Physiopathology, Diagnosis and Therapy of Primary Cephalalgia and Adaptive Disorders
5 janvier 2021 mis à jour par: IRCCS National Neurological Institute "C. Mondino" Foundation
Biomarker Identification to Predict the Evolution of Migraine From an Episodic to a Chronic Condition
The main aim of the present pilot study is to prove the possibility to use the Nitroglycerin (NTG) model to describe the pathophysiology of headache using task-free advanced Magnetic Resonance Imaging (MRI) techniques, in order to depict the static changes of the ictal and inter-ictal phase of migraine attacks vs the pain free state in healthy subjects and to compare that with the spontaneous headache attack experienced by chronic migraineurs.
Aperçu de l'étude
Statut
Complété
Les conditions
Description détaillée
Resting state functional magnetic resonance imaging (rs-fMRI) has depicted cyclical functional connectivity changes during the ictal and inter-ictal phase of the migraine attack. In this pilot study, Functional Connectivity (FC) changes during nitroglycerin (NTG) induced migraine attacks were assessed vs the pain-free condition in healthy subjects.
To this end, subjects with episodic migraine (EM) without aura were enrolled. NTG-triggered a spontaneous-like migraine attack in the subjects. They underwent 4 rs-fMRI scan repetitions during different phases of the attack (baseline, prodromal, full blown, recovery phase) with a 3 Tesla MR scanner. According to the pain field literature, several regions of interests were studied, in particular the thalamic areas and the salience network (SN) were selected as primary areas of interest for the analyses. Subjects' rs-fMRI data were first processed with a seed-based correlation analysis (SCA) to assess the static changes in FC between the thalamus and the rest of the brain during the experiment. The wavelet coherence approach (WCA) were also applied to test the changes in time-in-phase coherence between the thalamus and the salience network (SN).
Healthy subject were administered nitroglycerin as well and scanned at a pain free baseline and after 3 hours in order to compare the response.
The rebound headache that followed acute drug withdrawal were used as a surrogate paradigm of spontaneous attack. Patients with chronic migraine and medication overuse were hospitalized for a supervised withdrawal program at the Mondino Foundation; during the program if they experienced a rebound headache attack, they were scanned with a rs-fMRI acquisition.
The acquired imagines were analyzed with the same procedure regarding the evaluation of static and dynamic functional connectivity fluctuation.
Type d'étude
Observationnel
Inscription (Réel)
15
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Pavia, Italie, 27100
- Headache Science Center
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans à 60 ans (Adulte)
Accepte les volontaires sains
Oui
Sexes éligibles pour l'étude
Tout
Méthode d'échantillonnage
Échantillon non probabiliste
Population étudiée
Subjects with episodic migraine without aura; patients with chronic migraine and medication overuse; healthy subjects
La description
Episodic migraineurs
Inclusion Criteria:
- age between 18-60 years;
- diagnosis of episodic migraine without aura developed before the age of 50;
- no current prophylactic treatment for migraine prevention;
- chronic migraineurs with medication overuse according to the ICHDIII criteria
Exclusion Criteria:
- chronic or medication-overuse headache or cluster headache diagnosis;
- any chronic pain condition or disorders other than migraine;
- an alleged diagnosis of major psychiatric disorders such as depression, bipolar affective disorder and schizophrenia;
- a diagnosis of tension type headache with a frequency of more than 5 days per month;
- any cardiovascular diseases in which the NTG use could be contraindicated;
- blood pressure hypotension, closed angle glaucoma, anaemia;
- women in child bearing, breast feeding; continuous use of benzodiazepines;
- any neuroradiological pathological findings at a previous MRI scan of the head.
Chronic migraineurs
Inclusion Criteria:
- age between 18-60 years;
- diagnosis of migraine without aura developed before the age of 50 according to the ICHD III criteria;
- currently chronic migraineurs with medication overuse according to The International Classification of Headache Disorders 3rd edition (ICHDIII) criteria.
Exclusion Criteria:
- any chronic pain condition or disorders other than migraine;
- an alleged diagnosis of major psychiatric disorders such as depression, bipolar affective disorder and schizophrenia;
- a diagnosis of tension type headache with a frequency of more than 5 days per month;
- any cardiovascular diseases in which the NTG use could be contraindicated;
- blood pressure hypotension, closed angle glaucoma, anaemia; women in child bearing, breast feeding;
- continuous use of benzodiazepines;
- any neuroradiological pathological findings at a previous MRI scan of the head.
Healthy subjects
Inclusion Criteria:
- age between 18-60 years;
- overall good clinical condition, no neurological findings at the physical examination.
Exclusion criteria:
- history of episodic or chronic or medication-overuse headache or cluster headache diagnosis according to the International Chronic Headache Disease (ICHD) III criteria;
- any chronic pain condition or disorders other than migraine;
- an alleged diagnosis of major psychiatric disorders such as depression, bipolar affective disorder and schizophrenia;
- a diagnosis of tension type headache with a frequency of more than 5 days per month;
- any cardiovascular diseases in which the NTG use could be contraindicated;
- blood pressure hypotension, closed angle glaucoma, anaemia;
- women in child bearing, breast feeding;
- continuous use of benzodiazepines;
- any neuroradiological pathological findings at the baseline MRI scan of the head.
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
Cohortes et interventions
Groupe / Cohorte |
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Chronic migraineurs
This group includes patients with chronic migraine.
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Control group
This group includes healthy subjects.
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Episodic migraineurs
This group includes patients with episodic migraine
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Functional Connectivity (FC) changes
Délai: Up to 6 hours
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Functional connectivity pattern of changes profiling the different condition of the migraine experience.
