AzTrials
AzTrials

Limbic Encephalitis With LGI1 AntibodiesNCT06515106

Antibody-mediated LGI1 Encephalitis: Symptoms, Biomarkers, and Mechanisms of the Chronic Phase of the Disease

A study testing Remote cognitive rehabilitation program in people with Limbic Encephalitis With LGI1 Antibodies, run by Fundacion Clinic per a la Recerca Biomédica at 1 site in Spain.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

The encephalitis mediated by antibodies against Leucine-rich, glioma inactivated 1 protein (anti-LGI1 encephalitis) predominantly affects men (M:F, 6:4) and mostly older than 60 years. Read more about this study

Who is it for?
Any age
Conditions the study is for
Limbic Encephalitis With LGI1 Antibodies
What is being tested?
Remote cognitive rehabilitation program
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteSpain
Study dates
18 Dec 2023to 31 Dec 2026
Phase
Interventional
Are there results?
Not yet: the study is under way

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 Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Patients with Antibody-mediated LGI-1 encephalitis in the post-acute stage of the disease;
  • Patients has been discharged from hospital (acute phase).

Who cannot join

  • Inability to obtain informed consent;
  • Inability to travel to the center.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Josep Dalmau, MD,PhD contact

34 93 227 1738

jdalmau@clinic.cat

Spain1 site, 1 recruiting

  • Hospital Clínic de Barcelona

    Barcelona, Catalonia, 08036

    Josep Dalmau, MD, PhD, +34 93 227 1738, jdalmau@clinic.cat

    Victor Patricio, MS, +34 93 227 1738, vpatricio@recerca.clinic.cat

    Recruiting

Other trials in Spain

About this study

The encephalitis mediated by antibodies against Leucine-rich, glioma inactivated 1 protein (anti-LGI1 encephalitis) predominantly affects men (M:F, 6:4) and mostly older than 60 years. The disease has two distinct clinical phases: The acute phase in which the majority of patients develop severe short-term memory deficits (unable to remember events or experiences that occurred a few minutes earlier). This memory impairment can be preceded or accompanied by one or more of the following: hyponatremia (60% of patients), a highly distinctive type of seizures called facio-brachial dystonic seizures (~40% of patients), along with confusion, irritability and other types of focal seizures or less frequently, generalized seizures. In addition, many patients at this stage have symptoms of REM sleep behavior disorder. In this stage, the CSF may show pleocytosis or mild increase of proteins, the EEG is usually abnormal, and in ~60% of the patients the MRI shows typical increased FLAIR signal in medial temporal lobes (11). There is a clinical sub-phenotype (~13% of patients) in which the disease presents as a rapidly progressive cognitive decline without the indicated FLAIR MRI changes. About 70% of patients improve rapidly with corticosteroids and immunotherapy (eg, intravenous immunoglobulins and/or plasma exchange), but the improvement is often partial. After the acute phase, there is a chronic or residual phase which represents the interval from improvement of initial symptoms until the disease is considered no longer active and the remaining symptoms are thought to be irreversible. This chronic phase may take several months (it has been less well studied), and is characterized by the absence of CSF pleocytosis and inflammatory MRI changes (albeit this may show residual hippocampal atrophy), and very low or undetectable titers of serum antibodies. Most patients are unable to return to their job or previous activities due to residual (irreversible) memory or cognitive deficits accompanied by signs of moderate brain atrophy. In addition, we and others have shown that about 27-35% of patients have relapsing symptoms after improving from the acute phase (. Although acute symptomatic seizures (facio-brachial dystonic and others) occur in ~90% of patients during the acute phase of the disease, less than 10% of patients develop chronic epilepsy often associated with hippocampal sclerosis. Therefore, the prevailing concept on this disease suggests a syndrome and clinical course in which the acute phase shows rapid, albeit partial, response to immunotherapy, and the symptoms of the chronic phase represent a burnout or irreversible process, in which the disease is no longer active, and the potential improvement of remaining symptoms is uncertain.

Here investigators postulate that a better knowledge of this stage will improve treatment decisions and outcome.

