Clinical trial NCT06183788: Antibody-mediated NMDA Receptor Encephalitis: Symptoms, Biomarkers, and Mechanisms of the Prolonged Recovery Stage
Official title: Antibody-mediated NMDA Receptor Encephalitis: Symptoms, Biomarkers, and Mechanisms of the Prolonged Recovery Stage
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Anti-NMDA Receptor Encephalitis
Keywords: Cognitive Impairment
Encephalitis
Autoimmune
Cognitive rehabilitation
Lead sponsor: Fundacion Clinic per a la Recerca Biomédica
Sponsor class: OTHER
Collaborators: name: Hospital Sant Joan de Deu
First posted: 2023-12-28
Enrollment: 20
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: The encephalitis mediated by antibodies against the NMDA receptor (NMDARe) predominantly affects young adults and children resulting in severe neurologic and psychiatric deficits. After overcoming the acute stage, patients are left with long-lasting behavioral, cognitive, and psychiatric alterations with important socio-family-economical implications. Here investigators postulate that a better knowledge of this stage will improve treatment decisions and outcome.

In Aim 1, the post-acute stage will be clinically characterized, tools to remotely follow cognitive, behavioral and psychiatric deficits will be provided, and the impact of cognitive rehabilitation will be assessed.

In Aim 2, biomarkers (autoimmune, inflammatory, neuronal injury) will be identified as signatures of the acute and post-acute stages.

In Aim 3, a mouse model of NMDARe will be used to determine the underlying mechanisms and treatment of the postacute stage.


Eligibility criteria: Inclusion Criteria:

* Patients ≥12 years old with NMDARe in the post-acute stage of the disease;
* ≤6 months from hospital discharge (acute phase)

Exclusion Criteria (one of the following):

* Inability to obtain informed consent;
* inability to travel to the center.

