NMO Spectrum DisorderSTANDNCT05414890
Sensitivity and Specificity of TSA-CBA for Autoantibodies Against Neural Antigen Determination
An observational study of NMO Spectrum Disorder and NMDA-R Encephalitis, run by Beijing Tiantan Hospital at 1 site in China.
Trial summary
Determination of autoantibodies against fragments derived from neurons, glia, and myelin sheath is instrumental in aiding diagnosis, differential diagnosis, as well as determining disease status of neuromyelitis optica spectrum disorders (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- NMO Spectrum Disorder, NMDA-R Encephalitis, Diagnostic Self Evaluation
- What is being tested?
- CBA-TSA
- How many people
- 2,500 participants
- Where
- 1 siteChina
- Study dates
- 30 Jun 2022to 30 Jun 2024
- 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
- Healthy volunteers accepted
- Adult, Older adult
Study population: The patients with CNS demyelinating autoimmune diseases (NMOSD, MOGAD, AE)
Who may be able to join
- The patients with suspected NMOSD, MOGAD and AE will be recruited.
- Male and female patients, ≥ 18 years old.
Who cannot join
- Abnormal sera, such as hemolysis or lipemia, which will affect the final interpretation of CBA and CBA-TSA;
- The samples with incomplete clinical data that would affect the disease characterization.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Beijing Tiantan Hospital
Beijing, Beijing Municipality, 100010
Fu-Dong Shi, PhD, +861059976585, fshi@tmu.edu.cn
About this study
Official title: Comparison of the Specificity, Sensitivity, and Clinical Correlation of Cell-based Assay (CBA) and CBA-TSA (Tyramide Signal Amplification) in Detecting AQP4, MOG, and NMDAR-IgG in Central Nervous System Diseases; a National Multicenter Study
Determination of autoantibodies against fragments derived from neurons, glia, and myelin sheath is instrumental in aiding diagnosis, differential diagnosis, as well as determining disease status of neuromyelitis optica spectrum disorders (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), autoimmune encephalitis (AE). Cell based assay (CBA) has been frequently recommended to detect autoantibodies of neuroantigens in the aforementioned neurological disorders. However, antibodies with low abundance or low affinity often fall beyond the threshold of CBA and pose significant challenges in practice. To this end, the investigators adopted a tyramide signal amplification (TSA) technology with the basis of CBA to improve sensitivity. The preliminary results suggest that this TSA-CBA platform is superior to conventional CBA in registered signals of the titer autoantibodies. In elevating the sensitivity, TSA-CBA also preserves antigen confirmation. This prospective study is launched to compare the sensitivity, specificity, clinical correlation between CBA and CBA-TSA, in determining autoantibodies against aquaporin 4 (AQP4-IgG), myelin oligodendrocyte glycoprotein (MOG-IgG), N-methyl-D-aspartate receptor (NMDAR-IgG) in a multicenter, double-blind setting.
Read the detailed description
Participants: The sera of patients with CNS demyelinating autoimmune diseases (NMOSD, MOGAD, AE).
Primary aim: 1) Compare the specificity, sensitivity, and clinical correlation between CBA and CBA-TSA, in detecting AQP4, MOG, and NMDAR IgG. 2) Analyze the advantage of CBA-TSA assay over conventional CBA in detecting antibodies to AQP4, MOG, and NMDAR IgG with low abundance and low affinity.
Secondary aim: Comparison of the turn-around time and the cost of CBA and CBA-TSA in detecting AQP4, MOG, and NMDAR IgG.
Study design: Multicenter, double-blind, CBA and CBA-TSA methodology comparison
Total cases:
- 1000 patients with suspected NMOSD, MOGAD and 1000 patients with suspected autoimmune encephalitis (AE) will be recruited.
- 500 normal subjects will be recruited.
Trial Period: The trial recruiting duration is 1-2 years.
Research reagents: 1. The reagents for of AQP4, MOG or NMDAR IgG antibody detection via CBA have been developed and validated by the joint effort of Bejing Tiantan Hospital, Tianjin General Hospital, and Tianjin New Terrain Biological Technology Co., Ltd, China , will be adopted by this study. 2. The CBA-TSA antibody IgG assay developed by the three entities and will be adopted for this study
Groups: The sera samples from patients and control subjects, upon clinic visits, as well as during follow up, will be randomly numbered. All samples will be blindly tested with CBA-TSA and CBA by different operators.
