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Cluster HeadacheNCT06206772

Resting State Functional Connectivity in Cluster Headache

An observational study of Cluster Headache and Headache Disorders, run by IRCCS National Neurological Institute "C. Mondino" Foundation at 1 site in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Cluster headache is a highly disabling primary headache disorder, characterized by severe, excruciating, recurrent unilateral headache attacks. Typically, attacks' onset displays a circadian rhythm, and bout recurrence happens in a circannual fashion. Read more about this study

Who is it for?
Ages 18 to 70 yearsHealthy volunteers can take part
Conditions the study is for
Cluster Headache, Headache Disorders
What is being tested?
Resting state HD-EEG recording
How many people
20 participants
Where
1 siteItaly
Study dates
1 Nov 2021to Feb 2025
Phase
Observational
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 70 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Study population: Subjects with episodic and chronic cluster headache patients attending the outpatient clinic of the Headache Science \& Neurorehabilitation Center of the IRCCS Mondino Foundation (Pavia, Italy).

Who may be able to join

  • Diagnosis of 3.1.1 episodic cluster headache, or 3.1.2 chronic cluster headache, according to the International Classification of Headache Disorders-3 (ICHD-3) criteria
  • History of at least 1 year of disease
  • For the active-phase recording (T0) in eCH, no preventive medication ongoing or verapamil at a stable dose for at least 2 weeks
  • For the remission-phase recording (T1), no preventive medication ongoing, and at least 14 headache-free days since preventive discontinuation
  • Age and sex-matched healthy volunteers, without history of headache disorders except sporadic tension-type headache according to ICHD-3 criteria

Who cannot join

  • 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
Show all 21Show fewer
  • 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 psychoactive substances possibly interfering with EEG recording (eg benzodiazepines)
  • Other conditions possibly influencing EEG recording
  • Brain anomalies detected on MRI
  • Healthy controls (HCs)
  • 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
  • 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 psychoactive substances possibly interfering with EEG recording (eg benzodiazepines)
  • Other conditions possibly influencing EEG recording

Trial locations and contacts

1 site in 1 country.

Italy1 site, 1 recruiting
  • Headache Science & Neurorehabilitation Center

    Pavia, 27100

    Roberto De Icco, Prof, 00382380425, roberto.deicco@mondino.it

    Recruiting

Other trials in Italy

About this study

Official title: The Role of Resting State Networks Connectivity in Cluster Headache: a HD-EEG Study

Cluster headache is a highly disabling primary headache disorder, characterized by severe, excruciating, recurrent unilateral headache attacks. Typically, attacks' onset displays a circadian rhythm, and bout recurrence happens in a circannual fashion. Notably, the mechanisms underlying the shift between the remission phase and cluster bout are poorly understood.

Thus, the investigators aim to study brain connectivity in episodic cluster headache patients. Additionally, an explorative analysis of functional connectivity in chronic cluster headache patients will be performed.

Read the detailed description

Electroencephalogram (EEG) is widely available as a powerful mean to non-invasively study brain connectivity. High density EEG (HD-EEG), enables to record electrical brain activity with high temporal and 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, thus detecting potential markers or predictors for therapeutic interventions.

Previous neurophysiological studies focused on EEG and to assess functional connectivity or spectral analysis in migraine patients, with no data in cluster headache. Conventional studies found higher slow wave activity (predominantly theta) in the inter-ictal 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.

The primary aim of the study is to evaluate changes in functional connectivity in episodic cluster headache patients, comparing the active phase with the remission phase. Additionally, an explorative analysis of functional connectivity in chronic cluster headache patients will be performed.

Study design:

Episodic cluster headache patients (eCH) will be evaluated in two separate timepoints: during the active phase (T0), defined as at least one week of active bout, and in remission phase (T1), defined as at leat 14 days without headache and without any ongoing preventive medication. During each visit, clinical data will be collected, and an HD-EEG will be performed.

Chronic cluster headache patients (cCH) will be evaluated in a single timepoint, and healthy controls will undergo HD-EEG registration once.

