Trial Title:
Antibody-mediated LGI1 Encephalitis: Symptoms, Biomarkers, and Mechanisms of the Chronic Phase of the Disease
NCT ID:
NCT06515106
Condition:
Limbic Encephalitis With LGI1 Antibodies
Conditions: Official terms:
Limbic Encephalitis
Encephalitis
Conditions: Keywords:
Cognitive Impairment
Encephalitis
Autoimmune
Cognitive rehabilitation
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Supportive Care
Masking:
None (Open Label)
Intervention:
Intervention type:
Behavioral
Intervention name:
Remote cognitive rehabilitation program
Description:
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).
Arm group label:
Antibody-mediated LGI1 encephalitis patients
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. 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.
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients with Antibody-mediated LGI-1 encephalitis in the post-acute stage of the
disease;
- Patients has been discharged from hospital (acute phase).
Exclusion Criteria:
- Inability to obtain informed consent;
- Inability to travel to the center.
Gender:
All
Minimum age:
N/A
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Hospital Clínic de Barcelona
Address:
City:
Barcelona
Zip:
08036
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Josep Dalmau, MD, PhD
Phone:
+34 93 227 1738
Email:
jdalmau@clinic.cat
Contact backup:
Last name:
Victor Patricio, MS
Phone:
+34 93 227 1738
Email:
vpatricio@recerca.clinic.cat
Investigator:
Last name:
Josep Dalmau, MD, PhD
Email:
Principal Investigator
Investigator:
Last name:
Lorena Rami, PhD
Email:
Principal Investigator
Investigator:
Last name:
Mar Guasp, MD, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Eugenia Martínez-Hernández, MD, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Thais Armanguè, MD, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Amaia Muñoz, MD
Email:
Sub-Investigator
Investigator:
Last name:
Laia Prades, MS
Email:
Sub-Investigator
Investigator:
Last name:
Víctor Patricio, MS
Email:
Sub-Investigator
Investigator:
Last name:
Elianet Fonseca, MD
Email:
Sub-Investigator
Start date:
December 18, 2023
Completion date:
December 31, 2026
Lead sponsor:
Agency:
Fundacion Clinic per a la Recerca Biomédica
Agency class:
Other
Source:
Fundacion Clinic per a la Recerca Biomédica
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06515106
