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Glymphatic SystemNCT05035251

Glymphatic Pathway in Brain Imaging

An observational study of Glymphatic System, run by Paracelsus Medical University at 1 site in Germany.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

To investigate the pathways of Gadolinium-based contrast agent (GBCA) in different brain compartments and evaluate correlations of GBCA enhancement with specific diseases. Read more about this study

Who is it for?
Ages 18 to 90 years
Conditions the study is for
Glymphatic System
How many people
60 participants
Where
1 siteGermany
Study dates
1 Jul 2020to 1 Dec 2024
How long will I take part?
2 Years
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 18 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: The study population will be patients of a primary care clinic.

Who may be able to join

  • Only patients with a clinical indication for GBCA
  • Written informed consent
  • No allergies to GBCA

Who cannot join

  • Contraindications for MRI

Trial locations and contacts

1 site in 1 country.

Germany1 site, 1 recruiting

  • Institute of Radiology and Nuclear Medicine

    Nuremberg, Bavaria, 90419

    Panagiota Manava, Dr., +49 911 398 114930, panagiota.manava@klinikum-nuernberg.de

    Michael M. Lell, Prof. Dr., +49 911 398 2540, michael.lell@klinikum-nuernberg.de

    Recruiting

Other trials in Germany

About this study

Official title: Glymphatic Pathway in Brain Imaging: Evaluation of MRI Findings

To investigate the pathways of Gadolinium-based contrast agent (GBCA) in different brain compartments and evaluate correlations of GBCA enhancement with specific diseases.

Read the detailed description

To investigate the contrast enhancement in different brain compartments. Until recently, it had been assumed that Gadolinium-based contrast agents do not cross the blood-brain barrier, but delayed imaging revealed signal increase in a number of compartments in the CSF (the perilymph of the inner ear, the internal auditory canal, the Meckel's cave, the suprasellar cistern, the ambient cistern and anterior eye compartment). These findings suggested, that Gadolinium-based contrast agents (GBCA) penetrate into the CSF through the choroid plexus and the aqueous chamber of the eye. MRI has provided the evidence of presence of meningeal lymphatic vessels in human and non-human primates for central nervous system waste clearance. It has been demonstrated that heavily T2-weighted fluid-attenuated inversion recovery (hT2w-FLAIR) MRI detects even very low concentrations of GBCA in the CSF.

The aim of our study is to find specific enhancement patterns in various cerebral compartments in correlation with specific diseases and procedures such as radiation, surgery and drug application in delayed gadolinium imaging. Only patients with a clinical indication for GBCA will be included in this prospective study. Before enrollment, each patient will have provided written informed consent of participation and publication prior to inclusion to the observational study. The scan will be performed as baseline before intravenous contrast administration of a single dose of gadoteric acid 20 minutes and 120 minutes after contrast administration. Whole-brain image stacks will be analyzed on patient basis. Regions of interest for signal intensity measurements will be drawn in various cerebral fluid spaces, the size of the region of interest will depend on the target structure. The following structures should be measured: lateral and central aqueous chamber and vitreous body of the eye, distal optic nerve sheath, Meckel's cave, lateral ventricles and basal cisterns.

Data will be expressed as mean values +/- one-fold standard deviation (SD). The normality of data distribution will be assessed using Levene's test. Data showing a Gaussian distribution will be evaluated by an analysis of variances (ANOVA) with a post-hoc analysis. Estimated sample size is around 30 patients in the control and the experimental group. Cases with missing or unavailable data will be excluded.

Keywords
glymphatic system, imaging of blood brain barrier

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT05035251
Study groupRoleWhat they receive
experimentalpatients with a condition
controlpatients without condition

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change of Signal-Intensity (SI)-Measurements with ROI in 3 specific MRI Scans

    Regions of interest for signal intensity measurements will be drawn in various cerebral fluid spaces, the size of the region of interest will depend on the target structure. Following structures will be measured: lateral and central aqueous chamber and vitreous body of the eye, distal optic nerve sheath, Meckel's cave, lateral ventricles and basal cisterns.

