall Study Lost to Follow-up	10
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Imaging the Migraine Brain Pre- and Post-Erenumab

Baseline characteristics by cohort

Measure	Erenumab n=50 Participants All participants receive erenumab 140mg by subcutaneous injection at baseline and again 4 weeks later. Erenumab: Erenumab will be used per label instructions.
Age, Continuous	40.3 years STANDARD_DEVIATION 13 • n=5 Participants
Sex: Female, Male Female	46 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	43 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	41 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	7 Participants n=5 Participants
Region of Enrollment United States	50 participants n=5 Participants

PRIMARY outcome

Timeframe: 8 weeks

Population: Of the 32 participants to complete a functional MRI (fMRI) of the brain, 18 participants were identified as erenumab responders and 14 were erenumab non-responders.

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.

Outcome measures

Measure	Erenumab n=32 Participants All participants receive erenumab 140mg by subcutaneous injection at baseline and again 4 weeks later. Erenumab: Erenumab will be used per label instructions.
Resting State Functional Connectivity Erenamab responders	26.2 global efficiency percentage Standard Error 1.1
Resting State Functional Connectivity Erenumab non-responders	23.3 global efficiency percentage Standard Error 0.7

SECONDARY outcome

Timeframe: 8 weeks

Population: Of the 50 participants enrolled, 32 received erenumab treatment and completed a functional MRI (fMRI) of the brain.

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.

Outcome measures

Measure	Erenumab n=32 Participants All participants receive erenumab 140mg by subcutaneous injection at baseline and again 4 weeks later. Erenumab: Erenumab will be used per label instructions.
Erenumab Responders	18 Participants

SECONDARY outcome

Timeframe: 8 weeks

Population: Of the 28 participants with complete MRI T2\* results, 15 participants were identified as erenumab responders and 13 were erenumab non-responders.

Iron accumulation in the periaqueductal gray as measured by magnetic resonance imaging (MRI) transverse relaxation rates (T2*).

Outcome measures

Measure	Erenumab n=28 Participants All participants receive erenumab 140mg by subcutaneous injection at baseline and again 4 weeks later. Erenumab: Erenumab will be used per label instructions.
Iron Accumulation in Periaqueductal Gray Brain Region Erenumab responders	43.0 milliseconds (ms) Standard Error 1
Iron Accumulation in Periaqueductal Gray Brain Region Erenumab non-responders	32.5 milliseconds (ms) Standard Error 1

SECONDARY outcome

Timeframe: 8 weeks

Population: Of the 28 participants with complete MRI T2\* results, 15 participants were identified as erenumab responders and 13 were erenumab non-responders.

Iron accumulation in the anterior cingulate cortex as measured by magnetic resonance imaging (MRI) transverse relaxation rates (T2*).

Outcome measures

Measure	Erenumab n=28 Participants All participants receive erenumab 140mg by subcutaneous injection at baseline and again 4 weeks later. Erenumab: Erenumab will be used per label instructions.
Iron Accumulation in Anterior Cingulate Cortex Brain Region Erenumab responders	50 milliseconds (ms) Standard Error 1
Iron Accumulation in Anterior Cingulate Cortex Brain Region Erenumab non-responders	40 milliseconds (ms) Standard Error 1

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: Of the 28 participants that completed the MIDAS questionnaire, 15 participants were identified as erenumab responders and 13 were erenumab non-responders.

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.

Outcome measures

Measure	Erenumab n=28 Participants All participants receive erenumab 140mg by subcutaneous injection at baseline and again 4 weeks later. Erenumab: Erenumab will be used per label instructions.
Change in the Migraine Disability Assessment Questionnaire (MIDAS) Erenumab responders	-16.5 score on a scale Standard Error 16
Change in the Migraine Disability Assessment Questionnaire (MIDAS) Erenumab non-responders	5.8 score on a scale Standard Error 13

SECONDARY outcome

Timeframe: 8 weeks

Population: Of the 32 participants to complete a functional MRI (fMRI) of the brain, 18 participants were identified as erenumab responders and 14 were erenumab non-responders.

