Migraine DisordersPhase 4RESET BRAINNCT03977649
A Functional MRI Study on Erenumab Treatment Effects in Episodic Migraine Patients
A Phase 4 study testing erenumab in people with Migraine Disorders, run by Novartis Pharmaceuticals at 5 sites in Italy.
Trial summary
The purpose of this study is to investigate the effects of erenumab on central sensitization and brain networks connectivity of migraine patients Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Migraine Disorders
- What is being tested?
- erenumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 5 sitesItaly
- Study dates
- 30 Jul 2019to 5 Jul 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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
- 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
Who cannot join
- 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:
Show all 15Show fewer
- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Italy5 sites
Novartis Investigative Site
L’Aquila
Novartis Investigative Site
Milan, MI, 20132
Novartis Investigative Site
Milan, MI, 20133
Novartis Investigative Site
Naples, 80138
Novartis Investigative Site
Pavia, PV, 27100
About this study
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
The purpose of this study is to investigate the effects of erenumab on central sensitization and brain networks connectivity of migraine patients
Read the 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
- Conditions
- Migraine Disorders
- Being tested
- erenumab, placebo
- Keywords
- AMG334, erenumab, functional MRI, connectivity
- 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
erenumab 140 mg sc every 4 weeks
placeboDrug
placebo sc every 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| erenumab | Experimental | monthly subcutaneous erenumab 140 mg for 12 weeks Receives: Drug: erenumab |
| placebo | Placebo comparator | monthly subcutaneous masked placebo for 12 weeks. Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: baseline, month 3, month 6
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
Measured: baseline, month 3, month 6
Secondary outcomes (5)
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
Measured: month 3, month 6
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
Measured: baseline, month 3, month 6
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
Measured: month 3, month 6
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
Measured: baseline, month 3, month 6
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
Measured: baseline, month 3, month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2019
- Study start30 Jul 2019
- Primary completion5 Jul 2021
- Study completion5 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Migraine DisordersStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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
- Randomised
- Intervention model
- Crossover
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03977649
- Sponsor's protocol ID
- CAMG334AIT03
- Acronym
- RESET BRAIN
- Status last verified
- Aug 2021
- First submitted
- 4 Jun 2019
- Last updated
- 13 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03977649
- Acronym / sponsor ID
- RESET BRAIN / CAMG334AIT03
- Conditions
- Migraine Disorders
- Keywords
- AMG334, erenumab, functional MRI, connectivity
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 30 Jul 2019 (actual)
- Primary completion
- 5 Jul 2021 (actual)
- Study completion
- 5 Jul 2021 (actual)
- First posted
- 6 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| erenumab | Experimental | Drug: erenumabmonthly subcutaneous erenumab 140 mg for 12 weeks |
| placebo | Placebo comparator | Drug: placebomonthly subcutaneous masked placebo for 12 weeks. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (15 listed)
- 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.
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 |
|---|---|---|
| erenumaberenumab 140 mg sc every 4 weeks | Drug | erenumab |
| placeboplacebo sc every 4 weeks | Drug | placebo |
Primary outcome
z-score maps change difference between-treatment-groups
Time frame: baseline, month 3, month 6
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.
Time frame: baseline, month 3, month 6
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
5 secondary outcomes
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
Time frame: month 3, month 6
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
Time frame: baseline, month 3, month 6
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
Time frame: month 3, month 6
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
Time frame: baseline, month 3, month 6
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
Time frame: baseline, month 3, month 6
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2021.
- Individual participant dataSharing planned: Yes. 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
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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.
The record lists no contact. Use the official record to reach the sponsor.
5 sites 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 Disorders, run by Novartis Pharmaceuticals at 5 sites in Italy.
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 3 inclusion and 15 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 13 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Italy. 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. Some participants in this study may receive a placebo. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
z-score maps change difference between-treatment-groups (time frame: baseline, month 3, month 6). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Aug 2021.