Read more

In Aim 1, the post-acute stage will be clinically characterized.

In Aim 2, the impact of cognitive rehabilitation will be assessed.

In Aim 3, a mouse model of anti-LGI1 encephalitis will be used to determine the underlying mechanisms and treatment of the postacute stage.

Being tested
Remote cognitive rehabilitation program
Keywords
Cognitive Impairment, Encephalitis, Autoimmune, Cognitive rehabilitation
Medical subject headings
Cognitive Dysfunction, Encephalitis

What participants receive

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

  • Remote cognitive rehabilitation programBehavioural

    Behavioral: Remote cognitive rehabilitation program Remote cognitive rehabilitation program will be performed through an online validated platform (Guttmann NeuroPersonalTrainer: https://gnpt.es/) run by the psychologists team. This is a Sanitary Product with CE certification (Sanitary Product RPS/430/2014; International Patent [PCT/ES2008/00677]) and here will be used within its approved indications. The rehabilitation program will increase in difficulty and decrease in frequency during the first year of follow-up (V1-V3).

Study groups in NCT06515106
Study groupRoleWhat they receive
Antibody-mediated LGI1 encephalitis patientsExperimentalParticipants of a prospective cohort in post-acute phase of the Antibody-mediated NMDA Receptor Encephalitis that will received a behavioral treatment.
Receives: Behavioral: Remote cognitive rehabilitation program

What is being measured

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

  1. Age

    Age measured in years

    Measured: 12 months

  2. Gender

    Male or female

    Measured: 12 months

  3. Handedness

    Right- or Left-handed

    Measured: 12 months

  4. General medical history

    Description of the most important issues compiled in the general medical history of the participant

    Measured: 12 months

  5. Allergies

    List of allergies of each participant

    Measured: 12 months

  6. Symptoms related to anti-LGI1 encephalitis

    Detailed description of symptoms experienced before, during and after the post-acute phase of anti-LGI1 encephalitis.

    Measured: 12 months

  7. Treatments

    All treatments in which the participant is being involved.

    Measured: 12 months

  8. Functional status

    Functional status according to Modified Rankin Scale (mRS).

    Modified Rankin Scale:

    • Range: from 0 points (no symptoms) to 6 points (dead).

    Measured: 12 months

  9. Intelligence Quotient

    Estimated through General Ability Index (GAI; from Weschler Adult Intelligence Scale - IV (WAIS-IV).

    This index is obtained through Verbal Comprehension Index (VCI) and Perceptual Reasoning Index (PRI).

    Range of GAI: from 40 to 160. Higher is better. Range of VCI: from 50 to 150. Higher is better. Range of PRI: from 50 to 150. Higher is better.

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  10. Verbal working memory

    Verbal Working Memory: Working Memory Index (WMI) from WAIS-IV.

    • Range of WMI: from 50 to 150. Higher is better.

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  11. Phonological loop

    Assessed by Forward order span of Digit span subtest from WAIS-IV.

    • Range: from 0 to 9

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  12. Visual working memory

    Visual Working Memory: Spatial location subtest from Weschler Memory Scale - IV (WMS-IV).

    • Range of Spatial Location subtest: from 0 to 32. Higher is better.

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  13. Verbal learning

    Assessed by:

    Adults: España - Complutense Auditory-Verbal Learning Test (Test de Aprendizaje Verbal España - Complutense; TAVEC

    • Total learning: range: from 0 to 80. Higher is better.

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  14. Proactive interference verbal memory

    Assessed by:

    Adults: España - Complutense Auditory-Verbal Learning Test (Test de Aprendizaje Verbal España - Complutense; TAVEC).

    • Interference list: range: 0 to 15. Higher is better.

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  15. Short-term verbal memory

    Assessed by:

    Adults: España - Complutense Auditory-Verbal Learning Test (Test de Aprendizaje Verbal España - Complutense; TAVEC).

    • Short-term memory free recall: range: 0 to 15. Higher is better.

