MigraineNCT05907655
Study of the Glymphatic System in Migraine
An observational study of Migraine, run by IRCCS San Raffaele at 1 site in Italy.
Trial summary
This study aimed to investigate the role of the glymphatic system in the initiation of migraine attacks, using non-invasive magnetic resonance imaging techniques and a validated model of migraine induction by nitroglycerin administration. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Migraine
- What is being tested?
- Nitroglycerin 0.3 MG, MRI and Blood sampling
- Type of treatment
- Medical device
- How many people
- 50 participants
- Where
- 1 siteItaly
- Study dates
- 30 Apr 2023to 4 Apr 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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: Patients with a diagnosis of episodic migraine without aura, by the standard ICHD diagnostic criteria, will be prospectively recruited. Patients will be allowed to take only one migraine preventive treatment at a stable dose during the study. Healthy controls suffering from any headaches with the exception of infrequent tension-type headache will be excluded from the study.
Who may be able to join
- For patients:
- Diagnosis of migraine, by the ICHD-3 criteria;
- For both patients and healthy controls:
- Age between 18 and 60 years;
- Willing and able to comply with scheduled visits.
Who cannot join
- For patients:
- Overuse of acute medications for headache;
- Continuous or daily headache;
- Other primary headache disorders, with the exception of infrequent tension-type headache.
- For healthy controls:
- Any subject with frequent tension type headache, migraine, cluster headache, other pain syndromes or neurological conditions.
Show all 24Show fewer
- For both patients and healthy controls:
- Allergy to nitroglycerin;
- Major psychiatric disorders such as bipolar affective disorder and schizophrenia;
- Cardiovascular diseases that contraindicated the use of nitroglycerin;
- Intracranial hypertension;
- Cerebral haemorrhage;
- Cerebral trauma;
- Pulmonary toxic oedema;
- Closed angle glaucoma;
- Anaemia;
- Pregnancy and breastfeeding;
- Aortic stenosis or significant hypotension (SBP<90mmHg or <100mmHg and symptomatic) precluding nitroglycerin administration;
- Use of sildenafil;
- Any person unable to lie still within the environment of the MRI scanner for the required period to perform the study;
- Any person where MRI scanning is contraindicated (metal implants, pacemaker, claustrophobia, etc.);
- Use of illicit drugs;
- MRI head showing any brain pathology, such as space-occupying lesions;
- Any person unable to understand and follow the instructions of the investigators.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
IRCCS San Raffaele Hospital
Milan, Milan, 20132
Roberta Messina, MD, PhD
About this study
Official title: Discovering the Functional Role of the Glymphatic System in the Genesis of the Migraine Attack
This study aimed to investigate the role of the glymphatic system in the initiation of migraine attacks, using non-invasive magnetic resonance imaging techniques and a validated model of migraine induction by nitroglycerin administration. Secondarily, the relationship between the function of the glymphatic system during nitroglycerin-induced migraine attacks and sleep architecture and plasma levels of migraine-involved neuropeptides will be investigated.
- Conditions
- Migraine
- Being tested
- Nitroglycerin 0.3 MG, MRI, Blood sampling, Sleep profiler
- Keywords
- migraine, MRI, glymphatic system, sleep, neuropeptides
- Medical subject headings
- Migraine Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitroglycerin 0.3 MGDrug
Sublingual nitroglycerin will be used to provoke spontaneous-like migraine attacks in migraine patients. A dose of 0.9 mg of sublingual nitroglycerin will be used. The same dose will be administrated to controls.
MRIDiagnostic test
The following brain MRI sequences will be acquired before and after nitroglycerin administration: fluid attenuated inversion recovery (FLAIR), 3D T1-weighted inversion recovery prepared gradient echo, diffusion weighted sequence and 3D susceptibility weighted images.
Blood samplingDiagnostic test
Plasma levels of neuropeptides involed in migraine will be measured using commercially available enzyme-linked immune-sorbent assay (ELISA) kits. All ELISA will be performed by the same experienced technician who will be blinded for the clinical diagnosis.
Sleep profilerDevice
Sleep architecture will be investigated using the Sleep Profiler. Sleep Profiler is medical device with CE mark which is produced by Advanced Brain Monitoring and distributed throughout Italy exclusively by Medigas. Sleep staging will be automatically performed for 30-second epochs throughout a dedicated software and a standardized and validated procedure. Frontopolar EEG signal waveforms will be visually inspected to confirm the accuracy of the auto-staging.
| Study group | Role | What they receive |
|---|---|---|
| Adult patients with migraine | Diagnosis of migraine, by the ICHD-3 criteria. Age between 18 and 60 years. Female and males. Right-handed Receives: Drug: Nitroglycerin 0.3 MG; Diagnostic Test: MRI; Diagnostic Test: Blood sampling; Device: Sleep profiler | |
| Healthy controls | Age between 18 and 60 years. Female and males. Right-handed Receives: Drug: Nitroglycerin 0.3 MG; Diagnostic Test: MRI; Diagnostic Test: Blood sampling; Device: Sleep profiler |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline glymphatic function after nitroglycerin administration
The DTI-ALPS index will be quantified before and after nitroglycerin administration as an indirect measure of the glymphatic function
Measured: Up to 8 hours
Secondary outcomes (2)
Change from baseline plasma levels of neuropeptides after nitroglycerin administration
ELISA kits will be used to measure the plasma level of neuropeptides involved in migraine pathophysiology before and after nitroglycerin administration
Measured: Up to 8 hours
Change from baseline sleep architecture after nitroglycerin administration
Sleep Architecture will be studied through the Sleep Profiler before and after nitroglycerin administration
Measured: Up to 8 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2023
- Study start30 Apr 2023
- Primary completion30 Mar 2027 (estimated)
- Study completion4 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MigraineStudies of the same condition, open and under way.