    Measured: Baseline (nativ scan), 20 minutes and 120 minutes after contrast media application

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Sep 2021
  2. Study start1 Jul 2020
  3. Primary completion11 Nov 2024 (estimated)
  4. Study completion1 Dec 2024 (estimated)

Resources

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
60 participants (estimated)
Target duration
2 Years
IDs, dates and publications
ClinicalTrials.gov ID
NCT05035251
Sponsor's protocol ID
GP_2021_KNN
Status last verified
Nov 2023
First submitted
25 Aug 2021
Last updated
22 Nov 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Deike-Hofmann K, Reuter J, Haase R, Paech D, Gnirs R, Bickelhaupt S, Forsting M, Heussel CP, Schlemmer HP, Radbruch A. Glymphatic Pathway of Gadolinium-Based Contrast Agents Through the Brain: Overlooked and Misinterpreted. Invest Radiol. 2019 Apr;54(4):229-237. doi: 10.1097/RLI.0000000000000533.

    PubMed 30480554

  • Taoka T, Naganawa S. Gadolinium-based Contrast Media, Cerebrospinal Fluid and the Glymphatic System: Possible Mechanisms for the Deposition of Gadolinium in the Brain. Magn Reson Med Sci. 2018 Apr 10;17(2):111-119. doi: 10.2463/mrms.rev.2017-0116. Epub 2018 Jan 25.

    PubMed 29367513

  • Absinta M, Ha SK, Nair G, Sati P, Luciano NJ, Palisoc M, Louveau A, Zaghloul KA, Pittaluga S, Kipnis J, Reich DS. Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI. Elife. 2017 Oct 3;6:e29738. doi: 10.7554/eLife.29738.

    PubMed 28971799

  • Rennels ML, Gregory TF, Blaumanis OR, Fujimoto K, Grady PA. Evidence for a 'paravascular' fluid circulation in the mammalian central nervous system, provided by the rapid distribution of tracer protein throughout the brain from the subarachnoid space. Brain Res. 1985 Feb 4;326(1):47-63. doi: 10.1016/0006-8993(85)91383-6.

    PubMed 3971148

  • Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, Benveniste H, Vates GE, Deane R, Goldman SA, Nagelhus EA, Nedergaard M. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid beta. Sci Transl Med. 2012 Aug 15;4(147):147ra111. doi: 10.1126/scitranslmed.3003748.

    PubMed 22896675

  • Bedussi B, Almasian M, de Vos J, VanBavel E, Bakker EN. Paravascular spaces at the brain surface: Low resistance pathways for cerebrospinal fluid flow. J Cereb Blood Flow Metab. 2018 Apr;38(4):719-726. doi: 10.1177/0271678X17737984. Epub 2017 Oct 17.

    PubMed 29039724

  • Smith AJ, Yao X, Dix JA, Jin BJ, Verkman AS. Test of the 'glymphatic' hypothesis demonstrates diffusive and aquaporin-4-independent solute transport in rodent brain parenchyma. Elife. 2017 Aug 21;6:e27679. doi: 10.7554/eLife.27679.

    PubMed 28826498

  • Dobson H, Sharp MM, Cumpsty R, Criswell TP, Wellman T, Finucane C, Sullivan JM, Weller RO, Verma A, Carare RO. The perivascular pathways for influx of cerebrospinal fluid are most efficient in the midbrain. Clin Sci (Lond). 2017 Nov 13;131(22):2745-2752. doi: 10.1042/CS20171265. Print 2017 Nov 15.

    PubMed 29021222

  • Iliff JJ, Wang M, Zeppenfeld DM, Venkataraman A, Plog BA, Liao Y, Deane R, Nedergaard M. Cerebral arterial pulsation drives paravascular CSF-interstitial fluid exchange in the murine brain. J Neurosci. 2013 Nov 13;33(46):18190-9. doi: 10.1523/JNEUROSCI.1592-13.2013.

    PubMed 24227727

  • Manava P, Eckrich C, Luciani F, Schmidbauer J, Lell MM, Detmar K. Glymphatic System in Ocular Diseases: Evaluation of MRI Findings. AJNR Am J Neuroradiol. 2022 Jul;43(7):1012-1017. doi: 10.3174/ajnr.A7552. Epub 2022 Jun 30.

    PubMed 35772805

Questions about this trial

What is this clinical trial studying?

An observational study of Glymphatic System, run by Paracelsus Medical University at 1 site in Germany.

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 22 Nov 2023. 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 Germany. 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?

Change of Signal-Intensity (SI)-Measurements with ROI in 3 specific MRI Scans (time frame: Baseline (nativ scan), 20 minutes and 120 minutes after contrast media application). 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 NCT05035251, which also lists 10 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 22 Nov 2023.

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