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.

Outcome measures

Measure	Erenumab n=32 Participants All participants receive erenumab 140mg by subcutaneous injection at baseline and again 4 weeks later. Erenumab: Erenumab will be used per label instructions.
ROI-ROI Functional Connectivity of Middle Temporal Left With Supramarginal Gyrus Right Regions of the Brain Erenumab responder	0.34 correlation coefficient
ROI-ROI Functional Connectivity of Middle Temporal Left With Supramarginal Gyrus Right Regions of the Brain Erenumab non-responder	0.02 correlation coefficient

SECONDARY outcome

Timeframe: 8 weeks

Population: Of the 32 participants to complete a functional MRI (fMRI) of the brain, 18 participants were identified as erenumab responders and 14 were erenumab non-responders.

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.

Outcome measures

Measure	Erenumab n=32 Participants All participants receive erenumab 140mg by subcutaneous injection at baseline and again 4 weeks later. Erenumab: Erenumab will be used per label instructions.
ROI-ROI Functional Connectivity of Temporal Pole Right With Middle Occipital Right Erenumab responders	0.24 correlation coefficient
ROI-ROI Functional Connectivity of Temporal Pole Right With Middle Occipital Right Erenumab non-responders	-0.08 correlation coefficient

SECONDARY outcome

Timeframe: 8 weeks

Population: Of the 32 participants to complete a functional MRI (fMRI) of the brain, 18 participants were identified as erenumab responders and 14 were erenumab non-responders.

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.

Outcome measures

Measure	Erenumab n=32 Participants All participants receive erenumab 140mg by subcutaneous injection at baseline and again 4 weeks later. Erenumab: Erenumab will be used per label instructions.
ROI-ROI Functional Connectivity of Inferior Lateral Parietal Right With Middle Frontal Left Erenumab responders	-0.07 correlation coefficient
ROI-ROI Functional Connectivity of Inferior Lateral Parietal Right With Middle Frontal Left Erenumab non-responders	0.24 correlation coefficient

SECONDARY outcome

Timeframe: 8 weeks

Population: Of the 32 participants to complete a functional MRI (fMRI) of the brain, 18 participants were identified as erenumab responders and 14 were erenumab non-responders.

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.

Outcome measures

Measure	Erenumab n=32 Participants All participants receive erenumab 140mg by subcutaneous injection at baseline and again 4 weeks later. Erenumab: Erenumab will be used per label instructions.
ROI-ROI Functional Connectivity of Dorsolateral Prefrontal Cortex Left With Hypothalamus Right Erenumab responder	0.02 correlation coefficient
ROI-ROI Functional Connectivity of Dorsolateral Prefrontal Cortex Left With Hypothalamus Right Erenumab non-responder	-0.18 correlation coefficient

SECONDARY outcome

Timeframe: 8 weeks

Population: Of the 32 participants to complete a functional MRI (fMRI) of the brain, 18 participants were identified as erenumab responders and 14 were erenumab non-responders.

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.

Outcome measures

Measure	Erenumab n=32 Participants All participants receive erenumab 140mg by subcutaneous injection at baseline and again 4 weeks later. Erenumab: Erenumab will be used per label instructions.
ROI-ROI Functional Connectivity of Inferior Lateral Parietal Right With Supramarginal Gyrus Right Erenumab responders	0.68 correlation coefficient
ROI-ROI Functional Connectivity of Inferior Lateral Parietal Right With Supramarginal Gyrus Right Erenumab non-responders	0.38 correlation coefficient

SECONDARY outcome

Timeframe: 8 weeks

Population: Of the 32 participants to complete a functional MRI (fMRI) of the brain, 18 participants were identified as erenumab responders and 14 were erenumab non-responders.

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.