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  16. Long-term verbal memory

    Assessed by:

    Adults: España - Complutense Auditory-Verbal Learning Test (Test de Aprendizaje Verbal España - Complutense; TAVEC):

    • Long-term memory free recall: range: 0 to 15. Higher is better.

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  17. Verbal recognition memory

    Assessed by:

    Adults: España - Complutense Auditory-Verbal Learning Test (Test de Aprendizaje Verbal España - Complutense; TAVEC).

    • Word-list Recognition: range: 0 to 15. Higher is better.

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  18. Verbal discrimination memory

    Assessed by:

    Adults: España - Complutense Auditory-Verbal Learning Test (Test de Aprendizaje Verbal España - Complutense; TAVEC)

    Discrimination index of word-list: False positives + omissions of recognition between 44 total words to recognize. Higher is better.

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  19. Verbal retention memory

    Assessed by:

    Adults: España - Complutense Auditory-Verbal Learning Test (Test de Aprendizaje Verbal España - Complutense; TAVEC); or Infants: España - Complutense Auditory-Verbal Learning Test for Children (Test de Aprendizaje Verbal España - Complutense Infantil; TAVECI)

    • Retention index: percentatge of Long-term memory free recall between Short-term memory free recall. Higher is better.

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  20. Immediate visual memory

    Assessed by: Brief Visuospatial Memory Test - Revised (BVMT-R)

    • Immediate visual memory: range: from 0 to 36. Higher is better.

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  21. Delayed visual memory

    Assessed by: Brief Visuospatial Memory Test - Revised (BVMT-R)

    • Delayed visual memory: range: from 0 to 12. Higher is better.

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  22. Visual retention memory

    Assessed by: Brief Visuospatial Memory Test - Revised (BVMT-R)

    • Retention index: percentatge of Long-term memory free recall between the Higher punctuation at Trial 2 or 3. Higher is better.

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  23. Visual recognition memory

    Assessed by: Brief Visuospatial Memory Test - Revised (BVMT-R)

    • Figure Recognition: range: from 0 to 6. Higher is better.

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  24. Visual discrimination memory

    Assessed by: Brief Visuospatial Memory Test - Revised (BVMT-R)

    • Discrimination index: figure recognized minus false positives. Range: from -6 to 6. Higher is better.

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  25. Processing speed

    Symbol Search subtest (WAIS-IV)

    • Total (correct answers less incorrect answers): from 0 to 60

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  26. TMT-A

    Trail Making Test part A (TMT-A):

    • Time in seconds: from 0 to infinity.

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  27. Naming

    Assessed by: Boston Naming Test (BNT)

    • Total correct: from 0 to 60

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  28. Naming with cues

    Assessed by: Boston Naming Test (BNT)

    • Total correct with phonemic cue: from 0 to 60

    Measured: 12 months

  29. Latency in naming

    Assessed by: Boston Naming Test (BNT)

    • Time to complete test in seconds

    Measured: 12 months

  30. Semantic fluency

    Number of name of animals recalled in 1 minute: range: from 0 to infinity.

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  31. Phonemic fluency

    Number of words started by letter "M" recalled in 1 minute:

    • Range: from 0 to infinity.

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  32. Visuospatial skills

    Number location subtest of the Visual-Object Spatial and Perceptual battery.

    • Range: from 0 to 10

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  33. Symbolic gesture right hand - order

    Symbolic gesture right hand - order subtest from Test Barcelona - Revised

    • Range: from 0 to 10

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  34. Symbolic gesture left hand - order

    Symbolic gesture left hand - order subtest from Test Barcelona - Revised

    • Range: from 0 to 10

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  35. Symbolic gesture right hand - imitation

    Symbolic gesture right hand - imitation subtest from Test Barcelona

    • Range: from 0 to 10

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  36. Symbolic gesture left hand - imitation

    Symbolic gesture left hand - imitation subtest from Test Barcelona - Revised

    • Range: from 0 to 10

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  37. Bilateral ideomotor praxis - imitation

    Bilateral ideomotor praxis imitation subtest from Test Barcelona

    • Range: from 0 to 10

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  38. Stroop test - word subtest

    • Words: words read in 45 seconds

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  39. Stroop test - color subtest

    • Colour: colours distinguished in 45 seconds.