- More trials run by IRCCS San RaffaeleThe sponsor's other registered studies.
- 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
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Roberta Messina, IRCCS San Raffaele
- Investigators
- Roberta Messina, MD, PhD, Principal investigator, IRCCS San Raffaele Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05907655
- Sponsor's protocol ID
- GR-2021-12374851
- Status last verified
- Nov 2026
- First submitted
- 16 May 2023
- Last updated
- 6 Nov 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Discovering the Functional Role of the Glymphatic System in the Genesis of the Migraine Attack
- ClinicalTrials.gov ID
- NCT05907655
- Acronym / sponsor ID
- GR-2021-12374851
- Conditions
- Migraine
- Keywords
- migraine, MRI, glymphatic system, sleep, neuropeptides
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- IRCCS San RaffaeleUniversity, hospital or other
- Study start
- 30 Apr 2023 (actual)
- Primary completion
- 30 Mar 2027 (estimated)
- Study completion
- 4 Apr 2027 (estimated)
- First posted
- 18 Jun 2023 (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.
This study aimed to investigate the role of the glymphatic system in the initiation of migraine attacks, using non-invasive magnetic resonance imaging techniques and a validated model of migraine induction by nitroglycerin administration. Secondarily, the relationship between the function of the glymphatic system during nitroglycerin-induced migraine attacks and sleep architecture and plasma levels of migraine-involved neuropeptides will be investigated.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Adult patients with migraine | – | Drug: Nitroglycerin 0.3 MG, Diagnostic Test: MRI, Diagnostic Test: Blood sampling, Device: Sleep profilerDiagnosis of migraine, by the ICHD-3 criteria. Age between 18 and 60 years. Female and males. Right-handed |
| Healthy controls | – | Drug: Nitroglycerin 0.3 MG, Diagnostic Test: MRI, Diagnostic Test: Blood sampling, Device: Sleep profilerAge between 18 and 60 years. Female and males. Right-handed |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Patients with a diagnosis of episodic migraine without aura, by the standard ICHD diagnostic criteria, will be prospectively recruited. Patients will be allowed to take only one migraine preventive treatment at a stable dose during the study. Healthy controls suffering from any headaches with the exception of infrequent tension-type headache will be excluded from the study.
Key inclusion criteria (5 listed)
- Diagnosis of migraine, by the ICHD-3 criteria;
- Age between 18 and 60 years;
- Willing and able to comply with scheduled visits.
Key exclusion criteria (24 listed)
- Overuse of acute medications for headache;
- Continuous or daily headache;
- Other primary headache disorders, with the exception of infrequent tension-type headache.
- Any subject with frequent tension type headache, migraine, cluster headache, other pain syndromes or neurological conditions.
- Allergy to nitroglycerin;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nitroglycerin 0.3 MGSublingual nitroglycerin will be used to provoke spontaneous-like migraine attacks in migraine patients. A dose of 0.9 mg of sublingual nitroglycerin will be used. The same dose will be administrated to controls. | Drug | Adult patients with migraine, Healthy controls |
| MRIThe following brain MRI sequences will be acquired before and after nitroglycerin administration: fluid attenuated inversion recovery (FLAIR), 3D T1-weighted inversion recovery prepared gradient echo, diffusion weighted sequence and 3D susceptibility weighted images. | Diagnostic test | Adult patients with migraine, Healthy controls |
| Blood samplingPlasma levels of neuropeptides involed in migraine will be measured using commercially available enzyme-linked immune-sorbent assay (ELISA) kits. All ELISA will be performed by the same experienced technician who will be blinded for the clinical diagnosis. | Diagnostic test | Adult patients with migraine, Healthy controls |
| Sleep profilerSleep architecture will be investigated using the Sleep Profiler. Sleep Profiler is medical device with CE mark which is produced by Advanced Brain Monitoring and distributed throughout Italy exclusively by Medigas. Sleep staging will be automatically performed for 30-second epochs throughout a dedicated software and a standardized and validated procedure. Frontopolar EEG signal waveforms will be visually inspected to confirm the accuracy of the auto-staging. | Device | Adult patients with migraine, Healthy controls |
Primary outcome
Change from baseline glymphatic function after nitroglycerin administration
Time frame: Up to 8 hours
The DTI-ALPS index will be quantified before and after nitroglycerin administration as an indirect measure of the glymphatic function
2 secondary outcomes
Change from baseline plasma levels of neuropeptides after nitroglycerin administration
Time frame: Up to 8 hours
Change from baseline sleep architecture after nitroglycerin administration
Time frame: Up to 8 hours
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2026.
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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.
Roberta Messina, MD, PhD principal investigator
IRCCS San Raffaele Hospital
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 San Raffaele 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 24 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: looking for participants now, as of the sponsor's last update on 6 Nov 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Roberta Messina, MD, PhD (00390226433944, messina.roberta@hsr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline glymphatic function after nitroglycerin administration (time frame: Up to 8 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Nov 2026.