Primary outcomes:
measure: Age
timeFrame: 18 months
measure: Gender
timeFrame: 18 months
measure: Vision condition
timeFrame: 18 months
measure: Handedness
timeFrame: 18 months
measure: General medical history
timeFrame: 18 months
measure: Allergies
timeFrame: 18 months
measure: Symptoms related to NMDARe
timeFrame: 18 months
measure: Treatments
timeFrame: 18 months
measure: Functional status
timeFrame: 18 months
measure: Intelligence Quotient
timeFrame: 18 months
measure: Verbal working memory
timeFrame: 18 months
measure: Phonological loop
timeFrame: 18 months
measure: Visual working memory
timeFrame: 18 months
measure: Verbal learning
timeFrame: 18 months
measure: Proactive interference verbal memory
timeFrame: 18 months
measure: Short-term verbal memory
timeFrame: 18 months
measure: Long-term verbal memory
timeFrame: 18 months
measure: Verbal recognition memory
timeFrame: 18 months
measure: Verbal discrimination memory
timeFrame: 18 months
measure: Verbal retention memory
timeFrame: 18 months
measure: Immediate visual memory
timeFrame: 18 months
measure: Delayed visual memory
timeFrame: 18 months
measure: Visual retention memory
timeFrame: 18 months
measure: Visual recognition memory
timeFrame: 18 months
measure: Visual discrimination memory
timeFrame: 18 months
measure: Processing speed
timeFrame: 18 months
measure: TMT-A
timeFrame: 18 months
measure: TMT-B
timeFrame: 18 months
measure: Naming
timeFrame: 18 months
measure: Naming with cues
timeFrame: 18 months
measure: Latency in naming
timeFrame: 18 months
measure: Semantic fluency
timeFrame: 18 months
measure: Phonemic fluency
timeFrame: 18 months
measure: Visuospatial skills
timeFrame: 18 months
measure: Visuospatial skills - children
timeFrame: 18 months
measure: Stroop test - word subtest
timeFrame: 18 months
measure: Stroop test - color subtest
timeFrame: 18 months
measure: Stroop test - word-color subtest
timeFrame: 18 months
measure: Detectability - CPT3
timeFrame: 18 months
measure: Omissions - CPT3
timeFrame: 18 months
measure: Comissions - CPT3
timeFrame: 18 months
measure: HRT - CPT3
timeFrame: 18 months
measure: HRT-SD - CPT3
timeFrame: 18 months
measure: Variability- CPT3
timeFrame: 18 months
measure: HRT Block Change - CPT3
timeFrame: 18 months
measure: HRT ISI Change - CPT3
timeFrame: 18 months
measure: Prensence of psychiatric symptoms or disorders in presential assessments
timeFrame: 18 months
measure: Sleep microstructure - Total study time
timeFrame: 18 months
measure: Sleep microstructure - Total sleep time
timeFrame: 18 months
measure: Sleep microstructure - Sleep efficiency
timeFrame: 18 months
measure: Sleep microstructure - Time to sleep onset
timeFrame: 18 months
measure: Sleep microstructure - Time in stage N1
timeFrame: 18 months
measure: Sleep microstructure - Time in stage N2
timeFrame: 18 months
measure: Sleep microstructure - Time in stage N3
timeFrame: 18 months
measure: Sleep microstructure - Time in stage R
timeFrame: 18 months
measure: Sleep microstructure - First epoch of N1
timeFrame: 18 months
measure: Sleep microstructure - First epoch of N2
timeFrame: 18 months
measure: Sleep microstructure - First epoch of N3
timeFrame: 18 months
measure: Sleep microstructure - First epoch of REM
timeFrame: 18 months
measure: Sleep microstructure - REM/NREM time ratio
timeFrame: 18 months
measure: Sleep microstructure - Number of arousals
timeFrame: 18 months
measure: Sleep microstructure - Arousal Index
timeFrame: 18 months
measure: Sleep microstructure - Confusional arousals
timeFrame: 18 months
measure: Sleep microstructure - Direct transition from N3 to W
timeFrame: 18 months
measure: Sleep microstructure - Delta arousals
timeFrame: 18 months
measure: Sleep microstructure - Wake after sleep
timeFrame: 18 months
measure: Adherence to cognitive treatment - 6 months
timeFrame: 6 months
measure: Adherence to cognitive treatment - 9 months
timeFrame: 9 months
measure: Adherence to cognitive treatment - 12 months
timeFrame: 12 months
Secondary outcomes:
measure: Immune/inflammatory signaling-target gene expression pathways
timeFrame: 18 months
measure: Neurofilament light chain (NfL) levels in acute stage
timeFrame: 18 months
measure: Neurofilament light chain (NfL) levels in post-acute stage
timeFrame: 18 months
measure: Cell immunophenotyping - proportion of CD4
timeFrame: 18 months
measure: Cell immunophenotyping - proportion of CD8
timeFrame: 18 months
measure: Cell immunophenotyping - proportion of CD8+CD45RA+
timeFrame: 18 months
measure: Cell immunophenotyping - proportion of CD8+CD45RO+
timeFrame: 18 months
measure: Cell immunophenotyping - proportion of iNKT
timeFrame: 18 months
measure: Cell immunophenotyping - proportion of CD19
timeFrame: 18 months
measure: Cell immunophenotyping - proportion of B naive (IgM+IgD+CD27-)
timeFrame: 18 months
measure: Cell immunophenotyping - proportion of B memory (IgD-)
timeFrame: 18 months
measure: Cell immunophenotyping - proportion of regulatory B cells
timeFrame: 18 months
measure: Cell immunophenotyping - proportion of plasmablasts
timeFrame: 18 months
measure: Cell immunophenotyping - proportion of NK cells
timeFrame: 18 months
measure: MRI
timeFrame: 18 months
measure: EEG: normalcy
timeFrame: 18 months
measure: EEG: time awake
timeFrame: 18 months
measure: EEG: time in drowsiness
timeFrame: 18 months
measure: EEG: time asleep
timeFrame: 18 months
measure: EEG: epileptiform activity
timeFrame: 18 months
measure: EEG: seizures
timeFrame: 18 months