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  40. Stroop test - word-color subtest

    • Word-colour: colours distinguished in 45 seconds.

    Raw scores were transformed into standard T-scores (mean 50 ± standard deviation [SD] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

    Measured: 12 months

  41. Prensence of psychiatric symptoms or disorders

    Number of participants with psychiatric symptoms/disorders following DSM-IV-TR guidelines (psychotic symptoms, symptoms of depression, symptoms of mania, global functioning).

    Measured: 12 months

  42. Sleep microstructure - Total study time

    It will be adapted to patient's sleep habits (~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported.

    Parameters:

    • Total sleep time: minutes

    Measured: 12 months

  43. Sleep microstructure - Total sleep time

    It will be adapted to patient's sleep habits (~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported.

    Parameters:

    • Total sleep time: minutes

    Measured: 12 months

  44. Sleep microstructure - Sleep efficiency

    It will be adapted to patient's sleep habits (~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported.

    Parameters:

    • Sleep efficiency: based on total study time and total sleep time

    Measured: 12 months

  45. Sleep microstructure - Time to sleep onset

    It will be adapted to patient's sleep habits (~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported.

    Parameters:

    • Time to sleep onset: minutes

    Measured: 12 months

  46. Sleep microstructure - Time in stage N1

    It will be adapted to patient's sleep habits (~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported.

    Parameters:

    • Time in stage N1: minutes

    Measured: 12 months

  47. Sleep microstructure - Time in stage N2

    It will be adapted to patient's sleep habits (~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported.

    Parameters:

    • Time in stage N2: minutes

    Measured: 12 months

  48. Sleep microstructure - Time in stage N3

    It will be adapted to patient's sleep habits (~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported.

    Parameters:

    • Time in stage N3: minutes

    Measured: 12 months

  49. Sleep microstructure - Time in stage R

    It will be adapted to patient's sleep habits (~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported.

    Parameters:

    • Time in stage R: minutes

    Measured: 12 months

  50. Sleep microstructure - First epoch of N1

    It will be adapted to patient's sleep habits (~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported.

    Parameters:

    • First epoch of N1: minutes

    Measured: 12 months

  51. Sleep microstructure - First epoch of N2

    It will be adapted to patient's sleep habits (~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported.

    Parameters:

    • First epoch of N2: minutes

    Measured: 12 months

  52. Sleep microstructure - First epoch of N3

    It will be adapted to patient's sleep habits (~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported.

    Parameters:

    • First epoch of N3: minutes

    Measured: 12 months

  53. Sleep microstructure - First epoch of REM

    It will be adapted to patient's sleep habits (~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported.

    Parameters:

    • First epoch of REM: minutes

    Measured: 12 months

  54. Sleep microstructure - REM/NREM time ratio

    It will be adapted to patient's sleep habits (~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported.

    Parameters:

    • REM/NREM time ratio

    Measured: 12 months

  55. Sleep microstructure - Number of arousals

    It will be adapted to patient's sleep habits (~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported.

    Parameters:

    • Number of arousals (total)

    Measured: 12 months

  56. Sleep microstructure - Arousal Index

    It will be adapted to patient's sleep habits (~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported.

    Parameters:

    • Arousal Index

    Measured: 12 months

  57. Sleep microstructure - Confusional arousals

    It will be adapted to patient's sleep habits (~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported.

    Parameters:

    • Confusional arousals: Yes or No

    Measured: 12 months

  58. Sleep microstructure - Direct transition from N3 to W

    It will be adapted to patient's sleep habits (~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported.

    Parameters:

    • Direct transition from N3 to W: yes or no

    Measured: 12 months

  59. Sleep microstructure - Delta arousals

    It will be adapted to patient's sleep habits (~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported.

    Parameters:

    • Delta arousals: yes, no or unknown

    Measured: 12 months

  60. Sleep microstructure - Wake after sleep

    It will be adapted to patient's sleep habits (~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported.

