Glymphatic SystemNCT06335004
Evaluation of Brain Waste Clearance Pathways Using Magnetic Resonance Imaging in Pediatric Patients With White Matter Diseases
An observational study of Glymphatic System and White Matter Disease, run by IRCCS Eugenio Medea at 1 site in Italy.
Trial summary
The dilation of perivascular spaces can be the result of various etiopathogenetic processes. White matter atrophy can cause enlargement of these perivascular spaces (PVS) but also obstruction of fluid drainage systems (interstitial fluid, ISF) and metabolites, as evidenced by some recent studies. Read more about this study
- Who is it for?
- Ages 9 months to 70 years
- Conditions the study is for
- Glymphatic System, White Matter Disease, Pediatric Disorder
- What is being tested?
- Magnetic resonance imaging
- Type of treatment
- Injection or infusion
- How many people
- 100 participants
- Where
- 1 siteItaly
- Study dates
- 1 Mar 2022to 28 Feb 2025
- 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 9 months to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients with white matter disease on T2 and FLAIR sequences are included in this study. New MR sequences that can further identify subtle signal intensity changes within these white matter lesions will allow to further characterise them. Some patients will require intravenous gadolinium as part of their diagnostic MR work-up. Research MR sequences will also be acquired after gadolinium admininstration to further improve characterisation of the composition of white matter lesions.
Who may be able to join
- patients with and without white matter disease
- patients willing to participate in research with signed consent form
- no age limit (results will be age matched)
Who cannot join
- unwilling to participate in research
Trial locations and contacts
1 site in 1 country.
Italy1 site
Scientific Institute IRCCS Eugenio Medea
Bosisio Parini, Lecco, 23842
About this study
Official title: Valutazione Delle Vie "Glinfatiche" Utilizzando la Risonanza Magnetica Nelle Malattie Della Sostanza Bianca
The dilation of perivascular spaces can be the result of various etiopathogenetic processes. White matter atrophy can cause enlargement of these perivascular spaces (PVS) but also obstruction of fluid drainage systems (interstitial fluid, ISF) and metabolites, as evidenced by some recent studies. Focal stagnation of liquids and deposition of toxic material induce tissue hypoxia and neuroglial dysfunction. Dilation of PVS can be associated with changes in white matter and microhemorrhages. We want to study these etiopathogenetic phenomena by implementing specific MRI methods.
Read the detailed description
Primary objective: the quantification of indirect magnetic resonance markers of altered waste drainage systems using validated scales in patients with white matter disease. Secondary objective: the evaluation of white matter alterations in relation to the known anatomical glymphatic pathways by analyzing both structural and diffusion data.
- Being tested
- Magnetic resonance imaging
- Keywords
- Glymphatic system, white matter disease, perivascular space, diffusion tensor imaging, gadolinium, rare disease
- Medical subject headings
- Leukoencephalopathies, Rare Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magnetic resonance imagingDiagnostic test
Patients will undergo a magnetic resonance imaging for clinical purposes to which additional sequences. Post gadolinium research sequences will be acquired only if intravenous gadolinium needs to be administered for clinical purposes.
| Study group | Role | What they receive |
|---|---|---|
| Patients with white matter disease/healthy subjects | Patients with white matter disease due to genetic or acquired causes. MRI with or without intravenous gadolinium will be performed Receives: Diagnostic Test: Magnetic resonance imaging | |
| Patients with no white matter disease | Patients undergoing MRI with or without gadolinium for clinical diagnostic purposes, with no known white matter disease. Receives: Diagnostic Test: Magnetic resonance imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
Extent of white matter lesions
T1 values of lesions
Measured: once at recruitment
Number of perivascular spaces
count of perivascular spaces and total volume in disease population
Measured: once at recruitment
Volume of parasagittal dural space
volume of parasagittal dural space in disease population
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 posted28 Mar 2024
- Study start1 Mar 2022
- Primary completion31 Dec 2024 (estimated)
- Study completion28 Feb 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Glymphatic SystemStudies 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
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06335004
- Sponsor's protocol ID
- 926
- Status last verified
- Mar 2024
- First submitted
- 5 May 2022
- Last updated
- 28 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, Lindley RI, O'Brien JT, Barkhof F, Benavente OR, Black SE, Brayne C, Breteler M, Chabriat H, Decarli C, de Leeuw FE, Doubal F, Duering M, Fox NC, Greenberg S, Hachinski V, Kilimann I, Mok V, Oostenbrugge Rv, Pantoni L, Speck O, Stephan BC, Teipel S, Viswanathan A, Werring D, Chen C, Smith C, van Buchem M, Norrving B, Gorelick PB, Dichgans M; STandards for ReportIng Vascular changes on nEuroimaging (STRIVE v1). Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013 Aug;12(8):822-38. doi: 10.1016/S1474-4422(13)70124-8.