Study Steps:
- Patients recruiting: 1000 patients with suspected NMOSD, MOGAD and 1000 patients with suspected AE will be recruited according to inclusion/exclusion criteria.
- CBA/CBA-TSA assay: Sera samples from patients and control subjects will be randomly numbered and divided into 3 equal parts (500 ul/part). All samples will be tested with CBA-TSA and CBA by different blinded operators; original value, control value, turn-around time and cost will all be recorded. The difference comparison between CBA and CBA-TSA was completed by Bejing Tiantan Hospital.
- Statistical Methods: Each center will provide feedback of the clinical diagnosis and treatment data of the participants to the investigator. The investigator will complete the evaluation of respective clinical correlation of the CBA and CBA-TSA methods. The statistics and operation of the project are supervised by a third-party audit company.
- Conditions
- NMO Spectrum Disorder, NMDA-R Encephalitis, Diagnostic Self Evaluation, Immune System Diseases, Nervous System Diseases, Autoimmune Diseases of the Nervous System
- Being tested
- CBA-TSA
- Medical subject headings
- Neuromyelitis Optica, Immune System Diseases, Nervous System Diseases, Autoimmune Diseases of the Nervous System, Autoimmune Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CBA-TSADiagnostic test
Compare the specificity, sensitivity, and clinical correlation between CBA and CBA-TSA, in detecting AQP4, MOG, and NMDAR IgG
| Study group | Role | What they receive |
|---|---|---|
| Cell Based Assay (CBA) | The sera samples from patients and control subjects, upon clinic visits, as well as during follow up, will be randomly numbered. All samples will be blindly tested with CBA by different operators. | |
| CBA-TSA Assay | The sera samples from patients and control subjects, upon clinic visits, as well as during follow up, will be randomly numbered. All samples will be blindly tested with CBA-TSA by different operators. Receives: Diagnostic Test: CBA-TSA |
What is being measured
The primary outcome is the main question the study is designed to answer.
CBA-TSA is consistent with CBA in terms of specificity and clinical correlation in detecting autoantibodies.
Comparsion the specificity, sensitivity, positive likelihood ratio (LR), negative LR and clinical correlation of CBA and CBA-TSA assay in autoantibodies detection of AQP4, MOG, NMDAR respectively.
Measured: 2022.6.30-2024.6.30
CBA-TSA is superior to CBA for detecting antibodies to AQP4, MOG, and NMDAR IgG with low abundance and low affinity.
Comparsion the sensitivity of CBA and CBA-TSA assay in detecting the AQP4, MOG or NMDAR IgG in low abundance and low affinity.
Measured: 2022.6.30-2024.6.30
Secondary outcomes (1)
Compared with CBA, CBA-TSA uses a smaller sample and costs less, but the experiment turn-around time takes longer.
Comparsion the detection time, costs and sample usage of CBA and CBA-TSA assay in autoantibodies detection of AQP4, MOG, NMDAR.
Measured: 2022.6.30-2024.6.30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2022
- Study start30 Jun 2022 (estimated)
- Primary completion30 Jan 2024 (estimated)
- Study completion30 Jun 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for NMO Spectrum DisorderStudies of the same condition, open and under way.
- More trials run by Beijing Tiantan HospitalThe 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 2,500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Tiantan Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Tianjin Medical University General Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05414890
- Sponsor's protocol ID
- IRB2022-YX-066-01
- Acronym
- STAND
- Status last verified
- Jun 2022
- First submitted
- 31 May 2022
- Last updated
- 10 Jun 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Zhang C, Tian DC, Yang CS, Han B, Wang J, Yang L, Shi FD. Safety and Efficacy of Bortezomib in Patients With Highly Relapsing Neuromyelitis Optica Spectrum Disorder. JAMA Neurol. 2017 Aug 1;74(8):1010-1012. doi: 10.1001/jamaneurol.2017.1336.
