Sydenham ChoreaNCT04084977
Dopaminergic Receptors in Sydenham's Chorea
An observational study of Sydenham Chorea and Strep Throat, run by Shaare Zedek Medical Center at 1 site in Israel.
Trial summary
Sydenham's chorea (SC) is a post-streptococcal, neuropsychiatric disorder associated with anti-neuronal antibodies. The investigators demonstrated elevated anti-D1-receptor (D1R) and anti-D2-receptor (D2R) antibodies titers compared to controls using ELISA. Read more about this study
- Who is it for?
- Ages 2 to 40 years
- Conditions the study is for
- Sydenham Chorea, Strep Throat
- What is being tested?
- Antibody detection
- How many people
- 100 participants
- Where
- 1 siteIsrael
- Study dates
- 1 Jul 2016to 30 Dec 2021
- 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 2 to 40 years
- No healthy volunteers
- Child, Adult
Study population: sydenhams chorea according to clinical parameters
Who may be able to join
- sydenham chora OR strep tonsilitiscontrol without strep tonsilitis OR
Who cannot join
- neurological disrder autoimmune disorder
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Sydenham's Chorea: Is There a Link Between Neuropsychiatric Symptoms and Anti-dopamine Receptor Autoantibodies?
Sydenham's chorea (SC) is a post-streptococcal, neuropsychiatric disorder associated with anti-neuronal antibodies. The investigators demonstrated elevated anti-D1-receptor (D1R) and anti-D2-receptor (D2R) antibodies titers compared to controls using ELISA. Similarly, the investigators found antibodies to surface D2R in neuropsychiatric, autoimmune disorders, including SC using cell-based assays. The investigators hypothesize that these autoantibodies cause neuropsychiatric symptoms by inducing intracellular signaling changes resulting in altered dopaminergic neurotransmission. To check this, the investigators will test whether sera from patients with SC alter dopaminergic signaling pathways. The investigators will examine sera from 30 SC patients with active symptoms and 30 age-matched healthy controls. Patients with SC will be assessed for severity of neuropsychiatric symptoms using UFMG Sydenham's Chorea Rating Scale. Controls with evidence of streptococcal infections or autoimmune disorders will be excluded. Sera will be examined for anti-D1R and anti-D2R antibodies. Signaling studies will assess sera impact on 1) calcium/calmodulin-dependent protein kinase II activity in human neuronal cells. 2) dopamine D1/D2 receptors signaling using cAMP assays in transfected cell lines. The investigators will examine the correlation between modified signaling and clinical symptoms.
Read the detailed description
Participants:
The investigators will enroll participants with acute Sydenham's chorea (aSC) and age-matched controls with streptococcal tonsillitis (ST) within the past 4 months and healthy children (HC) with no a history of a strep infection in the past 6 months and negative throat culture. Informed consent will be obtained from participants and/ or parents. Children with SC will be evaluated for SC severity using the USCRS. The investigators will record clinical data regarding gender, age, duration symptoms, and medical treatments. Controls will be examined by referring physician to rule out chorea. Sera samples from all participants will be stored at -70°C and shipped to the microbiology and immunology lab, University of Oklahoma Health Sciences Center (OHSC) on dry ice.
Laboratory testing:
Immunophenotyping for anti-D1R, anti-D2R, anti- LG and anti-tubulin titers and signaling studies will be performed at the OUHSC microbiology and immunology laboratory.
Autoantibody titers. Sera will be assayed for reactivity with the dopamine D1 and D2 receptors (Human dopamine D1 and D2 receptor membrane antigens, Perkin Elmer-Membrane Target Systems) in the direct ELISA and assays which include the ELISA competitive inhibition. Anti- LG and anti-tubulin titers will be tested as well.