PubMed 23867200Ma YJ, Fan S, Shao H, Du J, Szeverenyi NM, Young IR, Bydder GM. Use of Multiplied, Added, Subtracted and/or FiTted Inversion Recovery (MASTIR) pulse sequences. Quant Imaging Med Surg. 2020 Jun;10(6):1334-1369. doi: 10.21037/qims-20-568.
PubMed 32550142Ma YJ, Shao H, Fan S, Lu X, Du J, Young IR, Bydder GM. New options for increasing the sensitivity, specificity and scope of synergistic contrast magnetic resonance imaging (scMRI) using Multiplied, Added, Subtracted and/or FiTted (MASTIR) pulse sequences. Quant Imaging Med Surg. 2020 Oct;10(10):2030-2065. doi: 10.21037/qims-20-795.
PubMed 33014733Naganawa S, Nakane T, Kawai H, Taoka T. Lack of Contrast Enhancement in a Giant Perivascular Space of the Basal Ganglion on Delayed FLAIR Images: Implications for the Glymphatic System. Magn Reson Med Sci. 2017 Apr 10;16(2):89-90. doi: 10.2463/mrms.ci.2016-0114. Epub 2017 Jan 25. No abstract available.
PubMed 28123166Rasmussen MK, Mestre H, Nedergaard M. The glymphatic pathway in neurological disorders. Lancet Neurol. 2018 Nov;17(11):1016-1024. doi: 10.1016/S1474-4422(18)30318-1.
PubMed 30353860Hawkes CA, Hartig W, Kacza J, Schliebs R, Weller RO, Nicoll JA, Carare RO. Perivascular drainage of solutes is impaired in the ageing mouse brain and in the presence of cerebral amyloid angiopathy. Acta Neuropathol. 2011 Apr;121(4):431-43. doi: 10.1007/s00401-011-0801-7. Epub 2011 Jan 23.
PubMed 21259015
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Valutazione Delle Vie "Glinfatiche" Utilizzando la Risonanza Magnetica Nelle Malattie Della Sostanza Bianca
- ClinicalTrials.gov ID
- NCT06335004
- Acronym / sponsor ID
- 926
- Keywords
- Glymphatic system, white matter disease, perivascular space, diffusion tensor imaging, gadolinium, rare disease
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- IRCCS Eugenio MedeaUniversity, hospital or other
- Study start
- 1 Mar 2022 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 28 Feb 2025 (estimated)
- First posted
- 28 Mar 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 dilation of perivascular spaces can be the result of various etiopathogenetic processes. White matter atrophy can cause enlargement of these perivascular spaces (PVS) but also obstruction of fluid drainage systems (interstitial fluid, ISF) and metabolites, as evidenced by some recent studies. Focal stagnation of liquids and deposition of toxic material induce tissue hypoxia and neuroglial dysfunction. Dilation of PVS can be associated with changes in white matter and microhemorrhages. We want to study these etiopathogenetic phenomena by implementing specific MRI methods.
Detailed description
Primary objective: the quantification of indirect magnetic resonance markers of altered waste drainage systems using validated scales in patients with white matter disease. Secondary objective: the evaluation of white matter alterations in relation to the known anatomical glymphatic pathways by analyzing both structural and diffusion data.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with white matter disease/healthy subjects | – | Diagnostic Test: Magnetic resonance imagingPatients with white matter disease due to genetic or acquired causes. MRI with or without intravenous gadolinium will be performed |
| Patients with no white matter disease | – | Diagnostic Test: Magnetic resonance imagingPatients undergoing MRI with or without gadolinium for clinical diagnostic purposes, with no known white matter disease. |
Who may qualify
- Ages
- 9 months to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with white matter disease on T2 and FLAIR sequences are included in this study. New MR sequences that can further identify subtle signal intensity changes within these white matter lesions will allow to further characterise them. Some patients will require intravenous gadolinium as part of their diagnostic MR work-up. Research MR sequences will also be acquired after gadolinium admininstration to further improve characterisation of the composition of white matter lesions.
