NeuroinflammationI-CLEANEDNCT06432023
Imaging - Clinical Evaluation of Altered Nervous System Drainage
An observational study of Neuroinflammation and Autism Spectrum Disorder, run by IRCCS Eugenio Medea at 1 site in Italy.
Trial summary
The current study aims to evaluate the aspects of perfusion, fluid diffusivity in the interstitium and the T1 and T2 signal of the PVS and WMH. The current study has the following objectives: a) evaluate the perfusion aspects using the gadolinium-based contrast medium of brain tissues in the short term; b) the… Read more about this study
- Who is it for?
- Ages 2 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Neuroinflammation, Autism Spectrum Disorder
- What is being tested?
- Magnetic resonance imaging
- How many people
- 100 participants
- Where
- 1 siteItaly
- Study dates
- 1 Oct 2023to 31 Jan 2026
- 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 2 to 75 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Patients with obvious white matter disease on T2 and FLAIR sequences will be included in this study. In particular patients with recent diagnosis of autism spectrum disorder, traumatic brain injury, Steinert's muscular dystrophy will be included.
Who may be able to join
- patients with white matter lesions and/or enlarged perivascular spaces
Who cannot join
- have contraindications to the use of contrast medium;
- are clinically unstable patients and prolonged sedation is inappropriate
- have tumors
- contraindications to perform MR.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Scientific Institute IRCCS E. Medea
Bosisio Parini, Lecco, 23842
Nivedita Agarwal, MD, +39 031855 ext. 398, nivedita.agarwal@lanostrafamiglia.it
Noemi Miscioscia, noemi.miscioscia@lanostrafamiglia.it
About this study
Official title: Multi-signal Analysis of the Composition and Movement of Fluid in Various Cerebral Compartments in Healthy Subjects and Subjects With White Matter Pathology
The current study aims to evaluate the aspects of perfusion, fluid diffusivity in the interstitium and the T1 and T2 signal of the PVS and WMH. The current study has the following objectives: a) evaluate the perfusion aspects using the gadolinium-based contrast medium of brain tissues in the short term; b) the direction of flow of fluids at very low speed in the white matter using the DTI sequences configured for this purpose; c) T1-mapping of the lesions of interest.
The expected results will help us understand two aspects of neurofluid dynamics: a) how the fluid moves within the central nervous system in the first minutes after the injection of the tracer (in our case the gadolinium-based contrast medium) and b) what is the composition of the fluid within the PVS and WMH and how can investigators characterize them more accurately.
Read the detailed description
Among the various indirect markers of altered drainage of neuroglial waste metabolites, there is the widening of the perivascular spaces (PVS) and the presence of white matter signal alterations.
An increase in the number of PVS and their enlargement could represent an indirect marker of obstruction to the drainage of fluids and solutes along the arterial wall at the level of the white matter. This obstruction would also be the basis of tissue hypoxia resulting in the formation of areas of signal hyperintensity in the white matter (White Matter Hyperintensities, WMH) often observed in patients with neurodegenerative diseases and small vessel disease.
It is currently unclear what the main drainage route of brain waste metabolites is. Surely there are at least two.
The glymphatic theory proposes the entry of the cerebrospinal fluid (CSF) from the subarachnoid space towards the brain parenchyma in a centripetal direction and exit of the metabolic waste along the perivenous spaces. The drainage of metabolic waste could also be explained by the more recent "intramural periarterial drainage" (IPAD) theory which shows elimination along the arterial walls in a centrifugal direction.
In magnetic resonance imaging (MRI), the study of solute drainage requires a dynamic evaluation, which is able to evaluate the temporal movement of a tracer. There are several MRI techniques, already described in the literature, which can be used to obtain information relating to perfusion processes and the coupling of neuronal and vascular activity in different brain areas.
The circulation of CSF is well known, which is produced largely at the level of the choroid plexuses and is then partly reabsorbed by the arachnoid granulations at the level of the subarachnoid space. Recent studies demonstrate that the CSF re-enters the brain parenchyma in a centripetal manner, crossing the thickness of the gray matter and then the white matter. This movement is regulated by various factors, and in particular by the activity of the smooth muscle cells of the arterial walls, the aquaporin 4 receptors (water channels) and by the chemical-physical properties of the extracellular matrix in the extracellular space.
- Conditions
- Neuroinflammation, Autism Spectrum Disorder
- Being tested
- Magnetic resonance imaging
- Keywords
- magnetic resonance imaging, autism spectrum disorder, white matter disease, glymphatic system, brain waste clearance
- Medical subject headings
- Neuroinflammatory Diseases, Autism Spectrum Disorder, Leukoencephalopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magnetic resonance imagingDiagnostic test
Diagnostic and research scanning using magnetic resonance imaging.
| Study group | Role | What they receive |
|---|---|---|
| Patients | patients with white matter hyperintensities, patients with enlarged perivascular spaces, Focus will be on patients with a clinical diagnosis of muscular dystrophy or autism spectrum disorder or traumatic brain injury. Receives: Diagnostic Test: Magnetic resonance imaging | |
| Controls | Patients who need a diagnostic scan but do not carry a diagnosis of psychomotor or cognitive impairment or without a history of TBI and tumors. No white matter hyperintensities. Receives: Diagnostic Test: Magnetic resonance imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
Perivascular space count
Number and distribution of enlarged perivascular spaces
Measured: once at recruitment
Volume of parasagittal dura
correlation of parasagittal dura and perivascular count
Measured: once at recruitment
fMRI signal during sedation
effect of sedation on BOLD signal
Measured: once at recruitment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2024
- Study start1 Oct 2023
- Primary completion31 Oct 2025 (estimated)
- Study completion31 Jan 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeuroinflammationStudies of the same condition, open and under way.
