NeurosyphilisNCT06152393
Value of an Intrathecal Synthesis Index of Specific Antitreponema IgG for Neurosyphilis Diagnosis
An observational study of Neurosyphilis, run by University Hospital, Geneva at 1 site in Switzerland.
Trial summary
A retro-prospective case-control Swiss study was conducted to evaluate the diagnostic performance of measuring an antibody index (AI) for intrathecal synthesis of specific anti-Treponema pallidum (T. pallidum) IgG for the diagnosis of neurosyphilis. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Neurosyphilis
- What is being tested?
- Measure of an antibody index for intrathecal synthesis of specific anti-Treponema pallidum IgG by ELISA.
- How many people
- 181 participants
- Where
- 1 siteSwitzerland
- Study dates
- 1 Mar 2019to 31 Dec 2022
- 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: This is a bidirectional retrospective and prospective multicenter study, including all the patients presenting neurological and neuro-sensory signs (ophthalmic and auditory), for whom we have serum and cerebrospinal fluid samples, from the University Hospitals of Geneva, Zurich and Lausanne, at the ADMED Microbiology Laboratory of La Chaux-de-Fonds and in SHCS centers.
Who may be able to join
- All patients who have serum / CSF sample pairs collected concomitantly (3 days maximum interval between blood test and lumbar puncture).
- Age > or = 18 years old.
Who cannot join
- All patients for whom the stored samples do not meet the needs of the diagnostic study, or whose serum and CSF collection date is more than 3 consecutive days.
- Age < 18 years old.
- No written consent form for the prospective part.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Retro-prospective Multicentric Study Aiming to Evaluate the Benefit of Measuring an Intrathecal Synthesis Index of Specific Antitreponema IgG for Patients Suspected of Neurosyphilis
A retro-prospective case-control Swiss study was conducted to evaluate the diagnostic performance of measuring an antibody index (AI) for intrathecal synthesis of specific anti-Treponema pallidum (T. pallidum) IgG for the diagnosis of neurosyphilis.
Read the detailed description
The diagnosis of neurosyphilis (NS) lacks a true "gold standard" which makes the diagnosis challenging while consequences of a misdiagnosis are potentially severe. The aim of this study was to evaluate the diagnostic performance of measuring an antibody index (AI) for intrathecal synthesis of specific anti-Treponema pallidum (T. pallidum) IgG for the diagnosis of NS.
CSF parameters were analysed and specific anti-T. pallidum IgG were measured simultaneously on paired cerebrospinal fluid (CSF)-serum samples collected between 2007 and 2022 from patients suspected of NS, in Switzerland. An AI was calculated to consider blood-brain barrier integrity. Two NS definitions were used: NS1 included patients with suspicion of NS presenting neurological symptoms and/or acute neuro-sensory signs and positive TPHA/TPPA serology and CSF-TPHA/TPPA≥320, and either CSF-leucocytes >5cells/mm3 and/or CSF-protein >0,45g/l and/or a reactive CSF-VDRL/RPR test. NS2 included patients with NS suspicion presenting acute ocular and/or otologic symptoms, and positive TPHA/TPPA serology, and a favourable response to NS treatment. Controls were patients diagnosed with any other CNS pathologies and with positive TPHA/TPPA serology.
- Conditions
- Neurosyphilis
- Being tested
- Measure of an antibody index for intrathecal synthesis of specific anti-Treponema pallidum IgG by ELISA.
- Keywords
- Neurosyphilis, Treponema pallidum, Intrathecal synthesis, Specific anti-Treponema IgG, Otosyphilis, Ocular syphilis
- Medical subject headings
- Neurosyphilis, Treponemal Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Measure of an antibody index for intrathecal synthesis of specific anti-Treponema pallidum IgG by ELISA.Diagnostic test
Paired CSF/serum samples from all patients were blind tested for anti-T. pallidum IgG with an ELISA containing recombinant T. pallidum proteins (Euroimmun).
