Searching for Novel Biological Phenotypes in Migraine Patients Resistant to Treatments (SPHERA_WP1_2)

August 17, 2024 updated by: IRCCS National Neurological Institute "C. Mondino" Foundation

Unraveling the Spectrum of Migraine Resistant to Treatments: Searching for Novel Biological PHEnotypes and theRApeutic Approaches (SPHERA Project)

The investigators aim to define the neurofunctional phenotype of migraine patients who did not respond to at least 3 preventive treatments, including monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) pathway (NON-responders).

Primary aim will be to assess and compare changes in functional resting-state connectivity at baseline and after three months of mAbs treatment between patients who will achieve a reduction of monthly migraine days >/= than 50% (namely Responders) and those who will not (namely Responders).

The 2 groups will undergo a neurofunctional profile by means of High Density-electroencephalogram (HD-EEG) and functional-magnetic resonance imaging (fMRI).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

High Density-electroencephalogram (HD-EEG) and functional-magnetic resonance imaging (fMRI) are widely available as powerful means to non-invasively study brain connectivity features in migraine patients.

They both enables to record brain activity with high spatial resolution. HD-EEG also contributes to high temporal resolution, while fMRI contributes to precise evaluation of deep cortical and subcortical areas, relevant in migraine pathophysiology.

Aim of the study is to evaluate changes in resting-state functional connectivity in patients undergoing preventive mAbs treatment using HD- EEG and fMRI. These findings will allow the identification of a multibiomarkers panel signature of migraine patients resisting to specifically targeted preventive treatments and potentially unveiling other molecular targets for therapeutic approaches.

STUDY DESIGN:

This study is part of the SPHERA project receiving funding from the Italian Ministry of Health (GR-2021-12372429). Patients will be enrolled from those attending the outpatient clinic of IRCCS Mondino Institute (Pavia) and Neurology Department of the University of L'Aquila (Avezzano).

The investigators will collect clinical data and perform neurofunctional profiling of migraine patients at baseline (T0) and after three months of mAbs treatment (T3).

METHODS:

All patients will undergo a resting-state functional evaluation through high density-EEG and subset of 40 patients will also be studied in parallel with fMRI at baseline.

- HD-EEG: the investigators will randomly acquire 4 recordings (6 minutes each) in resting-state condition, 2 with opened eyes, and 2 with closed eyes. The investigators will consider the following frequency bands: delta (1-4 Hz), theta (4-8 Hz), alfa (8-13 Hz), beta (13-30 Hz), gamma (30-80 Hz).

Acquisition parameters will be: High-Pass: 0.5 Hz; Low-Pass: 100 Hz; Notch: 50 Hz. For analysis of HD-EEG data, the investigators will use a tailored analysis pipe-line that was previously developed and validated to reconstruct neural sources from cortical/subcortical gray matter (Semprini, 2021). EEG signals will be band-pass filtered (1-80 Hz) and down-sampled at 250 Hz. Biological artifacts will be rejected using Independent Component Analysis (ICA). EEG signals will be referenced with a customized version of the Reference Electrode Standardization Technique (REST) (Mantini, 2007). A matrix will estimate the relationship between the measured scalp potentials and the dipoles corresponding to brain sources. Sources reconstruction will be performed with the exact low-resolution brain electromagnetic tomography (eLORETA) algorithm.

- Resting state fMRI: ICA will be applied to resting state-fMRI to characterize the RSNs. For each subject and for each identified RSN, the mean functional connectivity will be calculated. A seed based component analysis will be applied in order to obtain a whole brain map to describe the strength of the connectivity of each voxel of the brain image with the region of interest (seed). The region of interests selection will be based on available literature and previous experience.

Study Type

Observational

Enrollment (Estimated)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Italy
      • Pavia, Italy, 27100
        • Recruiting
        • Headache Science & Neurorehabilitation Unit
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

N/A

Sampling Method

Probability Sample

Study Population

Subjects with chronic and high frequency episodic migraine attending the outpatient clinic of the Headache Science & Neurorehabilitation Unit of the IRCCS Mondino Foundation (Pavia, Italy) and the Neurology Department of the University of L'Aquila (Avezzano, Italy).

Description

Inclusion Criteria:

  • male and female patients aged 18 to 75 years
  • diagnosis of episodic migraine or chronic migraine according to ICHD-3 criteria
  • for episodic migraine: 8-14 monthly migraine days in the previous 3 months
  • diagnosis of resistant migraine, defined by having failed at least 3 classes of migraine preventatives and suffer from at least 8 debilitating monthly headache days for at least 3 consecutive months
  • patients naive to CGRP targeting treatments

Exclusion Criteria:

  • history of major psychiatric or other neurological conditions
  • diagnosis of other primary or secondary headache disorders (only sporadic tension-type headache is allowed if the patients can clearly differentiate between the 2 types of headaches)
  • changes in ongoing preventive treatment (if any) in the previous 3 months
  • clinically significant medical conditions
  • chronic pain conditions
  • alcohol and/or drug abuse
  • pregnancy or lactation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Responders
Patients with high frequency episodic or chronic migraine undergoing treatment with monoclonal antibodies directed against calcitonin gene related peptide pathway (mAbs) who obtained a reduction in monthly migraine days equal or higher than 50% compared to pre-treatment values.
Drug: MAbs
Monthly or quarterly mAbs administration
Other Names:
  • Monoclonal antibody targeting the CGRP pathway (ligand or receptor) (mAbs)
NON-Responders
Patients with high frequency episodic or chronic migraine undergoing mAbs treatment who obtained a reduction in monthly migraine days < 50% compared to pre-treatment values.
Drug: MAbs
Monthly or quarterly mAbs administration
Other Names:
  • Monoclonal antibody targeting the CGRP pathway (ligand or receptor) (mAbs)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
RSN-FC assessed through HD-EEG
Time Frame: Baseline (T0), and three months of mAbs treatment (T1)
Resting state functional connectivity assessed through HD-EEG (continuous variable, without unit of measurement)
Baseline (T0), and three months of mAbs treatment (T1)
RSN-FC assessed through MRI
Time Frame: Baseline (T0)
Resting state functional connectivity assessed through MRI (continuous variable, without unit of measurement)
Baseline (T0)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison between baseline RSN-FC assessed through HD-EEG
Time Frame: Baseline (T0)
Comparison between RSN-FC changes assessed through HD-EEG (continuous variable, without unit of measurement)
Baseline (T0)
Comparison between baseline RSN-FC assessed through MRI
Time Frame: Baseline (T0)
Comparison between RSN-FC changes assessed through MRI (continuous variable, without unit of measurement)
Baseline (T0)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS National Neurological Institute "C. Mondino" Foundation

Collaborators

University of L'Aquila

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 10, 2023

Primary Completion (Estimated)

February 1, 2026

Study Completion (Estimated)

May 1, 2026

Study Registration Dates

First Submitted

August 8, 2024

First Submitted That Met QC Criteria

August 17, 2024

First Posted (Actual)

August 20, 2024

Study Record Updates

Last Update Posted (Actual)

August 20, 2024

Last Update Submitted That Met QC Criteria

August 17, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SPHERA-functional

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Migraine Disorders

Clinical Trials on MAbs

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Poland

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe