Autoimmune EncephalitisICARE-IINCT04823728
HLA Analysis in Autoimmune Encephalitis and Related Disorders: Part II
An observational study of Autoimmune Encephalitis and Paraneoplastic Neurological Syndrome, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
Autoimmune encephalitis (AE) are characterized by subacute onset of memory deficits, altered mental status or psychiatric symptoms, frequently associated with seizures, inflammatory cerebrospinal fluid and in cases with prominent limbic involvement, typical magnetic resonance imaging. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Autoimmune Encephalitis, Paraneoplastic Neurological Syndrome
- What is being tested?
- Autoimmune encephalitis and paraneoplastic neurological syndromes
- How many people
- 700 participants
- Where
- 1 siteFrance
- Study dates
- 1 Jan 2021to 31 Dec 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients older than 18 years, having well-characterized anti-neural or anti-glial antibodies in serum and/or CSF detected in our laboratory, presenting with well-defined clinical pictures considered as associated with the aforementioned antibodies by a physician (neurologist) from the French Reference Center, including the presence of cancer in the case of paraneoplastic neurological syndromes; and whose clinical data is stocked at the database of our center.
Who may be able to join
- Presence of well-characterized antibodies in serum or cerebrospinal fluid;
- Clinical picture compatible with the detected antibody based on the literature;
- For PNS, cancer detected and compatible with the detected antibody based on the literature
Who cannot join
- Absence of complete clinicobiological data.
- Incongruences between antibody-clinics or antibody-cancer
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Hôpital Neurologique
Bron, 69677
Jerome HONNORAT, MD, 4 72 35 78 08 ext. +33, jerome.honnorat@chu-lyon.fr
About this study
Official title: Immunogenetic Characteristics in Autoimmune Encephalitis and Related Disorders: HLA Analysis: Part II
Autoimmune encephalitis (AE) are characterized by subacute onset of memory deficits, altered mental status or psychiatric symptoms, frequently associated with seizures, inflammatory cerebrospinal fluid and in cases with prominent limbic involvement, typical magnetic resonance imaging. Several autoantibodies (Abs) may be detected in AE, although its detection is not mandatory to establish a diagnosis. These Abs mainly recognize different synaptic and cell-surface proteins in the central nervous system, and are thought to be pathogenic as they alter the normal location or function of its antigens. Paraneoplastic neurological syndromes (PNS) are immune-mediated, remote complications of cancer. The clinical presentation is highly diverse, from central nervous system disorders (limbic encephalitis, cerebellar ataxia) to peripheral neuropathies and neuromuscular junction diseases. Two different kinds of Abs are associated with PNS: a first group known as onconeural Abs, which recognize intracellular antigens and are thought not to be pathogenic; and a second one whose targeted synaptic and cell-surface antigens shared with some non-paraneoplastic AE.
The primary trigger of the immune response is unknown for most of AE. In addition to acquired susceptibility such as herpes simplex encephalitis, genetic predisposition may also be important in the pathogenesis of AE. Human leukocyte antigen (HLA) is the genetic factor most frequently associated with autoimmune diseases, due to its genetic complexity and key role in the adaptive immune response. Others and we already described the HLA haplotypes associated with three types different of AE: anti-leucine-rich glioma inactivated 1 (LGI1), anti-contactin-associated protein-like 2 (CASPR2), and anti-glutamic acid decarboxylase (GAD). Nevertheless, the genetic predisposition of many other AE has not been investigated yet.
Cancer is considered as the trigger of the immune response that lead to PNS development, as the neural antigens recognized by the onconeural Abs are also expressed by tumor cells. Nevertheless, it is still unknown why some patients develop PNS and others do not, even if they present the same histological type of tumor, suggesting that some particular, maybe genetic, characteristics of the patients may play a role in this susceptibility. Furthermore, there is already evidence that, for those neurological diseases that may appear either as PNS or as non-paraneoplastic autoimmune disorder (i.e. Lambert-Eaton myasthenic syndrome), HLA profiles are not the same.
- Being tested
- Autoimmune encephalitis and paraneoplastic neurological syndromes
- Keywords
- Autoimmune encephalitis, Paraneoplastic neurological syndromes
- Medical subject headings
- Autoimmune Diseases of the Nervous System
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autoimmune encephalitis and paraneoplastic neurological syndromesGenetic
This is a non-interventional study involving biological samples (DNA). Samples are already stored in biobank repositories and collected as part of "good clinical practice" in the diagnostic process of patients with suspected autoimmune encephalitis, meaning that the standard diagnostic and therapeutic approaches will not be altered in the selected study population. Patients have already gave explicit written consent for biological specimens sampling and storage at the "Centre de Ressources Biologiques des Hospices Civils de Lyon" (CRB-HCL)/NeuroBioTec (including tissue, cells or biological fluids) and genetic analysis for research purposes (e.g. involving genes related to the disease for which the patient was followed). Additionally, patients will be informed about the present study.
| Study group | Role | What they receive |
|---|---|---|
| Autoimmune encephalitis and paraneoplastic neurological syndromes | Patients with well-characterized antibodies against onconeural antigens, synaptic or cell-surface antigens Receives: Genetic: Autoimmune encephalitis and paraneoplastic neurological syndromes |
What is being measured
The primary outcome is the main question the study is designed to answer.
Description of HLA alleles and haplotypes carrier frequencies in autoimmune encephalitis and paraneoplastic neurological syndromes.
Analyze the distribution of all HLA alleles at the level of the main HLA susceptibility loci, HLA A, B, C, DR, DQ and DP in all patients with AE or PNS.
