NCT05280600

Brief Summary

Autoimmune encephalitis is brain inflammation caused by the immune system mistakenly reacting against proteins in the brain. The commonest form is called NMDAR-antibody encephalitis (N-methyl-D-aspartate receptor antibody encephalitis), a rare condition which mainly affects children and young people and causes difficulties in memory, thinking and mental health which can have significant long-term impacts on education, employment and quality of life. In this project we will use advanced magnetic resonance imaging (MRI) to measure changes in the structure, function and chemistry of the brains of children and young people who are in early recovery from NMDAR-antibody encephalitis and other forms of immune-mediated encephalitis. We will investigate if MRI measurements in patients differ from those in healthy people, and if they can help predict patient outcome one year later, assessed by tests of memory, thinking, mental health and functioning in daily life.

Trial Health

57
Monitor

Trial Health Score

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

Trial has exceeded expected completion date
Enrollment
75

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started May 2022

Typical duration for all trials

Geographic Reach
1 country

1 active site

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

First Submitted

Initial submission to the registry

February 10, 2022

Completed
1 month until next milestone

First Posted

Study publicly available on registry

March 15, 2022

Completed
2 months until next milestone

Study Start

First participant enrolled

May 19, 2022

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 28, 2024

Completed
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 28, 2026

Completed
Last Updated

October 6, 2023

Status Verified

October 1, 2023

Enrollment Period

1.8 years

First QC Date

February 10, 2022

Last Update Submit

October 5, 2023

Conditions

Keywords

Magnetic resonance imaging (MRI)Magnetic resonance spectroscopy (MRS)Resting-state functional MRICognitionUltra-high field MRI

Outcome Measures

Primary Outcomes (3)

  • Cerebral concentrations of GABA and glutamate at the prefrontal cortex and left medial temporal lobe

    Measured with MR spectroscopy - stimulated echo acquisition mode (STEAM) sequence

    Baseline

  • Structural MRI

    Quantitative MRI parameter maps including measurement of median T2 values in the hippocampus

    Baseline

  • Resting-state fMRI

    Whole-brain mapping of the default mode network and seed-based analysis of hippocampal-frontal connectivity

    Baseline

Secondary Outcomes (16)

  • Wechsler Abbreviated Scale of Intelligence 2nd Edition (WASI-II)

    Baseline (all groups), 1 year (patients)

  • Rey Auditory Verbal Learning Test (RAVLT)

    Baseline (all groups), 1 year (patients)

  • Doors & People Test

    Baseline (all groups), 1 year (patients)

  • CANTAB (Cambridge Cognition, UK): Paired Associates Learning

    Baseline (all groups), 1 year (patients)

  • CANTAB (Cambridge Cognition, UK): Rapid Visual Information Processing

    Baseline (all groups), 1 year (patients)

  • +11 more secondary outcomes

Study Arms (3)

NMDAR-antibody encephalitis

Children and young people (ages 8-24 years) with a diagnosis of NMDAR-antibody encephalitis.

Other: Not applicable - non-interventional study

Antibody-negative autoimmune encephalitis

Children and young people (ages 8-24 years) with a diagnosis of autoantibody-negative but probable autoimmune encephalitis or definite autoimmune limbic encephalitis.

Other: Not applicable - non-interventional study

Healthy control

Healthy children and young people (ages 8-24 years).

Other: Not applicable - non-interventional study

Interventions

Not applicable - non-interventional study

Antibody-negative autoimmune encephalitisHealthy controlNMDAR-antibody encephalitis

Eligibility Criteria

Age8 Years - 24 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64)
Sampling MethodNon-Probability Sample
Study Population

All participants will be recruited in the United Kingdom. NMDAR-antibody encephalitis and antibody-negative autoimmune encephalitis groups: Identified by neurologists/paediatric neurologists in secondary/tertiary healthcare settings, or by self-referral via the Encephalitis Society. Healthy control group: Identified from King's College London volunteer databases, friends and siblings of autoimmune encephalitis cases, or recruited from local schools and colleges.

You may qualify if:

  • NMDAR-antibody encephalitis group:
  • Age 8-24 years at study enrollment.
  • Disease onset in the last 12 months before study enrollment.
  • Meets consensus diagnostic criteria (Graus et al., 2016) for either probable anti-NMDAR encephalitis OR definite anti-NMDAR encephalitis.
  • Antibody-negative autoimmune encephalitis group:
  • Age 8-24 years at study enrollment.
  • Disease onset in the last 12 months before study enrollment.
  • Meets consensus diagnostic criteria (Graus et al., 2016) for either autoantibody-negative but probable autoimmune encephalitis OR definite autoimmune limbic encephalitis.
  • Healthy control group:
  • \. Age 8-24 years at study enrollment.

You may not qualify if:

  • All participants:
  • \. Any clear contra-indication for an MRI scan. In particular this would be due to the presence of any implanted devices or metal from previous surgery or accident.
  • Healthy control group:
  • \. A known neurological or neurodevelopmental disorder.
  • NMDAR-antibody encephalitis and antibody-negative autoimmune encephalitis groups:
  • Severe movement disorder/uncontrolled epilepsy/dysautonomia.
  • Previous infective encephalitis with major destructive brain lesions.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Guy's and St Thomas' NHS Foundation Trust

London, Greater London, SE1 7EH, United Kingdom

RECRUITING

Related Publications (1)

  • Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, Cortese I, Dale RC, Gelfand JM, Geschwind M, Glaser CA, Honnorat J, Hoftberger R, Iizuka T, Irani SR, Lancaster E, Leypoldt F, Pruss H, Rae-Grant A, Reindl M, Rosenfeld MR, Rostasy K, Saiz A, Venkatesan A, Vincent A, Wandinger KP, Waters P, Dalmau J. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016 Apr;15(4):391-404. doi: 10.1016/S1474-4422(15)00401-9. Epub 2016 Feb 20.

    PMID: 26906964BACKGROUND

MeSH Terms

Conditions

Anti-N-Methyl-D-Aspartate Receptor EncephalitisAutoimmune Diseases of the Nervous System

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous SystemNervous System NeoplasmsNeoplasms by SiteNeoplasmsParaneoplastic SyndromesEncephalitisBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesNeurodegenerative DiseasesNeuroinflammatory DiseasesAutoimmune DiseasesImmune System Diseases

Study Officials

  • David W Carmichael, PhD MSci

    King's College London

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Michael R Eyre, MBBS MRes

CONTACT

David W Carmichael, PhD MSci

CONTACT

Study Design

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

Study Record Dates

First Submitted

February 10, 2022

First Posted

March 15, 2022

Study Start

May 19, 2022

Primary Completion

February 28, 2024

Study Completion

February 28, 2026

Last Updated

October 6, 2023

Record last verified: 2023-10

Data Sharing

IPD Sharing
Will share

Consent will be requested from participants to share imaging data and summary clinical and demographic data. Where participants consent, imaging data will be de-identified, removing facial features from the magnetic resonance images and all identifying information will be removed from the image header (the part of the file that describes how the image data was acquired). The resulting data will be shared together with anonymised clinical data at the request of other researchers.

Time Frame
To be confirmed
Access Criteria
Requests for data access from researchers at accredited research institutions will be considered. Any requests for data sharing may require a formal agreement to be put in place between the Sponsors and the recipient.

Locations