Statistical Analysis:
Time will be categorized in order to model non-linear associations among the groups. Means will be compared among groups using an ANOVA model that included main effects for the time, participant diagnosis and the interaction between participant diagnosis and time. Modeling assumptions will be evaluated using residual plots. A natural log transformation of the antibody measure will be used when there was evidence of non-constant variance across the groups. If a significant interaction between time and participant group will be found, time trends will be summarized separately within each participant group. Post-hoc pair-wise comparisons will be made using Tukey's method to control the type I error rate. A two-sided 0.05 alpha level will be used to define statistical significance. Analyses will be performed using SAS (SAS Institute Inc., SAS v9.4, Cary, NC: SAS Institute Inc.).
- Conditions
- Sydenham Chorea, Strep Throat
- Being tested
- Antibody detection
- Medical subject headings
- Chorea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Antibody detectionDiagnostic test
detecting anti bodies against D1, D2 receptor, tubolin Lysoganglioside
| Study group | Role | What they receive |
|---|---|---|
| Sydenam Chorea (SC) | individuals with SC Receives: Diagnostic Test: Antibody detection | |
| tonsilitis | children with tonsilitis in the past 3 months Receives: Diagnostic Test: Antibody detection | |
| control | children wit no tonsilitis Receives: Diagnostic Test: Antibody detection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Antibody titers
titer levels of anti dopamine receptors (anti-D1 and anti-D2) using ELISA (titer levels are expresed as dilutions i.e. 1:400)
Measured: Once at time of initial visit within the first 4 months from onset
UFMG Sydenham's Chorea Rating Scale
the mean value of the 21 item of clinical chorea rating. Ranging from 0 (=none) to 4 (=severe) for each item
Measured: Upon presentation when symptomatic, usually within 4 months of onset
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2019
- Study start1 Jul 2016
- Primary completion30 Dec 2019 (estimated)
- Study completion30 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sydenham ChoreaStudies of the same condition, open and under way.
- 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
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shaare Zedek Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- University of Oklahoma
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04084977
- Sponsor's protocol ID
- 139/14
- Status last verified
- Aug 2019
- First submitted
- 2 Jan 2019
- Last updated
- 10 Sep 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Menendez CM, Zuccolo J, Swedo SE, Reim S, Richmand B, Ben-Pazi H, Kovoor A, Cunningham MW. Dopamine receptor autoantibody signaling in infectious sequelae differentiates movement versus neuropsychiatric disorders. JCI Insight. 2024 Nov 8;9(21):e164762. doi: 10.1172/jci.insight.164762.
PubMed 39325550
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sydenham's Chorea: Is There a Link Between Neuropsychiatric Symptoms and Anti-dopamine Receptor Autoantibodies?
- ClinicalTrials.gov ID
- NCT04084977
- Acronym / sponsor ID
- 139/14
- Conditions
- Sydenham Chorea, Strep Throat
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Shaare Zedek Medical CenterUniversity, hospital or other
- Collaborators
- University of Oklahoma
- Study start
- 1 Jul 2016 (actual)
- Primary completion
- 30 Dec 2019 (estimated)
- Study completion
- 30 Dec 2021 (estimated)
- First posted
- 10 Sep 2019 (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.
Sydenham's chorea (SC) is a post-streptococcal, neuropsychiatric disorder associated with anti-neuronal antibodies. The investigators demonstrated elevated anti-D1-receptor (D1R) and anti-D2-receptor (D2R) antibodies titers compared to controls using ELISA. Similarly, the investigators found antibodies to surface D2R in neuropsychiatric, autoimmune disorders, including SC using cell-based assays. The investigators hypothesize that these autoantibodies cause neuropsychiatric symptoms by inducing intracellular signaling changes resulting in altered dopaminergic neurotransmission. To check this, the investigators will test whether sera from patients with SC alter dopaminergic signaling pathways. The investigators will examine sera from 30 SC patients with active symptoms and 30 age-matched healthy controls. Patients with SC will be assessed for severity of neuropsychiatric symptoms using UFMG Sydenham's Chorea Rating Scale. Controls with evidence of streptococcal infections or autoimmune disorders will be excluded. Sera will be examined for anti-D1R and anti-D2R antibodies. Signaling studies will assess sera impact on 1) calcium/calmodulin-dependent protein kinase II activity in human neuronal cells. 2) dopamine D1/D2 receptors signaling using cAMP assays in transfected cell lines. The investigators will examine the correlation between modified signaling and clinical symptoms.
