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Dopaminergic Receptors in Sydenham's Chorea

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT04084977
Recruitment Status : Enrolling by invitation
First Posted : September 10, 2019
Last Update Posted : September 10, 2019
University of Oklahoma
Information provided by (Responsible Party):
Shaare Zedek Medical Center

Brief 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. 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.

Condition or disease Intervention/treatment
Sydenham Chorea Strep Throat Diagnostic Test: Antibody detection

Detailed Description:


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.).

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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Case-Control
Time Perspective: Retrospective
Official Title: Sydenham's Chorea: Is There a Link Between Neuropsychiatric Symptoms and Anti-dopamine Receptor Autoantibodies?
Actual Study Start Date : July 1, 2016
Estimated Primary Completion Date : December 30, 2019
Estimated Study Completion Date : December 30, 2021

Group/Cohort Intervention/treatment
Sydenam Chorea (SC)
individuals with SC
Diagnostic Test: Antibody detection
detecting anti bodies against D1, D2 receptor, tubolin Lysoganglioside

children with tonsilitis in the past 3 months
Diagnostic Test: Antibody detection
detecting anti bodies against D1, D2 receptor, tubolin Lysoganglioside

children wit no tonsilitis
Diagnostic Test: Antibody detection
detecting anti bodies against D1, D2 receptor, tubolin Lysoganglioside

Primary Outcome Measures :
  1. 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)

  2. 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

Biospecimen Retention:   Samples Without DNA

Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 40 Years   (Child, Adult)
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
sydenhams chorea according to clinical parameters

Inclusion Criteria:

  • sydenham chora OR strep tonsilitiscontrol without strep tonsilitis OR

Exclusion Criteria:

  • neurological disrder autoimmune disorder

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04084977

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Shaare Zedek Medical center
Jerusalem, Israel, 91031
Sponsors and Collaborators
Shaare Zedek Medical Center
University of Oklahoma

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Responsible Party: Shaare Zedek Medical Center Identifier: NCT04084977     History of Changes
Other Study ID Numbers: 139/14
First Posted: September 10, 2019    Key Record Dates
Last Update Posted: September 10, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Movement Disorders
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Immunologic Factors
Physiological Effects of Drugs