    Parameters:

    • Wake after sleep: hour

    Measured: 12 months

  61. Adherence to cognitive treatment - 6 months

    Percentage of sessions performed in 6 months out of 48 (sessions performed out of 48 x 100)

    Measured: 6 months

  62. Adherence to cognitive treatment - 9 months

    Percentage of sessions performed in 9 months (sessions performed out of 54 x 100)

    Measured: 9 months

  63. Adherence to cognitive treatment - 12 months

    Percentage of sessions performed in 9 months out of 60 (sessions performed out of 60 x 100)

    Measured: 12 months

  64. Cardiovagal evaluation. (Composite autonomic scoring scale)

    Continuous electrocardiogram heart rate changes during deep breathing and postural changes (beats per minute).Composite autonomic scoring scale minimun 0, maximum 3, higher scores mean a worse outcome.

    Measured: 12 months

  65. Valsava ratio

    Continuous electrocardiogram heart rate changes during Valsalva manoeuvre (ratio).

    Measured: 12 months

  66. Sympathetic evaluation (Composite autonomic scoring scale)

    Beat-to-beat blood pressure changes to isometric exercise, Valsalva manoeuvre and postural changes, (mmHg). Composite autonomic scoring scale minimun 0, maximum 4, higher scores mean a worse outcome

    Measured: 12 months

  67. Composite Autonomic Symptom Score (Compass-31)

    Self-scoring Compass 31 autonomic assessment. Minimum 0, maximum 100, higher scores mean a worse outcome.

    Measured: 12 months

  68. Electromyography (EMG)

    Needle recording electrode will be inserted into different muscles (orbicularis oris, extensor indicis propius, tibialis anterior).Presence of abnormal discharges will be recorded (0 none to 4 maximum).

    Measured: 12 months

  69. Brainstem reflex

    Trigeminal blink reflex, mediated by trigemino-facial ponto-medullary -circuits will be assessed. Surface recording electrodes will be attached over the orbicularis oculi in both sides with active electrode over the middle part of the lower eyelid and the reference at the lateral cantus of the eye . Stimulating electrodes will be placed over the supraorbital nerve. Ipsilateral (R1, R2) and contralateral responses (R2c) latencies measured in ms will be analyzed

    Measured: 12 months

  70. MRI

    It will be conducted on a 3 Tesla Prisma scanner using a 32-channel head coil. Scanning takes ~50 min including 3D T1-weighted in sagittal plane; T2*axial EPI; axial diffusion weighted EPI; 3D sagittal FLAIR; resting state functional MRI and glutamate and H2O univoxel spectroscopy in dorsolateral prefrontal cortex and hippocampus. There is no contrast used for the MRI scans

    Outcome for MRI is normal or abnormal. Investigators will review all MRI sequences and determine if the MRI is abnormal and then describe the abnormality or abnormalities seen.

    Measured: 12 months

  71. EEG: normalcy

    It will include standard clinical EEG protocol (43 channels, 512 Hz18) (primary variables), and EEG reactivations of memories prior to new trials (secondary variables) while participants perform WM tasks, which will be synchronized with the task software in a laptop. The memory content from alpha power across electrodes will be related to the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

    Performances of the subjects produces a reactivation of memory prior to new trials while participants perform working memory tasks, and relate the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

    • Normalcy: yes or no.

    Measured: 12 months

  72. EEG: time awake

    It will include standard clinical EEG protocol (43 channels, 512 Hz18) (primary variables), and EEG reactivations of memories prior to new trials (secondary variables) while participants perform WM tasks, which will be synchronized with the task software in a laptop. The memory content from alpha power across electrodes will be related to the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

    Performances of the subjects produces a reactivation of memory prior to new trials while participants perform working memory tasks, and relate the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

    Parameters:

    • Time awake: percentage

    Measured: 12 months

  73. EEG: time in drowsiness

    It will include standard clinical EEG protocol (43 channels, 512 Hz18) (primary variables), and EEG reactivations of memories prior to new trials (secondary variables) while participants perform WM tasks, which will be synchronized with the task software in a laptop. The memory content from alpha power across electrodes will be related to the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

