Back to resultsA Functional MRI Study on Erenumab Treatment Effects in Episodic Migraine Patients (RESET BRAIN)
Primary Purpose
Migraine Disorders
Status
Completed
Phase
Phase 4
Locations
Italy
Study Type
Interventional
Intervention
erenumab
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Migraine Disorders focused on measuring AMG334, erenumab, functional MRI, connectivity
Eligibility Criteria
Inclusion Criteria:
- Signed informed consent must be obtained prior to participation in the study History of migraine with or without aura for at least 12 months prior to screening 4. Migraine frequency: ≥ 4 and < 15 migraine days per month on average across the 3 months prior to screening and confirmed during the baseline phase based on diary calculation
- Headache frequency: <15 headache days per month on average across the 3 months prior to screening and confirmed during the baseline phase based on diary calculation
- Failure to 2 or more previous treatment categories locally indicated for migraine prophylaxis due to either lack of efficacy or poor tolerability
Exclusion Criteria:
- History of cluster headache or hemiplegic migraine headache
- History of chronic pain disorders and neuropathic pain
- History of head trauma or seizure or major psychiatric disorders or suicidal ideation/behavior at any time before screening
- Currently, receiving any other prophylactic treatment for migraine and/or prohibited medications, non-pharmacologic interventions or devices (any substance, non-pharmacologic intervention or device acting at central nervous system), or less than 60 days or 5 half-lives prior to the start of the baseline period, during the baseline period, or treatment period
- Exposure to botulinum toxin in the head and/or neck region within 4 months prior to the start of the baseline period, during the baseline period, or treatment period.
Taken the following for any indication in any month during the 2 months prior to the start of the baseline period:
- Ergotamines or triptans on ≥ 10 days per month, or
- Simple analgesics (non-steroidal anti-inflammatory drugs [NSAIDs], acetaminophen) on ≥ 15 days per month, or
- Opioid- or butalbital-containing analgesics on ≥4 days per month.
- Previous exposure to erenumab or exposure to any other prophylactic CGRP-targeted therapy (prior to and during the study)
- History or evidence of any other 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
- Subject has any clinically significant vital sign, laboratory, or electrocardiogram (ECG) abnormality during screening that, in the opinion of the investigator, could pose a risk to subject safety or interfere with the study evaluation
- Evidence of drug or alcohol abuse or dependence within 12 months prior to screening, based on medical records or patient self-report
- Pregnant or breastfeeding
- All the clinical conditions for which undergoing an MRI scan is contraindicated
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
erenumab
placebo
Arm Description
monthly subcutaneous erenumab 140 mg for 12 weeks
monthly subcutaneous masked placebo for 12 weeks.
Outcomes
Primary Outcome Measures
z-score maps change difference between-treatment-groups
z score maps are measures of resting state functional connectivity strength in the brain areas involved in pain processing
z-score maps difference between clinical response groups within the two treatment groups.
clinical response assessed as reduction by 50% in monthly migraine days ,MMD, in the last month vs baseline.