Detailed description
Participants:
The investigators will enroll participants with acute Sydenham's chorea (aSC) and age-matched controls with streptococcal tonsillitis (ST) within the past 4 months and healthy children (HC) with no a history of a strep infection in the past 6 months and negative throat culture. Informed consent will be obtained from participants and/ or parents. Children with SC will be evaluated for SC severity using the USCRS. The investigators will record clinical data regarding gender, age, duration symptoms, and medical treatments. Controls will be examined by referring physician to rule out chorea. Sera samples from all participants will be stored at -70°C and shipped to the microbiology and immunology lab, University of Oklahoma Health Sciences Center (OHSC) on dry ice.
Laboratory testing:
Immunophenotyping for anti-D1R, anti-D2R, anti- LG and anti-tubulin titers and signaling studies will be performed at the OUHSC microbiology and immunology laboratory.
Autoantibody titers. Sera will be assayed for reactivity with the dopamine D1 and D2 receptors (Human dopamine D1 and D2 receptor membrane antigens, Perkin Elmer-Membrane Target Systems) in the direct ELISA and assays which include the ELISA competitive inhibition. Anti- LG and anti-tubulin titers will be tested as well.
Statistical Analysis:
Time will be categorized in order to model non-linear associations among the groups. Means will be compared among groups using an ANOVA model that included main effects for the time, participant diagnosis and the interaction between participant diagnosis and time. Modeling assumptions will be evaluated using residual plots. A natural log transformation of the antibody measure will be used when there was evidence of non-constant variance across the groups. If a significant interaction between time and participant group will be found, time trends will be summarized separately within each participant group. Post-hoc pair-wise comparisons will be made using Tukey's method to control the type I error rate. A two-sided 0.05 alpha level will be used to define statistical significance. Analyses will be performed using SAS (SAS Institute Inc., SAS v9.4, Cary, NC: SAS Institute Inc.).
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Sydenam Chorea (SC) | – | Diagnostic Test: Antibody detectionindividuals with SC |
| tonsilitis | – | Diagnostic Test: Antibody detectionchildren with tonsilitis in the past 3 months |
| control | – | Diagnostic Test: Antibody detectionchildren wit no tonsilitis |
Who may qualify
- Ages
- 2 to 40 years
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- sydenhams chorea according to clinical parameters
Key inclusion criteria (1 listed)
- sydenham chora OR strep tonsilitiscontrol without strep tonsilitis OR
Key exclusion criteria (1 listed)
- neurological disrder autoimmune disorder
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 |
|---|---|---|
| Antibody detectiondetecting anti bodies against D1, D2 receptor, tubolin Lysoganglioside | Diagnostic test | Sydenam Chorea (SC), control, tonsilitis |
Primary outcome
Antibody titers
Time frame: Once at time of initial visit within the first 4 months from onset
titer levels of anti dopamine receptors (anti-D1 and anti-D2) using ELISA (titer levels are expresed as dilutions i.e. 1:400)
UFMG Sydenham's Chorea Rating Scale
Time frame: Upon presentation when symptomatic, usually within 4 months of onset
the mean value of the 21 item of clinical chorea rating. Ranging from 0 (=none) to 4 (=severe) for each item
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2019.
- Derived from this study: PubMed 39325550Menendez CM, Zuccolo J, Swedo SE, Reim S, Richmand B, Ben-Pazi H, Kovoor A, Cunningham MW. Dopamine receptor autoantibody signaling in infectious sequelae differentiates movement versus neuropsychiatric disorders. JCI Insight. 2024 Nov 8;9(21):e164762. doi: 10.1172/jci.insight.164762.
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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.
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 Sydenham Chorea and Strep Throat, run by Shaare Zedek Medical Center at 1 site in Israel.
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 1 inclusion and 1 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 Sep 2019. 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 Israel. 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?
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?
Antibody titers (time frame: Once at time of initial visit within the first 4 months from onset). 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 NCT04084977, which also lists 1 linked publication.
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 Sep 2019.