Outcome measures

Measure	Erenumab n=32 Participants All participants receive erenumab 140mg by subcutaneous injection at baseline and again 4 weeks later. Erenumab: Erenumab will be used per label instructions.
ROI-ROI Functional Connectivity of Ventromedial Prefrontal Cortex Left With Pulvinar Right Erenumab responder	0.18 correlation coefficient
ROI-ROI Functional Connectivity of Ventromedial Prefrontal Cortex Left With Pulvinar Right Erenumab non-responder	-0.07 correlation coefficient

Adverse Events

Erenumab

Serious events: 0 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Erenumab n=36 participants at risk All participants receive erenumab 140mg by subcutaneous injection at baseline and again 4 weeks later. Erenumab: Erenumab will be used per label instructions.
General disorders Dizziness	8.3% 3/36 • Number of events 3 • Adverse events were collected on each participant from the time of the first erenumab treatment through the end of the safety follow up visit (8 weeks after the last dose of the investigational product) for a total of approximately 12 weeks. Out of 50 participants, 36 received the first dose of erenumab but 4 withdrew from the study prior to completing a function MRI (fMRI) of the brain.
General disorders Flank pain	2.8% 1/36 • Number of events 1 • Adverse events were collected on each participant from the time of the first erenumab treatment through the end of the safety follow up visit (8 weeks after the last dose of the investigational product) for a total of approximately 12 weeks. Out of 50 participants, 36 received the first dose of erenumab but 4 withdrew from the study prior to completing a function MRI (fMRI) of the brain.
General disorders Loss of balance	2.8% 1/36 • Number of events 1 • Adverse events were collected on each participant from the time of the first erenumab treatment through the end of the safety follow up visit (8 weeks after the last dose of the investigational product) for a total of approximately 12 weeks. Out of 50 participants, 36 received the first dose of erenumab but 4 withdrew from the study prior to completing a function MRI (fMRI) of the brain.
General disorders Weight gain	2.8% 1/36 • Number of events 1 • Adverse events were collected on each participant from the time of the first erenumab treatment through the end of the safety follow up visit (8 weeks after the last dose of the investigational product) for a total of approximately 12 weeks. Out of 50 participants, 36 received the first dose of erenumab but 4 withdrew from the study prior to completing a function MRI (fMRI) of the brain.
General disorders Arm twitching	2.8% 1/36 • Number of events 1 • Adverse events were collected on each participant from the time of the first erenumab treatment through the end of the safety follow up visit (8 weeks after the last dose of the investigational product) for a total of approximately 12 weeks. Out of 50 participants, 36 received the first dose of erenumab but 4 withdrew from the study prior to completing a function MRI (fMRI) of the brain.
Infections and infestations Ear infection	2.8% 1/36 • Number of events 1 • Adverse events were collected on each participant from the time of the first erenumab treatment through the end of the safety follow up visit (8 weeks after the last dose of the investigational product) for a total of approximately 12 weeks. Out of 50 participants, 36 received the first dose of erenumab but 4 withdrew from the study prior to completing a function MRI (fMRI) of the brain.
Infections and infestations Urinary tract infection	2.8% 1/36 • Number of events 1 • Adverse events were collected on each participant from the time of the first erenumab treatment through the end of the safety follow up visit (8 weeks after the last dose of the investigational product) for a total of approximately 12 weeks. Out of 50 participants, 36 received the first dose of erenumab but 4 withdrew from the study prior to completing a function MRI (fMRI) of the brain.
General disorders Agitation	2.8% 1/36 • Number of events 1 • Adverse events were collected on each participant from the time of the first erenumab treatment through the end of the safety follow up visit (8 weeks after the last dose of the investigational product) for a total of approximately 12 weeks. Out of 50 participants, 36 received the first dose of erenumab but 4 withdrew from the study prior to completing a function MRI (fMRI) of the brain.
General disorders Communication issues	2.8% 1/36 • Number of events 1 • Adverse events were collected on each participant from the time of the first erenumab treatment through the end of the safety follow up visit (8 weeks after the last dose of the investigational product) for a total of approximately 12 weeks. Out of 50 participants, 36 received the first dose of erenumab but 4 withdrew from the study prior to completing a function MRI (fMRI) of the brain.
