Ignite Creation Date:
2024-05-06 @ 1:38 PM
Last Modification Date:
2024-10-26 @ 1:17 PM
Study NCT ID:
NCT04084977
Status:
UNKNOWN
Last Update Posted:
2019-09-10
First Post:
2019-01-02
Brief Title:
Dopaminergic Receptors in Sydenhams Chorea
Sponsor:
Shaare Zedek Medical Center
Organization:
Shaare Zedek Medical Center
Study Overview
Official Title:
Sydenhams Chorea Is There a Link Between Neuropsychiatric Symptoms and Anti-dopamine Receptor Autoantibodies
Status:
UNKNOWN
Status Verified Date:
2019-08
Last Known Status:
ENROLLING_BY_INVITATION
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Sydenhams 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 Sydenhams 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 calciumcalmodulin-dependent protein kinase II activity in human neuronal cells 2 dopamine D1D2 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 Sydenhams 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 -70C 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 Tukeys method to control the type I error rate A two-sided 005 alpha level will be used to define statistical significance Analyses will be performed using SAS SAS Institute Inc SAS v94 Cary NC SAS Institute Inc
The investigators will enroll participants with acute Sydenhams 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 -70C 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 Tukeys method to control the type I error rate A two-sided 005 alpha level will be used to define statistical significance Analyses will be performed using SAS SAS Institute Inc SAS v94 Cary NC SAS Institute Inc
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None