Study of the Glymphatic System in Migraine

Recruiting

• Conditions: Migraine
• Interventions: Drug: Nitroglycerin 0.3 MG; Diagnostic Test: MRI; Diagnostic Test: Blood sampling; Device: Sleep profiler

• Registration Number: NCT05907655
• Lead Sponsor: IRCCS San Raffaele

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2023-04-30
• Study First Submitted: 2023-05-16
• Status Verified: 2023-06
• Study First Submitted QC: 2023-06-07
• Last Update Submitted: 2023-06-16
• Study First Posted: 2023-06-18
• Last Update Posted: 2023-06-22
• Primary Completion: 2025-06-30
• Study Completion: 2026-04-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

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.

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Adult patients with migraine	MRI	Diagnosis of migraine, by the ICHD-3 criteria. Age between 18 and 60 years. Female and males. Right-handed
Adult patients with migraine	Blood sampling	Diagnosis of migraine, by the ICHD-3 criteria. Age between 18 and 60 years. Female and males. Right-handed
Adult patients with migraine	Sleep profiler	Diagnosis of migraine, by the ICHD-3 criteria. Age between 18 and 60 years. Female and males. Right-handed
Healthy controls	Nitroglycerin 0.3 MG	Age between 18 and 60 years. Female and males. Right-handed
Healthy controls	MRI	Age between 18 and 60 years. Female and males. Right-handed
Healthy controls	Blood sampling	Age between 18 and 60 years. Female and males. Right-handed
Adult patients with migraine	Nitroglycerin 0.3 MG	Diagnosis of migraine, by the ICHD-3 criteria. Age between 18 and 60 years. Female and males. Right-handed
Healthy controls	Sleep profiler	Age between 18 and 60 years. Female and males. Right-handed

Primary Outcome Measures

Name	Time	Method
Change from baseline glymphatic function after nitroglycerin administration	Up to 8 hours	The DTI-ALPS index will be quantified before and after nitroglycerin administration as an indirect measure of the glymphatic function

Secondary Outcome Measures

Name	Time	Method
Change from baseline plasma levels of neuropeptides after nitroglycerin administration	Up to 8 hours	ELISA kits will be used to measure the plasma level of neuropeptides involved in migraine pathophysiology before and after nitroglycerin administration
Change from baseline sleep architecture after nitroglycerin administration	Up to 8 hours	Sleep Architecture will be studied through the Sleep Profiler before and after nitroglycerin administration

Trial Locations

Locations (1)

IRCCS San Raffaele Hospital; 🇮🇹 Milan, Italy