    Performances of the subjects produces a reactivation of memory prior to new trials while participants perform working memory tasks, and relate the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

    Parameters:

    • Time in drowsiness: percentage

    Measured: 12 months

  74. EEG: time asleep

    It will include standard clinical EEG protocol (43 channels, 512 Hz18) (primary variables), and EEG reactivations of memories prior to new trials (secondary variables) while participants perform WM tasks, which will be synchronized with the task software in a laptop. The memory content from alpha power across electrodes will be related to the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

    Performances of the subjects produces a reactivation of memory prior to new trials while participants perform working memory tasks, and relate the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

    Parameters:

    • Time asleep: percentage

    Measured: 12 months

  75. EEG: epileptiform activity

    It will include standard clinical EEG protocol (43 channels, 512 Hz18) (primary variables), and EEG reactivations of memories prior to new trials (secondary variables) while participants perform WM tasks, which will be synchronized with the task software in a laptop. The memory content from alpha power across electrodes will be related to the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

    Performances of the subjects produces a reactivation of memory prior to new trials while participants perform working memory tasks, and relate the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

    Parameters:

    • Epileptiform activity: yes or no

    Measured: 12 months

  76. EEG: seizures

    It will include standard clinical EEG protocol (43 channels, 512 Hz18) (primary variables), and EEG reactivations of memories prior to new trials (secondary variables) while participants perform WM tasks, which will be synchronized with the task software in a laptop. The memory content from alpha power across electrodes will be related to the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

    Performances of the subjects produces a reactivation of memory prior to new trials while participants perform working memory tasks, and relate the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

    Parameters:

    • Seizures: yes or no

    Measured: 12 months

  77. EEG: slowing

    It will include standard clinical EEG protocol (43 channels, 512 Hz18) (primary variables), and EEG reactivations of memories prior to new trials (secondary variables) while participants perform WM tasks, which will be synchronized with the task software in a laptop. The memory content from alpha power across electrodes will be related to the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

    Performances of the subjects produces a reactivation of memory prior to new trials while participants perform working memory tasks, and relate the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

    Parameters:

    • EEG slowing: yes or no

    Measured: 12 months

  78. EEG: Changes with Intermittent Light Stimulation

    It will include standard clinical EEG protocol (43 channels, 512 Hz18) (primary variables), and EEG reactivations of memories prior to new trials (secondary variables) while participants perform WM tasks, which will be synchronized with the task software in a laptop. The memory content from alpha power across electrodes will be related to the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

    Performances of the subjects produces a reactivation of memory prior to new trials while participants perform working memory tasks, and relate the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

    Parameters:

    • Changes with Intermittent Light Stimulation: yes or no

    Measured: 12 months

  79. EEG: Changes with hyperventilation

    It will include standard clinical EEG protocol (43 channels, 512 Hz18) (primary variables), and EEG reactivations of memories prior to new trials (secondary variables) while participants perform WM tasks, which will be synchronized with the task software in a laptop. The memory content from alpha power across electrodes will be related to the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

    Performances of the subjects produces a reactivation of memory prior to new trials while participants perform working memory tasks, and relate the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

    Parameters:

    • Changes with hyperventilation: yes or no

    Measured: 12 months

Secondary outcomes (4)

  1. LGI-1 antibodies

    Determined with brain tissue immunohistochemistry and cell - based assays

    Measured: 12 months

  2. HLA genotyping

    performed by standard techniques based on DNA - PCR and polymorphism identification by reverse hybridization with specific probes and fluorescence labelling of hybridized fragments (PCR - SSOP) (Immucor GTI Diagnostics Inc.Waukesha USA) in combination with genomic DNA sequencing by Sanger methodology (PCRSBT).

