NAIF 2.0 - COGNIFY

NCT07824297 | Recruiting

• 2 other identifiers: PR(AG)181/2024ERP-2025-14067
• Study Type: observational
• Target: 20
• Locations: 3 countries
• Sites: 3

Brief Summary

The goal of this observational study is to learn whether intracranial dural arteriovenous fistulae, abnormal connections between arteries and veins in the covering of the brain, may affect a brain's waste-clearance system, known as the glymphatic system. The main question it aims to answer is: "Does glymphatic system function change after routine endovascular embolization of an intracranial dural arteriovenous fistula?" Participants who are already scheduled to receive endovascular embolization as part of their regular medical care will undergo advanced brain MRI before treatment and again about 6 months after treatment. Researchers will compare the MRI findings before and after embolization to explore whether treatment is associated with changes in glymphatic-related brain imaging markers.

Conditions

Glymphatic System; Dural Arteriovenous Fistula

Keywords

MRI; DTI; Glymphatic System; Dural Arteriovenous Fistula

Outcome Measures

Primary Outcomes (3)

• Mean DTI-ALPS Index at Baseline and 6 Months After Endovascular Embolization

  The diffusion tensor imaging-analysis along the perivascular space (DTI-ALPS) index will be calculated from directional diffusivities measured in prespecified projection- and association-fiber regions of interest (ROIs). The regional measurements will be combined according to the prespecified DTI-ALPS calculation to obtain one DTI-ALPS index per participant at each time point. DTI-ALPS values will be summarized as the mean and standard deviation at baseline and follow-up. Baseline and follow-up values will be compared within participants using a two-sided paired-samples t-test. A Wilcoxon signed-rank test will be performed as a sensitivity analysis if marked departures from normality or influential outliers are identified. Lower DTI-ALPS values indicate greater lower diffusivity along the perivascular-space direction, suggestive of a glymphatic system impairment. The DTI-ALPS index is unitless.

  Baseline/pre-treatment MRI and follow-up MRI approximately 6 months after endovascular embolization.

• Mean MK at Baseline and 6 Months After Endovascular Embolization

  Mean Kurtosis (MK) will be derived from multi-shell diffusion MRI. Voxelwise mean kurtosis values within white matter ROIs covering the whole brain will be calculated and summarized as the mean and standard deviation at baseline and follow-up. Baseline and follow-up values will be compared within participants using a two-sided paired-samples t-test. A Wilcoxon signed-rank test will be performed as a sensitivity analysis if marked departures from normality or influential outliers are identified. Higher mean kurtosis values indicate a greater degree of non-Gaussian water diffusion, suggestive of a glymphatic system impairment. MK is unitless.

  Baseline/pre-treatment MRI and follow-up MRI approximately 6 months after endovascular embolization.

• Mean FW at Baseline and 6 Months After Endovascular Embolization

  Free-water (FW) will be estimated from multi-shell diffusion MRI using a free-water imaging model. Voxelwise FW values within white matter ROIs covering the whole brain will be calculated and summarized as the mean and standard deviation at baseline and follow-up. Baseline and follow-up values will be compared within participants using a two-sided paired-samples t-test. A Wilcoxon signed-rank test will be performed as a sensitivity analysis if marked departures from normality or influential outliers are identified. FW is a unitless volume fraction ranging from 0 to 1, with higher values indicating a greater proportion of extracellular free water, suggestive of a glymphatic system impairment.

  Baseline/pre-treatment MRI and follow-up MRI approximately 6 months after endovascular embolization.

Secondary Outcomes (3)

• Spearman Rank Correlation Between Cognard Grade and Baseline DTI-ALPS Index

  Baseline/pre-treatment MRI and follow-up MRI approximately 6 months after endovascular embolization.

• Spearman Rank Correlation Between Cognard Grade and Baseline MK

  Baseline/pre-treatment MRI and follow-up MRI approximately 6 months after endovascular embolization

• Spearman Rank Correlation Between Cognard Grade and Baseline FW

  Baseline/pre-treatment MRI and follow-up MRI approximately 6 months after endovascular embolization.

Other Outcomes (3)

• Mean DTI-ALPS Index According to Prespecified Clinical and Angiographic Characteristic

  Baseline/pre-treatment MRI and follow-up MRI approximately 6 months after endovascular embolization.

• Mean MK According to Prespecified Clinical and Angiographic Characteristics

  Baseline/pre-treatment MRI and follow-up MRI approximately 6 months after endovascular embolization.

• Mean FW According to Prespecified Clinical and Angiographic Characteristics

  Baseline/pre-treatment MRI and follow-up MRI approximately 6 months after endovascular embolization.