z score maps relative to resting state functional connectivity strength in the brain areas involved in pain processing
Secondary Outcome Measures
Correlation (by treatment groups and in all patients) between the changes in the resting state functional connectivity strength, measured as z-score maps, and clinical outcomes
clinical outcomes: the percentage of change in monthly migraine, b. the reduction in monthly average severity of migraine pain, c. the percentage of reduction in monthly number of days with use of acute treatments, d. the change in HIT-6 score
Between-treatment-groups difference in change of resting state functional connectivity strength, from baseline to month 3 of treatment, measured as z-score maps. in the brain regions involved in migraine symptoms
migraine symptoms: a. sensory hypersensitivity (allodynia) b. visual or auditory hypersensitivity (photophobia or phonophobia) c. neurovegetative symptoms (nausea) d. altered emotional control of pain
Correlation (by treatment group and in all patients) between of the changes in the resting state functional connectivity strength of the areas involved in migraine symptoms and the reduction of the respective symptoms
the clinical response here is described as reduction of the migraine symptoms: changes in the Allodynia Symptom Checklist 12 (ASC-12) score as measure of allodynia, the percentage changes in number of days with photophobia and phonophobia, and the percentage changes in number of days with nausea, changes in HADS score as measure of anxiety and depressive behaviour
Baseline resting state functional connectivity strength will be evaluated by treatment group and in all patients as potential predictors of treatment clinical response defined by the achievement of at least 50% reduction of monthly migraine days
baseline functional MRI markers predictive of good clinical response to erenumab
Changes in z-score maps from baseline to month 3 of erenumab treatment and from baseline to month 6 with 3 months with erenumab followed by 3 months of placebo
the effects of the erenumab discontinuation on fMRI after 3 months of placebo treatment
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03977649
Brief Title
A Functional MRI Study on Erenumab Treatment Effects in Episodic Migraine Patients
Acronym
RESET BRAIN
Official Title
A RandomizEd, Double-blind, Cross-over Study to Assess Erenumab effecT on BRAIN Networks Function and Structure in Comparison to Placebo in Episodic Migraine Patients
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Completed
Study Start Date
July 30, 2019 (Actual)
Primary Completion Date
July 5, 2021 (Actual)
Study Completion Date
July 5, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to investigate the effects of erenumab on central sensitization and brain networks connectivity of migraine patients
Detailed Description
This is a randomized, double blind, placebo-controlled trial with a 2-sequence, 2-period, 2-treatment crossover design. The study population will consist of adult male and female subjects with a documented history of episodic migraine (4 to 14 baseline migraine days), who have failed at least 2 previous migraine prophylactic treatment for lack of efficacy or tolerability. After a run-in phase of 4 weeks, patients will be randomized, according to a 1:1 ratio, to a 24 weeks of treatment, as follow:
Sequence 1: A/B
Sequence 2: B/A where: A=monthly subcutaneous erenumab 140 mg for 12 weeks; B=monthly subcutaneous masked placebo for 12 weeks
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Migraine Disorders
Keywords
AMG334, erenumab, functional MRI, connectivity
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Model Description
After a run-in phase of 4 weeks, patients will be randomized, according to a 1:1 ratio, to a 24 weeks of treatment, as follow:
Sequence 1: A/B
Sequence 2: B/A where: A=monthly subcutaneous erenumab 140 mg for 12 weeks; B=monthly subcutaneous masked placebo for 12 weeks.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Study treatments will be all identical in packaging, labeling, schedule of administration, appearance, taste and odor
Allocation
Randomized
Enrollment
62 (Actual)
8. Arms, Groups, and Interventions
Arm Title
erenumab
Arm Type
Experimental
Arm Description
monthly subcutaneous erenumab 140 mg for 12 weeks
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
monthly subcutaneous masked placebo for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
erenumab
Intervention Description
erenumab 140 mg sc every 4 weeks
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
placebo sc every 4 weeks
Primary Outcome Measure Information:
Title
z-score maps change difference between-treatment-groups
Description
z score maps are measures of resting state functional connectivity strength in the brain areas involved in pain processing
Time Frame
baseline, month 3, month 6
Title
z-score maps difference between clinical response groups within the two treatment groups.
Description
clinical response assessed as reduction by 50% in monthly migraine days ,MMD, in the last month vs baseline.