The AI was calculated conforming to Reiber's method (PMID 11239944) and as previously described in Alberto et al. (PMID 35138118).
| Study group | Role | What they receive |
|---|---|---|
| Control patients | Controls were patients diagnosed with TPHA/TPPA serology ≥80 and neurological symptoms requiring a lumbar puncture. Receives: Diagnostic Test: Measure of an antibody index for intrathecal synthesis of specific anti-Treponema pallidum IgG by ELISA. | |
| NS1 patients | NS1 includes: 1) neurological symptoms suggestive of central nervous system (CNS) involvement or acute ophthalmological or acute auditory signs consistent with neurosyhilis (NS), or syphilis with treatment serological failure (< fourfold decrease in the antibody titer of RPR/VDRL 12 months after treatment), and 2) a TPHA/TPPA serology ≥ 80 and a CSF-TPHA/TPPA test ≥ 320, and 3) either CSF-WBC > 5 cells/mm3, and/or CSF-protein > 0,45g/l in the absence of other known causes of these abnormalities, and/or a reactive CSF-VDRL/RPR test, and 4) no differential diagnosis. Receives: Diagnostic Test: Measure of an antibody index for intrathecal synthesis of specific anti-Treponema pallidum IgG by ELISA. | |
| NS2 patients | NS2 includes:1) acute ocular symptoms (recent and sudden decrease in visual acuity) and/or acute otologic dysfunctions (sudden hearing loss, acute tinnitus or vertigo) without other known diagnosis for these clinical abnormalities, 2) and a TPHA/TPPA serology ≥ 80, 3) and a response to NS treatment assessed by ophthalmologic or hearing tests and at least a fourfold reduction of RPR/VDRL titer in blood after 12 months following treatment. Receives: Diagnostic Test: Measure of an antibody index for intrathecal synthesis of specific anti-Treponema pallidum IgG by ELISA. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of the diagnostic performance of measuring an antibody index (AI) for intrathecal synthesis of specific anti-Treponema pallidum IgG for the diagnosis of neurosyphilis.
AI testing measured with an Elisa specific for anti-Treponema pallidum IgG for all patients : number of patients with positive AI, sensitivity/specificity of the test, and positive/negative predictive values of AI test were estimated.
Measured: 2020-2022 with retrospective samples from 2007 to 2019 and prospective samples from 2019 to 2022.
Secondary outcomes (1)
Intrathecal oligoclonal IgG production analysis
IgG oligoclonal bands were analysed in CSF and serum of NS and control patients by the gold standard isoelectric focusing method
Measured: 2020-2022 with retrospective samples from 2007 to 2019 and prospective samples from 2019 to 2022.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2023
- Study start1 Mar 2019
- Primary completion31 Dec 2022
- Study completion31 Dec 2022
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 NeurosyphilisStudies of the same condition, open and under way.
- More trials run by University Hospital, GenevaThe 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
- Other
- Enrolment
- 181 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Geneva
- Sponsor type
- University, hospital or other
- Collaborators
- Swiss HIV Cohort Study, Swiss National Science Foundation
- Responsible party
- Principal investigator, Laurence Toutous Trellu, University Hospital, Geneva
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06152393
- Sponsor's protocol ID
- Study 2019-00232
- Status last verified
- Nov 2023
- First submitted
- 12 Oct 2023
- Last updated
- 30 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Reiber H, Peter JB. Cerebrospinal fluid analysis: disease-related data patterns and evaluation programs. J Neurol Sci. 2001 Mar 1;184(2):101-22. doi: 10.1016/s0022-510x(00)00501-3.
PubMed 11239944Alberto C, Deffert C, Lambeng N, Breville G, Gayet-Ageron A, Lalive P, Toutous Trellu L, Fontao L. Intrathecal Synthesis Index of Specific Anti-Treponema IgG: a New Tool for the Diagnosis of Neurosyphilis. Microbiol Spectr. 2022 Feb 23;10(1):e0147721. doi: 10.1128/spectrum.01477-21. Epub 2022 Feb 9.