Measured: 5 years. M1-M24: clinical database review, DNA extraction M25-M36: HLA analysis M37-M60: statistical analysis, combined analysis of genetic and clinical data
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2021
- Study start1 Jan 2021
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Autoimmune EncephalitisStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 700 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04823728
- Sponsor's protocol ID
- 69HCL20_0826
- Acronym
- ICARE-II
- Status last verified
- Mar 2021
- First submitted
- 26 Mar 2021
- Last updated
- 1 Apr 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunogenetic Characteristics in Autoimmune Encephalitis and Related Disorders: HLA Analysis: Part II
- ClinicalTrials.gov ID
- NCT04823728
- Acronym / sponsor ID
- ICARE-II / 69HCL20_0826
- Keywords
- Autoimmune encephalitis, Paraneoplastic neurological syndromes
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 700 participants (estimated)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 1 Jan 2021 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 1 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Autoimmune encephalitis (AE) are characterized by subacute onset of memory deficits, altered mental status or psychiatric symptoms, frequently associated with seizures, inflammatory cerebrospinal fluid and in cases with prominent limbic involvement, typical magnetic resonance imaging. Several autoantibodies (Abs) may be detected in AE, although its detection is not mandatory to establish a diagnosis. These Abs mainly recognize different synaptic and cell-surface proteins in the central nervous system, and are thought to be pathogenic as they alter the normal location or function of its antigens. Paraneoplastic neurological syndromes (PNS) are immune-mediated, remote complications of cancer. The clinical presentation is highly diverse, from central nervous system disorders (limbic encephalitis, cerebellar ataxia) to peripheral neuropathies and neuromuscular junction diseases. Two different kinds of Abs are associated with PNS: a first group known as onconeural Abs, which recognize intracellular antigens and are thought not to be pathogenic; and a second one whose targeted synaptic and cell-surface antigens shared with some non-paraneoplastic AE.
The primary trigger of the immune response is unknown for most of AE. In addition to acquired susceptibility such as herpes simplex encephalitis, genetic predisposition may also be important in the pathogenesis of AE. Human leukocyte antigen (HLA) is the genetic factor most frequently associated with autoimmune diseases, due to its genetic complexity and key role in the adaptive immune response. Others and we already described the HLA haplotypes associated with three types different of AE: anti-leucine-rich glioma inactivated 1 (LGI1), anti-contactin-associated protein-like 2 (CASPR2), and anti-glutamic acid decarboxylase (GAD). Nevertheless, the genetic predisposition of many other AE has not been investigated yet.
Cancer is considered as the trigger of the immune response that lead to PNS development, as the neural antigens recognized by the onconeural Abs are also expressed by tumor cells. Nevertheless, it is still unknown why some patients develop PNS and others do not, even if they present the same histological type of tumor, suggesting that some particular, maybe genetic, characteristics of the patients may play a role in this susceptibility. Furthermore, there is already evidence that, for those neurological diseases that may appear either as PNS or as non-paraneoplastic autoimmune disorder (i.e. Lambert-Eaton myasthenic syndrome), HLA profiles are not the same.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Autoimmune encephalitis and paraneoplastic neurological syndromes | – | Genetic: Autoimmune encephalitis and paraneoplastic neurological syndromesPatients with well-characterized antibodies against onconeural antigens, synaptic or cell-surface antigens |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients older than 18 years, having well-characterized anti-neural or anti-glial antibodies in serum and/or CSF detected in our laboratory, presenting with well-defined clinical pictures considered as associated with the aforementioned antibodies by a physician (neurologist) from the French Reference Center, including the presence of cancer in the case of paraneoplastic neurological syndromes; and whose clinical data is stocked at the database of our center.
Key inclusion criteria (3 listed)
- Presence of well-characterized antibodies in serum or cerebrospinal fluid;
- Clinical picture compatible with the detected antibody based on the literature;
- For PNS, cancer detected and compatible with the detected antibody based on the literature
Key exclusion criteria (2 listed)
- Absence of complete clinicobiological data.
- Incongruences between antibody-clinics or antibody-cancer
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Autoimmune encephalitis and paraneoplastic neurological syndromesThis is a non-interventional study involving biological samples (DNA). Samples are already stored in biobank repositories and collected as part of "good clinical practice" in the diagnostic process of patients with suspected autoimmune encephalitis, meaning that the standard diagnostic and therapeutic approaches will not be altered in the selected study population. Patients have already gave explicit written consent for biological specimens sampling and storage at the "Centre de Ressources Biologiques des Hospices Civils de Lyon" (CRB-HCL)/NeuroBioTec (including tissue, cells or biological fluids) and genetic analysis for research purposes (e.g. involving genes related to the disease for which the patient was followed). Additionally, patients will be informed about the present study. | Genetic | Autoimmune encephalitis and paraneoplastic neurological syndromes |
Primary outcome
Description of HLA alleles and haplotypes carrier frequencies in autoimmune encephalitis and paraneoplastic neurological syndromes.
Time frame: 5 years. M1-M24: clinical database review, DNA extraction M25-M36: HLA analysis M37-M60: statistical analysis, combined analysis of genetic and clinical data
Analyze the distribution of all HLA alleles at the level of the main HLA susceptibility loci, HLA A, B, C, DR, DQ and DP in all patients with AE or PNS.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Autoimmune Encephalitis and Paraneoplastic Neurological Syndrome, run by Hospices Civils de Lyon at 1 site in France.
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 3 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: status not confirmed, as of the sponsor's last update on 1 Apr 2021. 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 France. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jerome HONNORAT, MD (4 72 35 78 08 ext. +33, jerome.honnorat@chu-lyon.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Description of HLA alleles and haplotypes carrier frequencies in autoimmune encephalitis and paraneoplastic neurological syndromes. (time frame: 5 years. M1-M24: clinical database review, DNA extraction M25-M36: HLA analysis M37-M60: statistical analysis, combined analysis of genetic and clinical data). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Apr 2021.