Study of the Glymphatic System in Migraine

Migraine Clinical Trial

Official title:

Discovering the Functional Role of the Glymphatic System in the Genesis of the Migraine Attack

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05907655
• Other study ID #: GR-2021-12374851
• Status: Recruiting
• Start date: April 30, 2023
• Est. completion date: April 30, 2026

Study information

• Verified date: June 2023
• Source: IRCCS San Raffaele
• Contact: Roberta Messina, MD, PhD
• Phone: 00390226433944
• Email: messina.roberta[@]hsr.it
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: April 30, 2026
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

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. Exclusion criteria

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.

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.

Related Conditions & MeSH terms

• Migraine
• Migraine Disorders

Intervention

Drug:
• Nitroglycerin 0.3 MG
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.

Diagnostic Test:
• MRI
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 sampling
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.

Device:
• Sleep profiler
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.

Locations

Country	Name	City	State
Italy	IRCCS San Raffaele Hospital	Milan

Sponsors (1)

Lead Sponsor	Collaborator
IRCCS San Raffaele

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Up to 8 hours
Secondary	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	Up to 8 hours
Secondary	Change from baseline sleep architecture after nitroglycerin administration	Sleep Architecture will be studied through the Sleep Profiler before and after nitroglycerin administration	Up to 8 hours