Physiopathology, Diagnosis and Therapy of Primary Cephalalgia and Adaptive Disorders

NCT ID: NCT04696510

Last Updated: 2021-01-06

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

COMPLETED

Total Enrollment

15 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-08-31

Study Completion Date

2020-12-15

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Migraine

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Chronic migraineurs

This group includes patients with chronic migraine.

No interventions assigned to this group

Control group

This group includes healthy subjects.

No interventions assigned to this group

Episodic migraineurs

This group includes patients with episodic migraine

No interventions assigned to this group

Eligibility Criteria

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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


* 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.


* age between 18-60 years;
* overall good clinical condition, no neurological findings at the physical examination.

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


* 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


* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 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

Principal Investigators

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Cristina Tassorelli, Prof

Role: PRINCIPAL_INVESTIGATOR

IRCCS Mondino Foundation, Pavia

Locations

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Headache Science Center

Pavia, , Italy

Site Status

Countries

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Italy

References

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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.

Reference Type BACKGROUND
PMID: 32568433 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24283432 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27654831 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28853611 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24277718 (View on PubMed)

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.

Reference Type RESULT
PMID: 14728706 (View on PubMed)

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.

Reference Type RESULT
PMID: 10221784 (View on PubMed)

Other Identifiers

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IMAGO2020

Identifier Type: -

Identifier Source: org_study_id

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