PubMed 28692708Zhang C, Zhang M, Qiu W, Ma H, Zhang X, Zhu Z, Yang CS, Jia D, Zhang TX, Yuan M, Feng Y, Yang L, Lu W, Yu C, Bennett JL, Shi FD; TANGO Study Investigators. Safety and efficacy of tocilizumab versus azathioprine in highly relapsing neuromyelitis optica spectrum disorder (TANGO): an open-label, multicentre, randomised, phase 2 trial. Lancet Neurol. 2020 May;19(5):391-401. doi: 10.1016/S1474-4422(20)30070-3.
PubMed 32333897
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of the Specificity, Sensitivity, and Clinical Correlation of Cell-based Assay (CBA) and CBA-TSA (Tyramide Signal Amplification) in Detecting AQP4, MOG, and NMDAR-IgG in Central Nervous System Diseases; a National Multicenter Study
- ClinicalTrials.gov ID
- NCT05414890
- Acronym / sponsor ID
- STAND / IRB2022-YX-066-01
- Conditions
- NMO Spectrum Disorder, NMDA-R Encephalitis, Diagnostic Self Evaluation, Immune System Diseases, Nervous System Diseases, Autoimmune Diseases of the Nervous System
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 2,500 participants (estimated)
- Lead sponsor
- Beijing Tiantan HospitalUniversity, hospital or other
- Collaborators
- Tianjin Medical University General Hospital
- Study start
- 30 Jun 2022 (estimated)
- Primary completion
- 30 Jan 2024 (estimated)
- Study completion
- 30 Jun 2024 (estimated)
- First posted
- 10 Jun 2022 (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.
Determination of autoantibodies against fragments derived from neurons, glia, and myelin sheath is instrumental in aiding diagnosis, differential diagnosis, as well as determining disease status of neuromyelitis optica spectrum disorders (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), autoimmune encephalitis (AE). Cell based assay (CBA) has been frequently recommended to detect autoantibodies of neuroantigens in the aforementioned neurological disorders. However, antibodies with low abundance or low affinity often fall beyond the threshold of CBA and pose significant challenges in practice. To this end, the investigators adopted a tyramide signal amplification (TSA) technology with the basis of CBA to improve sensitivity. The preliminary results suggest that this TSA-CBA platform is superior to conventional CBA in registered signals of the titer autoantibodies. In elevating the sensitivity, TSA-CBA also preserves antigen confirmation. This prospective study is launched to compare the sensitivity, specificity, clinical correlation between CBA and CBA-TSA, in determining autoantibodies against aquaporin 4 (AQP4-IgG), myelin oligodendrocyte glycoprotein (MOG-IgG), N-methyl-D-aspartate receptor (NMDAR-IgG) in a multicenter, double-blind setting.
Detailed description
Participants: The sera of patients with CNS demyelinating autoimmune diseases (NMOSD, MOGAD, AE).
Primary aim: 1) Compare the specificity, sensitivity, and clinical correlation between CBA and CBA-TSA, in detecting AQP4, MOG, and NMDAR IgG. 2) Analyze the advantage of CBA-TSA assay over conventional CBA in detecting antibodies to AQP4, MOG, and NMDAR IgG with low abundance and low affinity.
Secondary aim: Comparison of the turn-around time and the cost of CBA and CBA-TSA in detecting AQP4, MOG, and NMDAR IgG.
Study design: Multicenter, double-blind, CBA and CBA-TSA methodology comparison
Total cases:
- 1000 patients with suspected NMOSD, MOGAD and 1000 patients with suspected autoimmune encephalitis (AE) will be recruited.
- 500 normal subjects will be recruited.
Trial Period: The trial recruiting duration is 1-2 years.
Research reagents: 1. The reagents for of AQP4, MOG or NMDAR IgG antibody detection via CBA have been developed and validated by the joint effort of Bejing Tiantan Hospital, Tianjin General Hospital, and Tianjin New Terrain Biological Technology Co., Ltd, China , will be adopted by this study. 2. The CBA-TSA antibody IgG assay developed by the three entities and will be adopted for this study
Groups: The sera samples from patients and control subjects, upon clinic visits, as well as during follow up, will be randomly numbered. All samples will be blindly tested with CBA-TSA and CBA by different operators.
Study Steps:
- Patients recruiting: 1000 patients with suspected NMOSD, MOGAD and 1000 patients with suspected AE will be recruited according to inclusion/exclusion criteria.
