NCT06321588

Brief Summary

The goal of this observational study is to investigate the frequency and the possible pathogenic role of neuronal synaptic antibodies (NSAb) in patients with cognitive impairment (CI). The main questions it aims to answer are:

  1. 1.the frequency and associated features of NSAb in patients with CI and the usefulness of a clinical score in improving autoimmune dementia (AID) diagnosis;
  2. 2.the clinical significance of NSAb in patients with CI not fulfilling the autoimmune encephalitis (AE) criteria and serum NSAb (NSAb-pos-CI);
  3. 3.the impact of blood-brain-barrier (BBB) dysfunction on their pathogenicity.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
300

participants targeted

Target at P75+ for all trials

Timeline
2mo left

Started May 2023

Typical duration for all trials

Geographic Reach
1 country

3 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress95%
May 2023Jun 2026

Study Start

First participant enrolled

May 10, 2023

Completed
10 months until next milestone

First Submitted

Initial submission to the registry

March 14, 2024

Completed
6 days until next milestone

First Posted

Study publicly available on registry

March 20, 2024

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2026

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2026

Last Updated

February 11, 2026

Status Verified

July 1, 2025

Enrollment Period

3.1 years

First QC Date

March 14, 2024

Last Update Submit

February 9, 2026

Conditions

Cognitive ImpairmentDementia

Outcome Measures

Primary Outcomes (3)

  • frequency of antibodies against neuronal antigens

    NSAb frequency will be calculated by dividing the number of patients with NSAb with the total number of patients

    at baseline

  • frequency of antibodies against neuronal antigens

    NSAb frequency will be calculated by dividing the number of patients with NSAb with the total number of patients

    12 months (54 weeks)

  • creation of a score that predicts the presence of NSAb

    Based on logistic regression models including the clinical, imaging and biomarkers data. The minimum and maximum score is to be defined on the bases of the analyses of the clinical data at 24 months milestone.An higher score is expected to be associated with the antibody presence.

    24 months (108 weeks)

Secondary Outcomes (8)

  • changes of neurodegeneration biomarkers

    at baseline

  • changes of neurodegeneration biomarkers

    1 year (54 weeks)

  • changes of neuroanatomy

    at baseline

  • changes of neuroanatomy

    1 year (54 weeks)

  • changes of inflammatory biomarkers

    at baseline

  • +3 more secondary outcomes

Study Arms (2)

retrospective cohort

patients with a diagnosis of new-onset neurocognitive disorders (major and minor) with onset within the previous 24 months

prospective cohort

patients with a diagnosis of new-onset neurocognitive disorders (major and minor) with onset within the previous 24 months

Eligibility Criteria

Age40 Years - 90 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

patients with a diagnosis of new-onset neurocognitive disorders (major and minor)

You may qualify if:

  • both sexes
  • adult (aged between 40 and 90 years)
  • patients with a diagnosis of new-onset neurocognitive disorders (major and minor), as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, with onset within the previous 24 months

You may not qualify if:

  • \- presence of a history of seizures within 4 weeks from onset.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

IRCCS Istituto delle Scienze Neurologiche di Bologna

Bologna, Bologna, 40139, Italy

RECRUITING

Istituto Auxologico Italiano IRCCS

Milan, Milano, 20095, Italy

RECRUITING

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, Milano, 20133, Italy

RECRUITING

Related Publications (12)

  • Bartels F, Stronisch T, Farmer K, Rentzsch K, Kiecker F, Finke C. Neuronal autoantibodies associated with cognitive impairment in melanoma patients. Ann Oncol. 2019 May 1;30(5):823-829. doi: 10.1093/annonc/mdz083.

    PMID: 30840061RESULT

  • Brunkhorst R, Pfeilschifter W, Foerch C. Astroglial proteins as diagnostic markers of acute intracerebral hemorrhage-pathophysiological background and clinical findings. Transl Stroke Res. 2010 Dec;1(4):246-51. doi: 10.1007/s12975-010-0040-6. Epub 2010 Aug 28.

    PMID: 24323552RESULT

  • Castillo-Gomez E, Oliveira B, Tapken D, Bertrand S, Klein-Schmidt C, Pan H, Zafeiriou P, Steiner J, Jurek B, Trippe R, Pruss H, Zimmermann WH, Bertrand D, Ehrenreich H, Hollmann M. All naturally occurring autoantibodies against the NMDA receptor subunit NR1 have pathogenic potential irrespective of epitope and immunoglobulin class. Mol Psychiatry. 2017 Dec;22(12):1776-1784. doi: 10.1038/mp.2016.125. Epub 2016 Aug 9.