- More trials run by IRCCS Eugenio MedeaThe 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS Eugenio Medea
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health, Italy
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06432023
- Sponsor's protocol ID
- 1022
- Acronym
- I-CLEANED
- Status last verified
- May 2024
- First submitted
- 15 May 2024
- Last updated
- 29 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-signal Analysis of the Composition and Movement of Fluid in Various Cerebral Compartments in Healthy Subjects and Subjects With White Matter Pathology
- ClinicalTrials.gov ID
- NCT06432023
- Acronym / sponsor ID
- I-CLEANED / 1022
- Conditions
- Neuroinflammation, Autism Spectrum Disorder
- Keywords
- magnetic resonance imaging, autism spectrum disorder, white matter disease, glymphatic system, brain waste clearance
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- IRCCS Eugenio MedeaUniversity, hospital or other
- Collaborators
- Ministry of Health, Italy
- Study start
- 1 Oct 2023 (actual)
- Primary completion
- 31 Oct 2025 (estimated)
- Study completion
- 31 Jan 2026 (estimated)
- First posted
- 29 May 2024 (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 current study aims to evaluate the aspects of perfusion, fluid diffusivity in the interstitium and the T1 and T2 signal of the PVS and WMH. The current study has the following objectives: a) evaluate the perfusion aspects using the gadolinium-based contrast medium of brain tissues in the short term; b) the direction of flow of fluids at very low speed in the white matter using the DTI sequences configured for this purpose; c) T1-mapping of the lesions of interest.
The expected results will help us understand two aspects of neurofluid dynamics: a) how the fluid moves within the central nervous system in the first minutes after the injection of the tracer (in our case the gadolinium-based contrast medium) and b) what is the composition of the fluid within the PVS and WMH and how can investigators characterize them more accurately.
Detailed description
Among the various indirect markers of altered drainage of neuroglial waste metabolites, there is the widening of the perivascular spaces (PVS) and the presence of white matter signal alterations.
An increase in the number of PVS and their enlargement could represent an indirect marker of obstruction to the drainage of fluids and solutes along the arterial wall at the level of the white matter. This obstruction would also be the basis of tissue hypoxia resulting in the formation of areas of signal hyperintensity in the white matter (White Matter Hyperintensities, WMH) often observed in patients with neurodegenerative diseases and small vessel disease.
It is currently unclear what the main drainage route of brain waste metabolites is. Surely there are at least two.
The glymphatic theory proposes the entry of the cerebrospinal fluid (CSF) from the subarachnoid space towards the brain parenchyma in a centripetal direction and exit of the metabolic waste along the perivenous spaces. The drainage of metabolic waste could also be explained by the more recent "intramural periarterial drainage" (IPAD) theory which shows elimination along the arterial walls in a centrifugal direction.
In magnetic resonance imaging (MRI), the study of solute drainage requires a dynamic evaluation, which is able to evaluate the temporal movement of a tracer. There are several MRI techniques, already described in the literature, which can be used to obtain information relating to perfusion processes and the coupling of neuronal and vascular activity in different brain areas.
The circulation of CSF is well known, which is produced largely at the level of the choroid plexuses and is then partly reabsorbed by the arachnoid granulations at the level of the subarachnoid space. Recent studies demonstrate that the CSF re-enters the brain parenchyma in a centripetal manner, crossing the thickness of the gray matter and then the white matter. This movement is regulated by various factors, and in particular by the activity of the smooth muscle cells of the arterial walls, the aquaporin 4 receptors (water channels) and by the chemical-physical properties of the extracellular matrix in the extracellular space.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients | – | Diagnostic Test: Magnetic resonance imagingpatients with white matter hyperintensities, patients with enlarged perivascular spaces, Focus will be on patients with a clinical diagnosis of muscular dystrophy or autism spectrum disorder or traumatic brain injury. |
| Controls | – | Diagnostic Test: Magnetic resonance imagingPatients who need a diagnostic scan but do not carry a diagnosis of psychomotor or cognitive impairment or without a history of TBI and tumors. No white matter hyperintensities. |
Who may qualify
- Ages
- 2 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with obvious white matter disease on T2 and FLAIR sequences will be included in this study. In particular patients with recent diagnosis of autism spectrum disorder, traumatic brain injury, Steinert's muscular dystrophy will be included.
Key inclusion criteria (1 listed)
- patients with white matter lesions and/or enlarged perivascular spaces
Key exclusion criteria (4 listed)
- have contraindications to the use of contrast medium;
- are clinically unstable patients and prolonged sedation is inappropriate
- have tumors
- contraindications to perform MR.
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 |
|---|---|---|
| Magnetic resonance imagingDiagnostic and research scanning using magnetic resonance imaging. | Diagnostic test | Controls, Patients |
Primary outcome
Perivascular space count
Time frame: once at recruitment
Number and distribution of enlarged perivascular spaces
Volume of parasagittal dura
Time frame: once at recruitment
correlation of parasagittal dura and perivascular count
fMRI signal during sedation
Time frame: once at recruitment
effect of sedation on BOLD signal
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2024.
- Individual participant dataSharing planned: Undecided
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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.
Scientific Institute IRCCS E. Medea
Bosisio Parini, Italy
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 Neuroinflammation and Autism Spectrum Disorder, run by IRCCS Eugenio Medea 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 1 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 29 May 2024. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Perivascular space count (time frame: once at recruitment). The study lists 3 primary outcomes in all. 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 29 May 2024.