Study Arms (1)

dAVF patients

Patients with angiografically confirmed diagnosis of intracranial dAVF, aged 18-99 years, candidate for endovascular will be invited to participate in this study

Diagnostic Test: Brain MRI

Interventions

Brain MRI DIAGNOSTIC_TEST

Participants will undergo a brain MRI on a 3T scanner at baseline assessment and approximately 6 months after endovascular embolization. The MRI protocol includes routinary morphologic sequences (e.g., 3D T1-weighted imaging, T2-weighted FLAIR, susceptibility-weighted imaging), as well as a multi-shell diffusion MRI with multiple b-values and gradient directions. These sequences will be used to assess conventional brain findings and diffusion-derived metrics potentially related to glymphatic function, including DTI-ALPS, DKI-MK and FW imaging. The main otcome of the study is to evaluate changes in these metrics in relation to treatment.

dAVF patients

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with angiographically confirmed diagnosis of unruputred intracranial dAVFs, aged 18-99 years, candidate for endovascular embolization treatment with curative intent.

You may qualify if:

• Participant is willing and able to give informed consent for participation in the study.
• Male or Female, aged 18 to 99 years.
• Angiographically confirmed diagnosis of unruptured intracranial dAVF.
• Candidate for endovascular embolization treatment with curative intent.
• Able to undergo Brain MRI.

You may not qualify if:

• Contraindication to angiographic embolization procedures.
• Acute intracranial haemorrhage secondary to dAVFs rupture and/or venous hypertension.
• Any significant disease or disorder which, in the opinion of the investigator, might influence the participant's ability to participate in the study, other contraindications to MRI such as certain metallic implants.

Sponsors & Collaborators

• Hospital Universitari Vall d'Hebron Research Institute: lead
• University of Bologna: collaborator
• University of Oxford: collaborator
• Oxford University Hospitals NHS Trust: collaborator

Study Sites (3)

Università di Bologna

Bologna, 40127, Italy

NOT YET RECRUITING

Hospital Universitario Vall D'Hebron

Barcelona, 08035, Spain

RECRUITING

University of Oxford

Oxford, OX3 9DU, United Kingdom

NOT YET RECRUITING

Related Publications (3)

• Sacchi L, D'Agata F, Campisi C, Arcaro M, Carandini T, Orzsik B, Dal Maschio VP, Fenoglio C, Pietroboni AM, Ghezzi L, Serpente M, Pintus M, Conte G, Triulzi F, Lopiano L, Galimberti D, Cercignani M, Bozzali M, Arighi A. A "glympse" into neurodegeneration: Diffusion MRI and cerebrospinal fluid aquaporin-4 for the assessment of glymphatic system in Alzheimer's disease and other dementias. Hum Brain Mapp. 2024 Aug 15;45(12):e26805. doi: 10.1002/hbm.26805.

  PMID: 39185685 RESULT

• Taoka T, Masutani Y, Kawai H, Nakane T, Matsuoka K, Yasuno F, Kishimoto T, Naganawa S. Evaluation of glymphatic system activity with the diffusion MR technique: diffusion tensor image analysis along the perivascular space (DTI-ALPS) in Alzheimer's disease cases. Jpn J Radiol. 2017 Apr;35(4):172-178. doi: 10.1007/s11604-017-0617-z. Epub 2017 Feb 14.

  PMID: 28197821 RESULT

• Gramegna LL, Ortega G, Dinia L, Aixut S, Rosati S, Vega P, Luttich A, Remollo S, Gonzalez A, Murias E, Chirife Chaparro O, Moreu M, Requena M, de Dios Lascuevas M, Hernandez D, Quintana M, Puig J, Rovira A, Tomasello A. Cognitive improvement following endovascular embolization in patients with intracranial dural arteriovenous fistula: The Neuropsychology in dural ArterIal Fistula (NAIF) Study. J Neurointerv Surg. 2023 Dec 7:jnis-2023-021033. doi: 10.1136/jnis-2023-021033. Online ahead of print.

  PMID: 38071581 RESULT

MeSH Terms

Conditions

Central Nervous System Vascular Malformations

Condition Hierarchy (Ancestors)

Nervous System Malformations; Nervous System Diseases; Vascular Malformations; Cardiovascular Abnormalities; Cardiovascular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Central Study Contacts

Laura Ludovica Gramegna, MD, PhD

CONTACT

+34934893000; laura.gramegna@vhir.org

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2026
• First Posted: September 17, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2029
• Last Updated: September 17, 2026

Record last verified: 2026-09

Locations

ES (1); GB (1); IT (1)