- CBA/CBA-TSA assay: Sera samples from patients and control subjects will be randomly numbered and divided into 3 equal parts (500 ul/part). All samples will be tested with CBA-TSA and CBA by different blinded operators; original value, control value, turn-around time and cost will all be recorded. The difference comparison between CBA and CBA-TSA was completed by Bejing Tiantan Hospital.
- Statistical Methods: Each center will provide feedback of the clinical diagnosis and treatment data of the participants to the investigator. The investigator will complete the evaluation of respective clinical correlation of the CBA and CBA-TSA methods. The statistics and operation of the project are supervised by a third-party audit company.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cell Based Assay (CBA) | – | –The sera samples from patients and control subjects, upon clinic visits, as well as during follow up, will be randomly numbered. All samples will be blindly tested with CBA by different operators. |
| CBA-TSA Assay | – | Diagnostic Test: CBA-TSAThe sera samples from patients and control subjects, upon clinic visits, as well as during follow up, will be randomly numbered. All samples will be blindly tested with CBA-TSA by different operators. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The patients with CNS demyelinating autoimmune diseases (NMOSD, MOGAD, AE)
Key inclusion criteria (2 listed)
- The patients with suspected NMOSD, MOGAD and AE will be recruited.
- Male and female patients, ≥ 18 years old.
Key exclusion criteria (2 listed)
- Abnormal sera, such as hemolysis or lipemia, which will affect the final interpretation of CBA and CBA-TSA;
- The samples with incomplete clinical data that would affect the disease characterization.
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 |
|---|---|---|
| CBA-TSACompare the specificity, sensitivity, and clinical correlation between CBA and CBA-TSA, in detecting AQP4, MOG, and NMDAR IgG | Diagnostic test | CBA-TSA Assay |
Primary outcome
CBA-TSA is consistent with CBA in terms of specificity and clinical correlation in detecting autoantibodies.
Time frame: 2022.6.30-2024.6.30
Comparsion the specificity, sensitivity, positive likelihood ratio (LR), negative LR and clinical correlation of CBA and CBA-TSA assay in autoantibodies detection of AQP4, MOG, NMDAR respectively.
CBA-TSA is superior to CBA for detecting antibodies to AQP4, MOG, and NMDAR IgG with low abundance and low affinity.
Time frame: 2022.6.30-2024.6.30
Comparsion the sensitivity of CBA and CBA-TSA assay in detecting the AQP4, MOG or NMDAR IgG in low abundance and low affinity.
1 secondary outcome
Compared with CBA, CBA-TSA uses a smaller sample and costs less, but the experiment turn-around time takes longer.
Time frame: 2022.6.30-2024.6.30
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2022.
- Background: PubMed 28692708Zhang C, Tian DC, Yang CS, Han B, Wang J, Yang L, Shi FD. Safety and Efficacy of Bortezomib in Patients With Highly Relapsing Neuromyelitis Optica Spectrum Disorder. JAMA Neurol. 2017 Aug 1;74(8):1010-1012. doi: 10.1001/jamaneurol.2017.1336.
- Background: PubMed 32333897Zhang C, Zhang M, Qiu W, Ma H, Zhang X, Zhu Z, Yang CS, Jia D, Zhang TX, Yuan M, Feng Y, Yang L, Lu W, Yu C, Bennett JL, Shi FD; TANGO Study Investigators. Safety and efficacy of tocilizumab versus azathioprine in highly relapsing neuromyelitis optica spectrum disorder (TANGO): an open-label, multicentre, randomised, phase 2 trial. Lancet Neurol. 2020 May;19(5):391-401. doi: 10.1016/S1474-4422(20)30070-3.
- Individual participant dataSharing planned: No
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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 NMO Spectrum Disorder and NMDA-R Encephalitis, run by Beijing Tiantan Hospital at 1 site in China.
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: status not confirmed, as of the sponsor's last update on 10 Jun 2022. 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 China. 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 Fu-Dong Shi (+861059976585, fshi@tmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CBA-TSA is consistent with CBA in terms of specificity and clinical correlation in detecting autoantibodies. (time frame: 2022.6.30-2024.6.30). The study lists 2 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 NCT05414890, which also lists 2 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 10 Jun 2022.