    Measured: 12 months

  3. Immune/inflammatory signaling-target gene expression pathways

    RNA/NanoString analysis of targeted gene expression related to activation/function of B cells, T cells, microglia, and other interleukin/ chemokine signaling. Whole blood/CSF will be collected using PAXgene® Blood RNA tubes (Qiagen) shipped to the centers. Total RNA will be extracted using PAXgene® Blood RNA Kit (Qiagen). RNA samples are quantified using Qubit 2.0 Fluorometer (Life Technologies) and RNA integrity is determined with Agilent 2100 Bioanalyzer (Agilent Technologies). Expression levels of 44 genes related to immunological pathways and cytokines (Annex,Table) will be measured with the nCounter® Digital Analyzer (NanoString), as reported (Armangue et al., Mol Genet Metab 2017;122:134-9). Twenty healthy participants will serve as controls (single evaluation).

    Measured: 12 months

  4. NfL levels

    determined in serum and CSF using the SiMoA Quanterix technique, as reported (Guasp et al., Neurology 2022;98:e1489 - 98). Age-and sex-matched healthy participants from previous studies will serve as controls.

    Measured: 12 months

Timeline

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

  1. First posted23 Jul 2024
  2. Study start18 Dec 2023
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Supportive care
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06515106
Sponsor's protocol ID
PI23/00858
Status last verified
Jul 2024
First submitted
26 Mar 2024
Last updated
23 Jul 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Dalmau J, Graus F. Antibody-Mediated Encephalitis. N Engl J Med. 2018 Mar 1;378(9):840-851. doi: 10.1056/NEJMra1708712. No abstract available.

    PubMed 29490181

  • Dalmau J, Geis C, Graus F. Autoantibodies to Synaptic Receptors and Neuronal Cell Surface Proteins in Autoimmune Diseases of the Central Nervous System. Physiol Rev. 2017 Apr;97(2):839-887. doi: 10.1152/physrev.00010.2016.

    PubMed 28298428

  • Hughes EG, Peng X, Gleichman AJ, Lai M, Zhou L, Tsou R, Parsons TD, Lynch DR, Dalmau J, Balice-Gordon RJ. Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis. J Neurosci. 2010 Apr 28;30(17):5866-75. doi: 10.1523/JNEUROSCI.0167-10.2010.

    PubMed 20427647

  • Planaguma J, Leypoldt F, Mannara F, Gutierrez-Cuesta J, Martin-Garcia E, Aguilar E, Titulaer MJ, Petit-Pedrol M, Jain A, Balice-Gordon R, Lakadamyali M, Graus F, Maldonado R, Dalmau J. Human N-methyl D-aspartate receptor antibodies alter memory and behaviour in mice. Brain. 2015 Jan;138(Pt 1):94-109. doi: 10.1093/brain/awu310. Epub 2014 Nov 11.

    PubMed 25392198

  • Petit-Pedrol M, Sell J, Planaguma J, Mannara F, Radosevic M, Haselmann H, Ceanga M, Sabater L, Spatola M, Soto D, Gasull X, Dalmau J, Geis C. LGI1 antibodies alter Kv1.1 and AMPA receptors changing synaptic excitability, plasticity and memory. Brain. 2018 Nov 1;141(11):3144-3159. doi: 10.1093/brain/awy253.

    PubMed 30346486

  • 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.

    PubMed 23290630

  • Granerod J, Ambrose HE, Davies NW, Clewley JP, Walsh AL, Morgan D, Cunningham R, Zuckerman M, Mutton KJ, Solomon T, Ward KN, Lunn MP, Irani SR, Vincent A, Brown DW, Crowcroft NS; UK Health Protection Agency (HPA) Aetiology of Encephalitis Study Group. Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis. 2010 Dec;10(12):835-44. doi: 10.1016/S1473-3099(10)70222-X. Epub 2010 Oct 15.

    PubMed 20952256

  • van Sonderen A, Petit-Pedrol M, Dalmau J, Titulaer MJ. The value of LGI1, Caspr2 and voltage-gated potassium channel antibodies in encephalitis. Nat Rev Neurol. 2017 May;13(5):290-301. doi: 10.1038/nrneurol.2017.43. Epub 2017 Apr 18.

