HD-EEG Connectivity Changes in Migraine Patients Undergoing Treatment With Anti-CGRP mAbs

NCT ID: NCT06155123

Last Updated: 2024-01-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

60 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-01-14

Study Completion Date

2024-06-30

Brief Summary

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Migraine is a leading cause of disability with an estimated prevalence of 12% in Europe. The headache field witnessed a breakthrough since the introduction of specific preventive therapies which proved effective and well tolerated, namely the monoclonal antibodies directed against the Calcitonin Gene Related Peptide (CGRP) pathway (mAbs). Their mechanism of action is still debated. Several Authors claimed that, despite the site of action is peripheral (namely outside of the blood brain barrier), the resulting action may take place at central level. Another valuable hypothesis is that the clinical modifications resulting from mAbs treatment may induce functional modulation of several brain areas.

With these premises, the primary aim of the study is to evaluate changes in functional connectivity in patients undergoing preventive mAbs treatment using high density EEG.

Detailed Description

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Electroencephalogram (EEG) is widely available as a powerful mean to non-invasively study brain connectivity features in migraine patients. High density EEG, by means of a minimum of 64 up to 256 electrodes, enables to record electrical brain activity with high spatial resolution. Through the analysis of brain oscillations across different frequency bands (from alpha to delta), it can evaluate sensory, pain processing and information integration, contributing to a better definition of baseline features and to detect potential markers or predictors for therapeutic interventions in an era addressed to precision medicine.

Previous neurophysiological studies focused on EEG and to assess functional connectivity or spectral analysis in migraine patients. Conventional studies found higher slow wave activity (predominantly theta) in the interictal phase and higher excitability in the visual cortex during visual aura.

In 2016 a resting state study showed a predominance of low frequency bands in the ictal phase. The interictal and ictal phases patients also presented a diffuse lower coherence, suggesting low functional connectivity. Furthermore, an altered spatial connectivity for lower alpha-band activities was found in the interictal phases during sensory stimulation by means of HD-EEG, suggesting a thalamocortical dysrhythmia.

Nowadays, targeted preventive migraine therapies are available, namely monoclonal antibodies directed against the Calcitonin Gene Related Peptide (CGRP) pathway (mAbs). They demonstrated high efficacy and tolerability in both chronic and episodic migraine. Despite their peripheral site of action (outside of the blood brain barrier), the resulting action may take place at central level or determine clinical modifications leading to a functional modulation of several brain areas.

The primary aim of the study is to evaluate changes in functional connectivity in patients undergoing preventive mAbs treatment using HD- EEG and eventual connectivity differences between Responders and Non-Responders.

Study design:

Patients will undergo visits planned at baseline (T0) and quarterly (T3-T6) during which clinical data is collected and an HD-EEG is performed. Healthy controls will undergo EEG registration once.

HD-EEG registration:

The investigators will randomly acquire 4 recordings (6 minutes each) in resting-state condition, 2 with opened eyes, and 2 with closed eyes.

Resting state FC will be analyzed among six resting state networks (Default mode network, Dorsal attention network, Ventral attention network, Language network , Somatomotor network and Visual network) in the following frequency bands: alfa 8-12 Hz, beta 13-30 Hz, gamma 31-80 Hz, theta 4-7 Hz. delta 1-3 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. 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). 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

Statistical plan:

The sample size was computed with the freeware online platform www.openepi.com. As few studies focused on functional connectivity evaluation in migraine, with no studies analyzing longitudinal changes during a specific treatment, the sample size analysis was based on the work of Bjork. The investigators thus considered as clinically meaningful a difference between groups in the theta relative power band equal to 0.04 (±0.04). Considering a two-tailed t-test for the comparison with confidence interval 95%; power: 80%, the minimum suggested sample size was 20 subjects for CM group and 20 subjects for HFEM group.

A preliminary normality analysis will be performed to decide whether to use parametric or non-parametric methods, through Shapiro Wilk test.

Numerical variables will be described as mean and standard deviation (or median and quartiles if appropriate), categorical variables as raw numbers and percentages.

Functional connectivity analyses will be conducted for separate bands and eyes closed registration.