    PMID: 27502473RESULT

  • Constantinescu R, Krysl D, Bergquist F, Andren K, Malmestrom C, Asztely F, Axelsson M, Menachem EB, Blennow K, Rosengren L, Zetterberg H. Cerebrospinal fluid markers of neuronal and glial cell damage to monitor disease activity and predict long-term outcome in patients with autoimmune encephalitis. Eur J Neurol. 2016 Apr;23(4):796-806. doi: 10.1111/ene.12942. Epub 2016 Jan 29.

    PMID: 26822123RESULT

  • Dubey D, Kothapalli N, McKeon A, Flanagan EP, Lennon VA, Klein CJ, Britton JW, So E, Boeve BF, Tillema JM, Sadjadi R, Pittock SJ. Predictors of neural-specific autoantibodies and immunotherapy response in patients with cognitive dysfunction. J Neuroimmunol. 2018 Oct 15;323:62-72. doi: 10.1016/j.jneuroim.2018.07.009. Epub 2018 Jul 25.

    PMID: 30196836RESULT

  • Dubois B, Villain N, Frisoni GB, Rabinovici GD, Sabbagh M, Cappa S, Bejanin A, Bombois S, Epelbaum S, Teichmann M, Habert MO, Nordberg A, Blennow K, Galasko D, Stern Y, Rowe CC, Salloway S, Schneider LS, Cummings JL, Feldman HH. Clinical diagnosis of Alzheimer's disease: recommendations of the International Working Group. Lancet Neurol. 2021 Jun;20(6):484-496. doi: 10.1016/S1474-4422(21)00066-1. Epub 2021 Apr 29.

    PMID: 33933186RESULT

  • Flanagan EP, McKeon A, Lennon VA, Boeve BF, Trenerry MR, Tan KM, Drubach DA, Josephs KA, Britton JW, Mandrekar JN, Lowe V, Parisi JE, Pittock SJ. Autoimmune dementia: clinical course and predictors of immunotherapy response. Mayo Clin Proc. 2010 Oct;85(10):881-97. doi: 10.4065/mcp.2010.0326.

    PMID: 20884824RESULT

  • Giannoccaro MP, Cossins J, Sorland K, Fluge O, Vincent A. Searching for Serum Antibodies to Neuronal Proteins in Patients With Myalgic Encephalopathy/Chronic Fatigue Syndrome. Clin Ther. 2019 May;41(5):836-847. doi: 10.1016/j.clinthera.2019.04.001. Epub 2019 May 1.

    PMID: 31053295RESULT

  • Gibson LL, McKeever A, Cullen AE, Nicholson TR, Aarsland D, Zandi MS, Pollak TA. Neuronal surface autoantibodies in dementia: a systematic review and meta-analysis. J Neurol. 2021 Aug;268(8):2769-2779. doi: 10.1007/s00415-020-09825-0. Epub 2020 Apr 18.

    PMID: 32306172RESULT

  • Pollak TA, Vincent A, Iyegbe C, Coutinho E, Jacobson L, Rujescu D, Stone J, Jezequel J, Rogemond V, Jamain S, Groc L, David A, Egerton A, Kahn RS, Honnorat J, Dazzan P, Leboyer M, McGuire P. Relationship Between Serum NMDA Receptor Antibodies and Response to Antipsychotic Treatment in First-Episode Psychosis. Biol Psychiatry. 2021 Jul 1;90(1):9-15. doi: 10.1016/j.biopsych.2020.11.014. Epub 2020 Nov 24.

    PMID: 33536130RESULT

  • Wagner J, Witt JA, Helmstaedter C, Malter MP, Weber B, Elger CE. Automated volumetry of the mesiotemporal structures in antibody-associated limbic encephalitis. J Neurol Neurosurg Psychiatry. 2015 Jul;86(7):735-42. doi: 10.1136/jnnp-2014-307875. Epub 2014 Sep 2.

    PMID: 25185210RESULT

  • Yeshokumar AK, Gordon-Lipkin E, Arenivas A, Cohen J, Venkatesan A, Saylor D, Probasco JC. Neurobehavioral outcomes in autoimmune encephalitis. J Neuroimmunol. 2017 Nov 15;312:8-14. doi: 10.1016/j.jneuroim.2017.08.010. Epub 2017 Aug 31.

    PMID: 28889962RESULT

MeSH Terms

Conditions

Cognitive DysfunctionDementia

Condition Hierarchy (Ancestors)

Cognition DisordersNeurocognitive DisordersMental DisordersBrain DiseasesCentral Nervous System DiseasesNervous System Diseases

Study Officials

  • Maria Pia Giannoccaro, Dr.

    IRCCS Istituto delle Scienze Neurologiche di Bologna

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Maria Pia Giannoccaro, Dr.

CONTACT

+390514966112mariapia.giannoccaro@ausl.bologna.it

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
OTHER
Sponsor Type
OTHER GOV
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 14, 2024

First Posted

March 20, 2024

Study Start

May 10, 2023

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

June 30, 2026

Last Updated

February 11, 2026

Record last verified: 2025-07

Locations

IT(3)