measure: EEG: slowing
timeFrame: 18 months
measure: EEG: Changes with Intermittent Light Stimulation
timeFrame: 18 months
measure: EEG: Changes with hyperventilation
timeFrame: 18 months
measure: Verbal working memory - remote assessment
timeFrame: 18 months
measure: Verbal learning - remote assessment
timeFrame: 18 months
measure: Proactive interference verbal memory - remote assessment
timeFrame: 18 months
measure: Short-term verbal memory - remote assessment
timeFrame: 18 months
measure: Long-term verbal memory - remote assessment
timeFrame: 18 months
measure: Verbal recognition memory - remote assessment
timeFrame: 18 months
measure: Verbal discrimination memory - remote assessment
timeFrame: 18 months
measure: Complex figure copy - remote assessment
timeFrame: 18 months
measure: Time - Complex figure copy - remote assessment
timeFrame: 18 months
measure: Type - Complex figure copy - remote assessment
timeFrame: 18 months
measure: Short-term visual memory - remote assessment
timeFrame: 18 months
measure: Long-term visual memory - remote assessment
timeFrame: 18 months
measure: Orientation in time - remote assessment
timeFrame: 18 months
measure: Orientation in space - remote assessment
timeFrame: 18 months
measure: 5DT Lecture - remote assessment
timeFrame: 18 months
measure: 5DT counting - remote assessment
timeFrame: 18 months
measure: 5DT Choosing - remote assessment
timeFrame: 18 months
measure: 5DT Switching - remote assessment
timeFrame: 18 months
measure: 5DT Inhibition - remote assessment
timeFrame: 18 months
measure: 5DT Flexibility - remote assessment
timeFrame: 18 months
measure: IEDEEDS - remote assessment
timeFrame: 18 months
measure: IEDYERTA - remote assessment
timeFrame: 18 months
measure: IEDYCOST - remote assessment
timeFrame: 18 months
measure: SWM Total Errors - remote assessment
timeFrame: 18 months
measure: SWM Between Errors - remote assessment
timeFrame: 18 months
measure: SWM Within Errors - remote assessment
timeFrame: 18 months
measure: SWM Double Errors - remote assessment
timeFrame: 18 months
measure: SWMS - remote assessment
timeFrame: 18 months
measure: SWMSX - remote assessment
timeFrame: 18 months
measure: SWMPR - remote assessment
timeFrame: 18 months
measure: ERTTH - remote assessment
timeFrame: 18 months
measure: ERTTHH - remote assessment
timeFrame: 18 months
measure: ERTTHS - remote assessment
timeFrame: 18 months
measure: ERTTHF - remote assessment
timeFrame: 18 months
measure: ERTTHA - remote assessment
timeFrame: 18 months
measure: ERTTHSU - remote assessment
timeFrame: 18 months
measure: ERTTHD - remote assessment
timeFrame: 18 months
measure: ERTTFAH - remote assessment
timeFrame: 18 months
measure: ERTTFAS - remote assessment
timeFrame: 18 months
measure: ERTTFAF - remote assessment
timeFrame: 18 months
measure: ERTTFAA - remote assessment
timeFrame: 18 months
measure: ERTTFASU - remote assessment
timeFrame: 18 months
measure: ERTTFAD - remote assessment
timeFrame: 18 months
measure: ERTUHRH - remote assessment
timeFrame: 18 months
measure: ERTUHRS - remote assessment
timeFrame: 18 months
measure: ERTUHRF - remote assessment
timeFrame: 18 months
measure: ERTUHRA - remote assessment
timeFrame: 18 months
measure: ERTUHRSU - remote assessment
timeFrame: 18 months
measure: ERTUHRSD - remote assessment
timeFrame: 18 months
measure: Semantic fluency - remote assessment
timeFrame: 18 months
measure: Phonemic fluency - remote assessment
timeFrame: 18 months
measure: Naming - remote assessment
timeFrame: 18 months
measure: Naming with cues - remote assessment
timeFrame: 18 months
measure: Time in Naming - remote assessment
timeFrame: 18 months
measure: Visuospatial skills - remote assessment
timeFrame: 18 months
measure: Psychiatric symptoms/disorders in remote assessments
timeFrame: 18 months
measure: Serial bias in working memory
timeFrame: 18 months
measure: EEG reactivations in working memory
timeFrame: 18 months
measure: Slow-wave rate of growth during slow-wave sleep period
timeFrame: 18 months
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
state: Cataluña
Study officials:
affiliation: Hospital Clínic
name: Josep Dalmau, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Titulaer MJ, McCracken L, Gabilondo I, Armangue T, Glaser C, Iizuka T, Honig LS, Benseler SM, Kawachi I, Martinez-Hernandez E, Aguilar E, Gresa-Arribas N, Ryan-Florance N, Torrents A, Saiz A, Rosenfeld MR, Balice-Gordon R, Graus F, Dalmau J. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol. 2013 Feb;12(2):157-65. doi: 10.1016/S1474-4422(12)70310-1. Epub 2013 Jan 3.
citation: Arino H, Munoz-Lopetegi A, Martinez-Hernandez E, Armangue T, Rosa-Justicia M, Escudero D, Matos N, Graus F, Sugranyes G, Castro-Fornieles J, Compte A, Dalmau J, Santamaria J. Sleep disorders in anti-NMDAR encephalitis. Neurology. 2020 Aug 11;95(6):e671-e684. doi: 10.1212/WNL.0000000000009987. Epub 2020 Jun 23.
citation: Finke C, Kopp UA, Scheel M, Pech LM, Soemmer C, Schlichting J, Leypoldt F, Brandt AU, Wuerfel J, Probst C, Ploner CJ, Pruss H, Paul F. Functional and structural brain changes in anti-N-methyl-D-aspartate receptor encephalitis. Ann Neurol. 2013 Aug;74(2):284-96. doi: 10.1002/ana.23932. Epub 2013 Jul 8.
citation: Heine J, Kopp UA, Klag J, Ploner CJ, Pruss H, Finke C. Long-Term Cognitive Outcome in Anti-N-Methyl-D-Aspartate Receptor Encephalitis. Ann Neurol. 2021 Dec;90(6):949-961. doi: 10.1002/ana.26241. Epub 2021 Oct 21.
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