PubMed 35138118
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Retro-prospective Multicentric Study Aiming to Evaluate the Benefit of Measuring an Intrathecal Synthesis Index of Specific Antitreponema IgG for Patients Suspected of Neurosyphilis
- ClinicalTrials.gov ID
- NCT06152393
- Acronym / sponsor ID
- Study 2019-00232
- Conditions
- Neurosyphilis
- Keywords
- Neurosyphilis, Treponema pallidum, Intrathecal synthesis, Specific anti-Treponema IgG, Otosyphilis, Ocular syphilis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 181 participants (actual)
- Lead sponsor
- University Hospital, GenevaUniversity, hospital or other
- Collaborators
- Swiss HIV Cohort Study, Swiss National Science Foundation
- Study start
- 1 Mar 2019 (actual)
- Primary completion
- 31 Dec 2022 (actual)
- Study completion
- 31 Dec 2022 (actual)
- First posted
- 30 Nov 2023 (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.
A retro-prospective case-control Swiss study was conducted to evaluate the diagnostic performance of measuring an antibody index (AI) for intrathecal synthesis of specific anti-Treponema pallidum (T. pallidum) IgG for the diagnosis of neurosyphilis.
Detailed description
The diagnosis of neurosyphilis (NS) lacks a true "gold standard" which makes the diagnosis challenging while consequences of a misdiagnosis are potentially severe. The aim of this study was to evaluate the diagnostic performance of measuring an antibody index (AI) for intrathecal synthesis of specific anti-Treponema pallidum (T. pallidum) IgG for the diagnosis of NS.
CSF parameters were analysed and specific anti-T. pallidum IgG were measured simultaneously on paired cerebrospinal fluid (CSF)-serum samples collected between 2007 and 2022 from patients suspected of NS, in Switzerland. An AI was calculated to consider blood-brain barrier integrity. Two NS definitions were used: NS1 included patients with suspicion of NS presenting neurological symptoms and/or acute neuro-sensory signs and positive TPHA/TPPA serology and CSF-TPHA/TPPA≥320, and either CSF-leucocytes >5cells/mm3 and/or CSF-protein >0,45g/l and/or a reactive CSF-VDRL/RPR test. NS2 included patients with NS suspicion presenting acute ocular and/or otologic symptoms, and positive TPHA/TPPA serology, and a favourable response to NS treatment. Controls were patients diagnosed with any other CNS pathologies and with positive TPHA/TPPA serology.
Study design
- Observational model
- Case-control
- Time perspective
- Other
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Control patients | – | Diagnostic Test: Measure of an antibody index for intrathecal synthesis of specific anti-Treponema pallidum IgG by ELISA.Controls were patients diagnosed with TPHA/TPPA serology ≥80 and neurological symptoms requiring a lumbar puncture. |
| NS1 patients | – | Diagnostic Test: Measure of an antibody index for intrathecal synthesis of specific anti-Treponema pallidum IgG by ELISA.NS1 includes: 1) neurological symptoms suggestive of central nervous system (CNS) involvement or acute ophthalmological or acute auditory signs consistent with neurosyhilis (NS), or syphilis with treatment serological failure (< fourfold decrease in the antibody titer of RPR/VDRL 12 months after treatment), and 2) a TPHA/TPPA serology ≥ 80 and a CSF-TPHA/TPPA test ≥ 320, and 3) either CSF-WBC > 5 cells/mm3, and/or CSF-protein > 0,45g/l in the absence of other known causes of these abnormalities, and/or a reactive CSF-VDRL/RPR test, and 4) no differential diagnosis. |
| NS2 patients | – | Diagnostic Test: Measure of an antibody index for intrathecal synthesis of specific anti-Treponema pallidum IgG by ELISA.NS2 includes:1) acute ocular symptoms (recent and sudden decrease in visual acuity) and/or acute otologic dysfunctions (sudden hearing loss, acute tinnitus or vertigo) without other known diagnosis for these clinical abnormalities, 2) and a TPHA/TPPA serology ≥ 80, 3) and a response to NS treatment assessed by ophthalmologic or hearing tests and at least a fourfold reduction of RPR/VDRL titer in blood after 12 months following treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- This is a bidirectional retrospective and prospective multicenter study, including all the patients presenting neurological and neuro-sensory signs (ophthalmic and auditory), for whom we have serum and cerebrospinal fluid samples, from the University Hospitals of Geneva, Zurich and Lausanne, at the ADMED Microbiology Laboratory of La Chaux-de-Fonds and in SHCS centers.