To depict the static and dynamics changes of brain activity during a migraine attack; ii) To validate the use of the NTG-induced attacks paradigm as a reliable instrument combined with an fMRI approach to compare the induced vs the spontaneous attack; iii) To describe possible differences in brain activity between attacks in chronic and episodic migraineurs.
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Up to 6 hours
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Magnetic Resonance Imaging (MRI)
Délai: Up to 6 hours
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To acquire sufficient MRI to identify feature patterns that can profile patient's condition using machine learning (ML) and deep learning (DL) algorithms.
This can be achieved by combining clinical, psychological, biological, neurophysiological and MRI-derived features into a multimodal multi-parametric approach suitable for patient's classification.
The ML and DL approaches could also be adopted to predict chronification, as well as the response to a withdrawal program for medication overuse headache.
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Up to 6 hours
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Monthly migraine frequency (day/month)
Délai: Up to 6 hours
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To acquire clinical data to identify feature patterns that can profile patient's condition using machine learning (ML) and deep learning (DL) algorithms.
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Up to 6 hours
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Disease duration (years)
Délai: Up to 6 hours
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To acquire clinical data to identify feature patterns that can profile patient's condition using machine learning (ML) and deep learning (DL) algorithms.
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Up to 6 hours
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Nausea (number)
Délai: Up to 6 hours
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As a feature of the migraine attack.To acquire clinical data to identify feature patterns that can profile patient's condition using machine learning (ML) and deep learning (DL) algorithms.
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Up to 6 hours
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Vomiting (number)
Délai: Up to 6 hours
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As a feature of the migraine attack.To acquire clinical data to identify feature patterns that can profile patient's condition using machine learning (ML) and deep learning (DL) algorithms.
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Up to 6 hours
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Photophobia (number)
Délai: Up to 6 hours
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As a feature of the migraine attack.To acquire clinical data to identify feature patterns that can profile patient's condition using machine learning (ML) and deep learning (DL) algorithms.
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Up to 6 hours
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Phonophobia (number)
Délai: Up to 6 hours
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To acquire clinical data to identify feature patterns that can profile patient's condition using machine learning (ML) and deep learning (DL) algorithms.
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Up to 6 hours
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Aggravation by movement (number)
Délai: Up to 6 hours
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As a feature of the migraine attack.
To acquire clinical data to identify feature patterns that can profile patient's condition using machine learning (ML) and deep learning (DL) algorithms.
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Up to 6 hours
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Throbbing pain (number)
Délai: Up to 6 hours
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As a feature of the migraine attack.
To acquire clinical data to identify feature patterns that can profile patient's condition using machine learning (ML) and deep learning (DL) algorithms.
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Up to 6 hours
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Abortive medication (number of intake/month)
Délai: Up to 6 hours
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To acquire clinical data to identify feature patterns that can profile patient's condition using machine learning (ML) and deep learning (DL) algorithms.
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Up to 6 hours
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Publications générales
- Schulte LH, May A. Functional Neuroimaging in Migraine: Chances and Challenges. Headache. 2016 Oct;56(9):1474-1481. doi: 10.1111/head.12944. Epub 2016 Sep 22.
- Karsan N, Bose PR, O'Daly O, Zelaya FO, Goadsby PJ. Alterations in Functional Connectivity During Different Phases of the Triggered Migraine Attack. Headache. 2020 Jul;60(7):1244-1258. doi: 10.1111/head.13865. Epub 2020 Jun 22.
- Thomsen LL, Kruuse C, Iversen HK, Olesen J. A nitric oxide donor (nitroglycerin) triggers genuine migraine attacks. Eur J Neurol. 1994 Sep;1(1):73-80. doi: 10.1111/j.1468-1331.1994.tb00053.x.
- Amin FM, Hougaard A, Magon S, Sprenger T, Wolfram F, Rostrup E, Ashina M. Altered thalamic connectivity during spontaneous attacks of migraine without aura: A resting-state fMRI study. Cephalalgia. 2018 Jun;38(7):1237-1244. doi: 10.1177/0333102417729113. Epub 2017 Aug 30.
- Maniyar FH, Sprenger T, Monteith T, Schankin C, Goadsby PJ. Brain activations in the premonitory phase of nitroglycerin-triggered migraine attacks. Brain. 2014 Jan;137(Pt 1):232-41. doi: 10.1093/brain/awt320. Epub 2013 Nov 25.
- Sances G, Tassorelli C, Pucci E, Ghiotto N, Sandrini G, Nappi G. Reliability of the nitroglycerin provocative test in the diagnosis of neurovascular headaches. Cephalalgia. 2004 Feb;24(2):110-9. doi: 10.1111/j.1468-2982.2004.00639.x.
- Tassorelli C, Joseph SA, Buzzi MG, Nappi G. The effects on the central nervous system of nitroglycerin--putative mechanisms and mediators. Prog Neurobiol. 1999 Apr;57(6):607-24. doi: 10.1016/s0301-0082(98)00071-9.
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude (Réel)
31 août 2018
Achèvement primaire (Réel)
31 mars 2019
Achèvement de l'étude (Réel)
15 décembre 2020
Dates d'inscription aux études
Première soumission
21 décembre 2020
Première soumission répondant aux critères de contrôle qualité
5 janvier 2021
Première publication (Réel)
6 janvier 2021
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
6 janvier 2021
Dernière mise à jour soumise répondant aux critères de contrôle qualité
5 janvier 2021
Dernière vérification
1 novembre 2020
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- IMAGO2020
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Non
Étudie un produit d'appareil réglementé par la FDA américaine
Non
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