Conditions

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Migraine Disorders Chronic Migraine Episodic Migraine

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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HFEM or CM treated with mAbs

Patients with high frequency episodic or chronic migraine undergoing treatment with monoclonal antibodies directed against calcitonin gene related peptide pathway

Monoclonal antibody targeting the CGRP pathway (ligand or receptor) (mAbs)

Intervention Type DRUG

Monthly or quarterly mAbs administration for a year

Healthy Controls

Group of healthy controls comparable for demographic features

No interventions assigned to this group

Interventions

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Monoclonal antibody targeting the CGRP pathway (ligand or receptor) (mAbs)

Monthly or quarterly mAbs administration for a year

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Episodic or chronic migraine diagnosis according to ICHD-3 criteria
* Indication to BoNT-A or mAbs treatment according to AIFA criteria
* Brain MRI performed within 24 months from enrolment

Exclusion Criteria

* Previous or actual history of epilepsy
* Diagnosis of dementia o mental retardation
* Diagnosis of psychiatric illness according to Diagnostic and Statistical Manual of Mental Disorders V
* Other concomitant type of headache (except for sporadic tension type headache)
* Chronic pain conditions
* Pregnancy or breastfeeding
* Concomitant use of electrical stimulators, pace-makers, metallic clips or other metallic foreign bodies
* Previous head surgery
* Ongoing neuroactive prevention therapies or other drugs, or psicoactive substances possibly interfering with EEG recording (eg benzodiazepines)
* Other conditions possibly influencing EEG recording
* Brain anomalies detected on MRI
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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IRCCS National Neurological Institute "C. Mondino" Foundation

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Headache Science & Neurorehabilitation Center

Pavia, , Italy

Site Status RECRUITING

Countries

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Italy

Facility Contacts

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Roberto De Icco, MD

Role: primary

0382380387

References

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Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018 Jan;38(1):1-211. doi: 10.1177/0333102417738202. No abstract available.

Reference Type BACKGROUND
PMID: 29368949 (View on PubMed)

Bjork MH, Stovner LJ, Engstrom M, Stjern M, Hagen K, Sand T. Interictal quantitative EEG in migraine: a blinded controlled study. J Headache Pain. 2009 Oct;10(5):331-9. doi: 10.1007/s10194-009-0140-4. Epub 2009 Aug 25.

Reference Type BACKGROUND
PMID: 19705061 (View on PubMed)

Coppola G, Di Lorenzo C, Parisi V, Lisicki M, Serrao M, Pierelli F. Clinical neurophysiology of migraine with aura. J Headache Pain. 2019 Apr 29;20(1):42. doi: 10.1186/s10194-019-0997-9.

Reference Type BACKGROUND
PMID: 31035929 (View on PubMed)

de Tommaso M, Trotta G, Vecchio E, Ricci K, Siugzdaite R, Stramaglia S. Brain networking analysis in migraine with and without aura. J Headache Pain. 2017 Sep 29;18(1):98. doi: 10.1186/s10194-017-0803-5.

Reference Type BACKGROUND
PMID: 28963615 (View on PubMed)

Cao Z, Lin CT, Chuang CH, Lai KL, Yang AC, Fuh JL, Wang SJ. Resting-state EEG power and coherence vary between migraine phases. J Headache Pain. 2016 Dec;17(1):102. doi: 10.1186/s10194-016-0697-7. Epub 2016 Nov 2.

Reference Type BACKGROUND
PMID: 27807767 (View on PubMed)

Chamanzar A, Haigh SM, Grover P, Behrmann M. Abnormalities in cortical pattern of coherence in migraine detected using ultra high-density EEG. Brain Commun. 2021 Apr 2;3(2):fcab061. doi: 10.1093/braincomms/fcab061. eCollection 2021.

Reference Type BACKGROUND
PMID: 34258580 (View on PubMed)

Semprini M, Bonassi G, Barban F, Pelosin E, Iandolo R, Chiappalone M, Mantini D, Avanzino L. Modulation of neural oscillations during working memory update, maintenance, and readout: An hdEEG study. Hum Brain Mapp. 2021 Mar;42(4):1153-1166. doi: 10.1002/hbm.25283. Epub 2020 Nov 17.

Reference Type BACKGROUND
PMID: 33200500 (View on PubMed)

Aoki Y, Ishii R, Pascual-Marqui RD, Canuet L, Ikeda S, Hata M, Imajo K, Matsuzaki H, Musha T, Asada T, Iwase M, Takeda M. Detection of EEG-resting state independent networks by eLORETA-ICA method. Front Hum Neurosci. 2015 Feb 10;9:31. doi: 10.3389/fnhum.2015.00031. eCollection 2015.

Reference Type BACKGROUND
PMID: 25713521 (View on PubMed)

Other Identifiers

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HD-EEG in mAbs

Identifier Type: -

Identifier Source: org_study_id

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