Key inclusion criteria (2 listed)
- All patients who have serum / CSF sample pairs collected concomitantly (3 days maximum interval between blood test and lumbar puncture).
- Age > or = 18 years old.
Key exclusion criteria (3 listed)
- All patients for whom the stored samples do not meet the needs of the diagnostic study, or whose serum and CSF collection date is more than 3 consecutive days.
- Age < 18 years old.
- No written consent form for the prospective part.
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 |
|---|---|---|
| Measure of an antibody index for intrathecal synthesis of specific anti-Treponema pallidum IgG by ELISA.Paired CSF/serum samples from all patients were blind tested for anti-T. pallidum IgG with an ELISA containing recombinant T. pallidum proteins (Euroimmun). The AI was calculated conforming to Reiber's method (PMID 11239944) and as previously described in Alberto et al. (PMID 35138118). | Diagnostic test | Control patients, NS1 patients, NS2 patients |
Primary outcome
Evaluation of the diagnostic performance of measuring an antibody index (AI) for intrathecal synthesis of specific anti-Treponema pallidum IgG for the diagnosis of neurosyphilis.
Time frame: 2020-2022 with retrospective samples from 2007 to 2019 and prospective samples from 2019 to 2022.
AI testing measured with an Elisa specific for anti-Treponema pallidum IgG for all patients : number of patients with positive AI, sensitivity/specificity of the test, and positive/negative predictive values of AI test were estimated.
1 secondary outcome
Intrathecal oligoclonal IgG production analysis
Time frame: 2020-2022 with retrospective samples from 2007 to 2019 and prospective samples from 2019 to 2022.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Nov 2023.
- Background: PubMed 11239944Reiber H, Peter JB. Cerebrospinal fluid analysis: disease-related data patterns and evaluation programs. J Neurol Sci. 2001 Mar 1;184(2):101-22. doi: 10.1016/s0022-510x(00)00501-3.
- Background: PubMed 35138118Alberto C, Deffert C, Lambeng N, Breville G, Gayet-Ageron A, Lalive P, Toutous Trellu L, Fontao L. Intrathecal Synthesis Index of Specific Anti-Treponema IgG: a New Tool for the Diagnosis of Neurosyphilis. Microbiol Spectr. 2022 Feb 23;10(1):e0147721. doi: 10.1128/spectrum.01477-21. Epub 2022 Feb 9.
- Individual participant dataSharing planned: No
Related trials for Neurosyphilis
Not yet recruitingPhase 3
Efficacy and Safety of Minocycline Add-on in Patients With Neurosyphilis
Neurosyphilis
RecruitingPhase 2
Evaluating VM100 Nutritional Supplement for Improving Quality of Life in Duchenne Muscular Dystrophy Patients
Duchenne Muscular Dystrophy, Duchenne Disease
RecruitingPhase 2
Vasodilator and Exercise Study for DMD (VASO-REx)
Duchenne Muscular Dystrophy, Duchenne Disease
RecruitingObservational study
Central Nervous System Infections in Denmark
Central Nervous System Infections, Bacterial Meningitis
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.
The record lists no contact. Use the official record to reach the sponsor.
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 Neurosyphilis, run by University Hospital, Geneva at 1 site in Switzerland.
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 3 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: finished, as of the sponsor's last update on 30 Nov 2023. 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 Switzerland. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluation of the diagnostic performance of measuring an antibody index (AI) for intrathecal synthesis of specific anti-Treponema pallidum IgG for the diagnosis of neurosyphilis. (time frame: 2020-2022 with retrospective samples from 2007 to 2019 and prospective samples from 2019 to 2022.). 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 NCT06152393, 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 30 Nov 2023.