    PubMed 28418022

  • Gable MS, Sheriff H, Dalmau J, Tilley DH, Glaser CA. The frequency of autoimmune N-methyl-D-aspartate receptor encephalitis surpasses that of individual viral etiologies in young individuals enrolled in the California Encephalitis Project. Clin Infect Dis. 2012 Apr;54(7):899-904. doi: 10.1093/cid/cir1038. Epub 2012 Jan 26.

    PubMed 22281844

  • Armangue T, Spatola M, Vlagea A, Mattozzi S, Carceles-Cordon M, Martinez-Heras E, Llufriu S, Muchart J, Erro ME, Abraira L, Moris G, Monros-Gimenez L, Corral-Corral I, Montejo C, Toledo M, Bataller L, Secondi G, Arino H, Martinez-Hernandez E, Juan M, Marcos MA, Alsina L, Saiz A, Rosenfeld MR, Graus F, Dalmau J; Spanish Herpes Simplex Encephalitis Study Group. Frequency, symptoms, risk factors, and outcomes of autoimmune encephalitis after herpes simplex encephalitis: a prospective observational study and retrospective analysis. Lancet Neurol. 2018 Sep;17(9):760-772. doi: 10.1016/S1474-4422(18)30244-8. Epub 2018 Jul 23.

    PubMed 30049614

  • Lai M, Huijbers MG, Lancaster E, Graus F, Bataller L, Balice-Gordon R, Cowell JK, Dalmau J. Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: a case series. Lancet Neurol. 2010 Aug;9(8):776-85. doi: 10.1016/S1474-4422(10)70137-X. Epub 2010 Jun 28.

    PubMed 20580615

  • Irani SR, Alexander S, Waters P, Kleopa KA, Pettingill P, Zuliani L, Peles E, Buckley C, Lang B, Vincent A. Antibodies to Kv1 potassium channel-complex proteins leucine-rich, glioma inactivated 1 protein and contactin-associated protein-2 in limbic encephalitis, Morvan's syndrome and acquired neuromyotonia. Brain. 2010 Sep;133(9):2734-48. doi: 10.1093/brain/awq213. Epub 2010 Jul 27.

    PubMed 20663977

  • Munoz-Sanchez G, Planaguma J, Naranjo L, Couso R, Sabater L, Guasp M, Martinez-Hernandez E, Graus F, Dalmau J, Ruiz-Garcia R. The diagnosis of anti-LGI1 encephalitis varies with the type of immunodetection assay and sample examined. Front Immunol. 2022 Dec 15;13:1069368. doi: 10.3389/fimmu.2022.1069368. eCollection 2022.

    PubMed 36591253

  • van Sonderen A, Thijs RD, Coenders EC, Jiskoot LC, Sanchez E, de Bruijn MA, van Coevorden-Hameete MH, Wirtz PW, Schreurs MW, Sillevis Smitt PA, Titulaer MJ. Anti-LGI1 encephalitis: Clinical syndrome and long-term follow-up. Neurology. 2016 Oct 4;87(14):1449-1456. doi: 10.1212/WNL.0000000000003173. Epub 2016 Sep 2.

    PubMed 27590293

  • Arino H, Armangue T, Petit-Pedrol M, Sabater L, Martinez-Hernandez E, Hara M, Lancaster E, Saiz A, Dalmau J, Graus F. Anti-LGI1-associated cognitive impairment: Presentation and long-term outcome. Neurology. 2016 Aug 23;87(8):759-65. doi: 10.1212/WNL.0000000000003009. Epub 2016 Jul 27.

    PubMed 27466467

Questions about this trial

What is this clinical trial studying?

A study testing Remote cognitive rehabilitation program in people with Limbic Encephalitis With LGI1 Antibodies, run by Fundacion Clinic per a la Recerca Biomédica at 1 site in Spain.

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 2 inclusion and 2 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: looking for participants now, as of the sponsor's last update on 23 Jul 2024. 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 Spain. 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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Josep Dalmau, MD,PhD (34 93 227 1738, jdalmau@clinic.cat), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Age (time frame: 12 months). The study lists 79 primary outcomes in all. 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 NCT06515106, which also lists 22 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 23 Jul 2024.

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