MigraineNCT04696510
Physiopathology, Diagnosis and Therapy of Primary Cephalalgia and Adaptive Disorders
An observational study of Migraine, run by IRCCS National Neurological Institute "C. Mondino" Foundation at 1 site in Italy.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Migraine
- How many people
- 15 participants
- Where
- 1 siteItaly
- Study dates
- 31 Aug 2018to 15 Dec 2020
- 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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: Subjects with episodic migraine without aura; patients with chronic migraine and medication overuse; healthy subjects
Who may be able to join
- 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;
Show all 9Show fewer
- 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.
Who cannot join
- 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;
Show all 26Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the detailed description
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
- Migraine
- Keywords
- Episodic migraine, Chronic migraine, Medication overuse, Nitroglycerin, fMRI
- Medical subject headings
- Migraine Disorders, Prescription Drug Overuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Chronic migraineurs | This group includes patients with chronic migraine. | |
| Control group | This group includes healthy subjects. | |
| Episodic migraineurs | This group includes patients with episodic migraine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Functional Connectivity (FC) changes
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.
Measured: Up to 6 hours
Secondary outcomes (10)
Magnetic Resonance Imaging (MRI)
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.
Measured: Up to 6 hours
Monthly migraine frequency (day/month)
To acquire clinical data to identify feature patterns that can profile patient's condition using machine learning (ML) and deep learning (DL) algorithms.
Measured: Up to 6 hours
Disease duration (years)
To acquire clinical data to identify feature patterns that can profile patient's condition using machine learning (ML) and deep learning (DL) algorithms.
Measured: Up to 6 hours
Nausea (number)
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.
Measured: Up to 6 hours
Vomiting (number)
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.
Measured: Up to 6 hours
Photophobia (number)
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.
Measured: Up to 6 hours
Phonophobia (number)
To acquire clinical data to identify feature patterns that can profile patient's condition using machine learning (ML) and deep learning (DL) algorithms.
Measured: Up to 6 hours
Aggravation by movement (number)
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.
Measured: Up to 6 hours
Throbbing pain (number)
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.
Measured: Up to 6 hours
Abortive medication (number of intake/month)
To acquire clinical data to identify feature patterns that can profile patient's condition using machine learning (ML) and deep learning (DL) algorithms.
Measured: Up to 6 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2021
- Study start31 Aug 2018
- Primary completion31 Mar 2019
- Study completion15 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for MigraineStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Prospective
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- IRCCS National Neurological Institute "C. Mondino" Foundation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Cristina Tassorelli, Prof, Principal investigator, IRCCS Mondino Foundation, Pavia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04696510
- Sponsor's protocol ID
- IMAGO2020
- Status last verified
- Nov 2020
- First submitted
- 21 Dec 2020
- Last updated
- 6 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 32568433Thomsen 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.
PubMed 24283432Schulte 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.
PubMed 27654831Amin 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.
PubMed 28853611Maniyar 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.
PubMed 24277718Sances 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.
PubMed 14728706Tassorelli 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.
PubMed 10221784
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biomarker Identification to Predict the Evolution of Migraine From an Episodic to a Chronic Condition
- ClinicalTrials.gov ID
- NCT04696510
- Acronym / sponsor ID
- IMAGO2020
- Conditions
- Migraine
- Keywords
- Episodic migraine, Chronic migraine, Medication overuse, Nitroglycerin, fMRI
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- IRCCS National Neurological Institute "C. Mondino" FoundationUniversity, hospital or other
- Study start
- 31 Aug 2018 (actual)
- Primary completion
- 31 Mar 2019 (actual)
- Study completion
- 15 Dec 2020 (actual)
- First posted
- 6 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Chronic migraineurs | – | –This group includes patients with chronic migraine. |
| Control group | – | –This group includes healthy subjects. |
| Episodic migraineurs | – | –This group includes patients with episodic migraine |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Subjects with episodic migraine without aura; patients with chronic migraine and medication overuse; healthy subjects
Key inclusion criteria (9 listed)
- 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;
Key exclusion criteria (26 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Functional Connectivity (FC) changes
Time frame: Up to 6 hours
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.
10 secondary outcomes
Magnetic Resonance Imaging (MRI)
Time frame: Up to 6 hours
Monthly migraine frequency (day/month)
Time frame: Up to 6 hours
Disease duration (years)
Time frame: Up to 6 hours
Nausea (number)
Time frame: Up to 6 hours
Vomiting (number)
Time frame: Up to 6 hours
Photophobia (number)
Time frame: Up to 6 hours
Phonophobia (number)
Time frame: Up to 6 hours
Aggravation by movement (number)
Time frame: Up to 6 hours
Throbbing pain (number)
Time frame: Up to 6 hours
Abortive medication (number of intake/month)
Time frame: Up to 6 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2021.
- Background: PubMed 32568433Karsan 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.
- Background: PubMed 24283432Thomsen 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.
- Background: PubMed 27654831Schulte 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.
- Background: PubMed 28853611Amin 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.
- Background: PubMed 24277718Maniyar 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.
- Results publication: PubMed 14728706Sances 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.
- Results publication: PubMed 10221784Tassorelli 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cristina Tassorelli, Prof principal investigator
IRCCS Mondino Foundation, Pavia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Migraine, 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 9 inclusion and 26 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: finished, as of the sponsor's last update on 6 Jan 2021. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Functional Connectivity (FC) changes (time frame: Up to 6 hours). 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 NCT04696510, which also lists 7 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 6 Jan 2021.