HD-EEG registration:

Participants will perform 4 recordings (6 minutes each) in resting-state condition, 2 with opened eyes, and 2 with closed eyes, in a randomized order.

The investigators will analyze the resting state FC 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, a tailored analysis pipe-line that was previously developed and validated to reconstruct neural sources from cortical/subcortical gray matter will be performed. 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 there are no previous studies on HD-EEG functional connectivity in cluster headache, our sample size analysis was based on the work of Bjork (Bjork et al., 2009). A difference between groups in the theta relative power band equal to 0.04 (±0.04) will be considered as clinically meaningful. Considering a two-tailed t-test for the comparison with confidence interval 95%; power: 80%, the minimum suggested sample size was 20 subjects for 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.

Being tested
Resting state HD-EEG recording
Medical subject headings
Cluster Headache, Headache Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Resting state HD-EEG recordingDiagnostic test

    All subjects will be recorded with a resting state HD-EEG recording. 12 minutes in the eyes closed and 12 minutes in the eyes open condition.

Study groups in NCT06206772
Study groupRoleWhat they receive
Healthy subjectsNot described
Receives: Diagnostic Test: Resting state HD-EEG recording
Episodic cluster headache, activeNot described
Receives: Diagnostic Test: Resting state HD-EEG recording
Episodic cluster headache, remissionNot described
Receives: Diagnostic Test: Resting state HD-EEG recording
Chronic cluster headacheNot described
Receives: Diagnostic Test: Resting state HD-EEG recording

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Difference in absolute functional connectivity values (continuous variable, without unit of measurement) in resting state networks (RSN-FC) in episodic cluster headache patients between active and remission phases

    To compare HD-EEG functional connectivity in episodic cluster headache patients between the two phases of the disease

    Measured: Through study completion, an average of 2 years

  2. Differences in absolute functional connectivity values (continuous variable, without unit of measurement) in resting state networks (RSN-FC) between episodic cluster headache patients and healthy controls

    To compare HD-EEG functional connectivity between episodic cluster headache patients in the two phases of the disease and healthy controls

    Measured: Through study completion, an average of 2 years

Secondary outcomes (2)
  1. Differences in absolute functional connectivity values (continuous variable, without unit of measurement) in resting state networks (RSN-FC) between episodic cluster headache patients and chronic cluster headache patients

    To compare HD-EEG functional connectivity between episodic cluster headache patients and chronic cluster headache patients

    Measured: Through study completion, an average of 1 year

  2. Differences in absolute functional connectivity values (continuous variable, without unit of measurement) in resting state networks (RSN-FC) between chronic cluster headache patients and healthy controls

    To compare HD-EEG functional connectivity between chronic cluster headache patients and healthy controls

    Measured: Single evaluation in chronic cluster headache (cCH) vs. healthy controls (HCs)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jan 2024
  2. Study start1 Nov 2021
  3. Primary completionDec 2024 (estimated)
  4. Study completionFeb 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case-control
Time perspective
Cross-sectional
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06206772
Sponsor's protocol ID
HD-EEG in Cluster Headache
Status last verified
Jan 2024
First submitted
15 Dec 2023
Last updated
16 Jan 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 29368949
  • 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.

    PubMed 19705061
  • 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.

    PubMed 31035929
  • 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.

    PubMed 28963615
  • 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.

    PubMed 27807767
  • 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.

    PubMed 34258580
  • 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.

    PubMed 33200500
  • 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.

    PubMed 25713521

Questions about this trial

What is this clinical trial studying?

An observational study of Cluster Headache and Headache Disorders, run by IRCCS National Neurological Institute "C. Mondino" Foundation at 1 site 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 5 inclusion and 21 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: status not confirmed, as of the sponsor's last update on 16 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Cinzia Fattore, MD (0382380385 ext. 0039, cinzia.fattore@mondino.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Difference in absolute functional connectivity values (continuous variable, without unit of measurement) in resting state networks (RSN-FC) in episodic cluster headache patients between active and remission phases (time frame: Through study completion, an average of 2 years). 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?

On the ClinicalTrials.gov record for NCT06206772, which also lists 8 linked publications.

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 16 Jan 2024.

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