General disorders Insomnia	2.8% 1/36 • Number of events 1 • Adverse events were collected on each participant from the time of the first erenumab treatment through the end of the safety follow up visit (8 weeks after the last dose of the investigational product) for a total of approximately 12 weeks. Out of 50 participants, 36 received the first dose of erenumab but 4 withdrew from the study prior to completing a function MRI (fMRI) of the brain.
Infections and infestations Covid-19 infection	2.8% 1/36 • Number of events 1 • Adverse events were collected on each participant from the time of the first erenumab treatment through the end of the safety follow up visit (8 weeks after the last dose of the investigational product) for a total of approximately 12 weeks. Out of 50 participants, 36 received the first dose of erenumab but 4 withdrew from the study prior to completing a function MRI (fMRI) of the brain.
General disorders Allergic reaction	2.8% 1/36 • Number of events 1 • Adverse events were collected on each participant from the time of the first erenumab treatment through the end of the safety follow up visit (8 weeks after the last dose of the investigational product) for a total of approximately 12 weeks. Out of 50 participants, 36 received the first dose of erenumab but 4 withdrew from the study prior to completing a function MRI (fMRI) of the brain.
General disorders West Nile Virus	2.8% 1/36 • Number of events 1 • Adverse events were collected on each participant from the time of the first erenumab treatment through the end of the safety follow up visit (8 weeks after the last dose of the investigational product) for a total of approximately 12 weeks. Out of 50 participants, 36 received the first dose of erenumab but 4 withdrew from the study prior to completing a function MRI (fMRI) of the brain.
General disorders Itching/skin sensitivity	8.3% 3/36 • Number of events 3 • Adverse events were collected on each participant from the time of the first erenumab treatment through the end of the safety follow up visit (8 weeks after the last dose of the investigational product) for a total of approximately 12 weeks. Out of 50 participants, 36 received the first dose of erenumab but 4 withdrew from the study prior to completing a function MRI (fMRI) of the brain.
General disorders Tinnitus	2.8% 1/36 • Number of events 1 • Adverse events were collected on each participant from the time of the first erenumab treatment through the end of the safety follow up visit (8 weeks after the last dose of the investigational product) for a total of approximately 12 weeks. Out of 50 participants, 36 received the first dose of erenumab but 4 withdrew from the study prior to completing a function MRI (fMRI) of the brain.
General disorders Worsening headache	2.8% 1/36 • Number of events 1 • Adverse events were collected on each participant from the time of the first erenumab treatment through the end of the safety follow up visit (8 weeks after the last dose of the investigational product) for a total of approximately 12 weeks. Out of 50 participants, 36 received the first dose of erenumab but 4 withdrew from the study prior to completing a function MRI (fMRI) of the brain.
General disorders Constipation	38.9% 14/36 • Number of events 14 • Adverse events were collected on each participant from the time of the first erenumab treatment through the end of the safety follow up visit (8 weeks after the last dose of the investigational product) for a total of approximately 12 weeks. Out of 50 participants, 36 received the first dose of erenumab but 4 withdrew from the study prior to completing a function MRI (fMRI) of the brain.
General disorders Abdominal pain	2.8% 1/36 • Number of events 1 • Adverse events were collected on each participant from the time of the first erenumab treatment through the end of the safety follow up visit (8 weeks after the last dose of the investigational product) for a total of approximately 12 weeks. Out of 50 participants, 36 received the first dose of erenumab but 4 withdrew from the study prior to completing a function MRI (fMRI) of the brain.
General disorders Injection site erythema	2.8% 1/36 • Number of events 1 • Adverse events were collected on each participant from the time of the first erenumab treatment through the end of the safety follow up visit (8 weeks after the last dose of the investigational product) for a total of approximately 12 weeks. Out of 50 participants, 36 received the first dose of erenumab but 4 withdrew from the study prior to completing a function MRI (fMRI) of the brain.

Additional Information

Dr. Todd Schwedt

Mayo Clinic

Phone: 480-342-2695

Email: schwedt.todd@mayo.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place