z score maps relative to resting state functional connectivity strength in the brain areas involved in pain processing
Time Frame
baseline, month 3, month 6
Secondary Outcome Measure Information:
Title
Correlation (by treatment groups and in all patients) between the changes in the resting state functional connectivity strength, measured as z-score maps, and clinical outcomes
Description
clinical outcomes: the percentage of change in monthly migraine, b. the reduction in monthly average severity of migraine pain, c. the percentage of reduction in monthly number of days with use of acute treatments, d. the change in HIT-6 score
Time Frame
month 3, month 6
Title
Between-treatment-groups difference in change of resting state functional connectivity strength, from baseline to month 3 of treatment, measured as z-score maps. in the brain regions involved in migraine symptoms
Description
migraine symptoms: a. sensory hypersensitivity (allodynia) b. visual or auditory hypersensitivity (photophobia or phonophobia) c. neurovegetative symptoms (nausea) d. altered emotional control of pain
Time Frame
baseline, month 3, month 6
Title
Correlation (by treatment group and in all patients) between of the changes in the resting state functional connectivity strength of the areas involved in migraine symptoms and the reduction of the respective symptoms
Description
the clinical response here is described as reduction of the migraine symptoms: changes in the Allodynia Symptom Checklist 12 (ASC-12) score as measure of allodynia, the percentage changes in number of days with photophobia and phonophobia, and the percentage changes in number of days with nausea, changes in HADS score as measure of anxiety and depressive behaviour
Time Frame
month 3, month 6
Title
Baseline resting state functional connectivity strength will be evaluated by treatment group and in all patients as potential predictors of treatment clinical response defined by the achievement of at least 50% reduction of monthly migraine days
Description
baseline functional MRI markers predictive of good clinical response to erenumab
Time Frame
baseline, month 3, month 6
Title
Changes in z-score maps from baseline to month 3 of erenumab treatment and from baseline to month 6 with 3 months with erenumab followed by 3 months of placebo
Description
the effects of the erenumab discontinuation on fMRI after 3 months of placebo treatment
Time Frame
baseline, month 3, month 6
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed informed consent must be obtained prior to participation in the study History of migraine with or without aura for at least 12 months prior to screening 4. Migraine frequency: ≥ 4 and < 15 migraine days per month on average across the 3 months prior to screening and confirmed during the baseline phase based on diary calculation
Headache frequency: <15 headache days per month on average across the 3 months prior to screening and confirmed during the baseline phase based on diary calculation
Failure to 2 or more previous treatment categories locally indicated for migraine prophylaxis due to either lack of efficacy or poor tolerability
Exclusion Criteria:
History of cluster headache or hemiplegic migraine headache
History of chronic pain disorders and neuropathic pain
History of head trauma or seizure or major psychiatric disorders or suicidal ideation/behavior at any time before screening
Currently, receiving any other prophylactic treatment for migraine and/or prohibited medications, non-pharmacologic interventions or devices (any substance, non-pharmacologic intervention or device acting at central nervous system), or less than 60 days or 5 half-lives prior to the start of the baseline period, during the baseline period, or treatment period
Exposure to botulinum toxin in the head and/or neck region within 4 months prior to the start of the baseline period, during the baseline period, or treatment period.
Taken the following for any indication in any month during the 2 months prior to the start of the baseline period:
Ergotamines or triptans on ≥ 10 days per month, or
Simple analgesics (non-steroidal anti-inflammatory drugs [NSAIDs], acetaminophen) on ≥ 15 days per month, or
Opioid- or butalbital-containing analgesics on ≥4 days per month.
Previous exposure to erenumab or exposure to any other prophylactic CGRP-targeted therapy (prior to and during the study)
History or evidence of any other 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
Subject has any clinically significant vital sign, laboratory, or electrocardiogram (ECG) abnormality during screening that, in the opinion of the investigator, could pose a risk to subject safety or interfere with the study evaluation
Evidence of drug or alcohol abuse or dependence within 12 months prior to screening, based on medical records or patient self-report
Pregnant or breastfeeding
All the clinical conditions for which undergoing an MRI scan is contraindicated
Facility Information:
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20132
Country
Italy
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20133
Country
Italy
Facility Name
Novartis Investigative Site
City
Pavia
State/Province
PV
ZIP/Postal Code
27100
Country
Italy
Facility Name
Novartis Investigative Site
City
L Aquila
Country
Italy
Facility Name
Novartis Investigative Site
City
Napoli
ZIP/Postal Code
80138
Country
Italy
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
IPD Sharing URL
https://www.clinicalstudydatarequest.com
Learn more about this trial
A Functional MRI Study on Erenumab Treatment Effects in Episodic Migraine Patients
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