Key inclusion criteria (3 listed)
- patients with and without white matter disease
- patients willing to participate in research with signed consent form
- no age limit (results will be age matched)
Key exclusion criteria (1 listed)
- unwilling to participate in research
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 imagingPatients will undergo a magnetic resonance imaging for clinical purposes to which additional sequences. Post gadolinium research sequences will be acquired only if intravenous gadolinium needs to be administered for clinical purposes. | Diagnostic test | Patients with no white matter disease, Patients with white matter disease/healthy subjects |
Primary outcome
Extent of white matter lesions
Time frame: once at recruitment
T1 values of lesions
Number of perivascular spaces
Time frame: once at recruitment
count of perivascular spaces and total volume in disease population
Volume of parasagittal dural space
Time frame: once at recruitment
volume of parasagittal dural space in disease population
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2024.
- Results publication: PubMed 23867200Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, Lindley RI, O'Brien JT, Barkhof F, Benavente OR, Black SE, Brayne C, Breteler M, Chabriat H, Decarli C, de Leeuw FE, Doubal F, Duering M, Fox NC, Greenberg S, Hachinski V, Kilimann I, Mok V, Oostenbrugge Rv, Pantoni L, Speck O, Stephan BC, Teipel S, Viswanathan A, Werring D, Chen C, Smith C, van Buchem M, Norrving B, Gorelick PB, Dichgans M; STandards for ReportIng Vascular changes on nEuroimaging (STRIVE v1). Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013 Aug;12(8):822-38. doi: 10.1016/S1474-4422(13)70124-8.
- Results publication: PubMed 32550142Ma YJ, Fan S, Shao H, Du J, Szeverenyi NM, Young IR, Bydder GM. Use of Multiplied, Added, Subtracted and/or FiTted Inversion Recovery (MASTIR) pulse sequences. Quant Imaging Med Surg. 2020 Jun;10(6):1334-1369. doi: 10.21037/qims-20-568.
- Results publication: PubMed 33014733Ma YJ, Shao H, Fan S, Lu X, Du J, Young IR, Bydder GM. New options for increasing the sensitivity, specificity and scope of synergistic contrast magnetic resonance imaging (scMRI) using Multiplied, Added, Subtracted and/or FiTted (MASTIR) pulse sequences. Quant Imaging Med Surg. 2020 Oct;10(10):2030-2065. doi: 10.21037/qims-20-795.
- Results publication: PubMed 28123166Naganawa S, Nakane T, Kawai H, Taoka T. Lack of Contrast Enhancement in a Giant Perivascular Space of the Basal Ganglion on Delayed FLAIR Images: Implications for the Glymphatic System. Magn Reson Med Sci. 2017 Apr 10;16(2):89-90. doi: 10.2463/mrms.ci.2016-0114. Epub 2017 Jan 25. No abstract available.
- Results publication: PubMed 30353860Rasmussen MK, Mestre H, Nedergaard M. The glymphatic pathway in neurological disorders. Lancet Neurol. 2018 Nov;17(11):1016-1024. doi: 10.1016/S1474-4422(18)30318-1.
- Results publication: PubMed 21259015Hawkes CA, Hartig W, Kacza J, Schliebs R, Weller RO, Nicoll JA, Carare RO. Perivascular drainage of solutes is impaired in the ageing mouse brain and in the presence of cerebral amyloid angiopathy. Acta Neuropathol. 2011 Apr;121(4):431-43. doi: 10.1007/s00401-011-0801-7. Epub 2011 Jan 23.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
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 Glymphatic System and White Matter Disease, 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 3 inclusion and 1 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 28 Mar 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?
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?
Extent of white matter lesions (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?
On the ClinicalTrials.gov record for NCT06335004, which also lists 6 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 28 Mar 2024.