Ignite Creation Date:
2024-05-06 @ 1:16 AM
Last Modification Date:
2024-10-26 @ 11:01 AM
Study NCT ID:
NCT01769027
Status:
WITHDRAWN
Last Update Posted:
2023-02-21
First Post:
2012-12-14
Brief Title:
Antibiotic Treatment and Intravenous Immunoglobulin Trial for PANDAS
Sponsor:
CNS Onlus
Organization:
CNS Onlus
Study Overview
Official Title:
Antibiotic Treatment and Intravenous Immunoglobulin Double-blind Randomized Placebo-controlled Trial for PANDAS
Status:
WITHDRAWN
Status Verified Date:
2023-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
No participants enrolled
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ATIVPANDAS
Brief Summary:
An increasing body of evidence indicates that an immune basis might underline a number of pediatric neuropsychiatric disorders Research studies found a subgroup of children who had Obsessive compulsive OCD andor tic disorders following a Group A beta-hemolytic streptococcal GAS infection The subgroup is identified by the acronym PANDAS pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections More recently several PANDAS variants have been described including adult-onset variant There are many evidences that OCDtic symptoms could be due to an immunologic reaction against brain tissues following a streptococcal infection
The purpose of this study is to know if sertraline one of the SSRI approved by FDA to improve OCDtic symptoms in these patients plus antibiotic benzathine penicillin G or azithromycin in case of penicillin allergy is more effective than SSRI only
Patients who will not respond to antibiotic will be treated with intravenous immunoglobulin IVIG in order to inactivate the immune reaction versus brain tissuesNo treatment response is based on the lack of a Y-BOCS score improvement of at least 35
Objectives
To determine the safety and efficacy of SSRIAB compared to SSRI only
To test the safety and additional beneficial effects of high dose of IVIG on antibiotic prophylaxis for the treatment of OCD symptoms in non-responders patients with PANDAS
Study methodology
Participants will be screened to obtain medical history and other information at Neurologic and Psychiatric Sciences Department of Florence University Hospital and at Paris-est University
Participants will receive a treatment of either SSRIAB or SSRIplacebo for 12 weeks double-blind randomized trial
Patients who will not respond to AB will be admitted to the hospital to receive IVIG for 5 days for 5 consecutive months
Follow-up visits will take place 3 and 6 months after the first evaluation followed by 6 months follow-ups for 3 additional years
Blood samples including blood cytokine determination ECG Doppler and 2-dimensional echocardiogram EEG imaging studies 2 tesla MRI and other tests will be performed both before and after the treatment with SSRIAB or SSRIplacebo and in case also after IVIG treatment
The purpose of this study is to know if sertraline one of the SSRI approved by FDA to improve OCDtic symptoms in these patients plus antibiotic benzathine penicillin G or azithromycin in case of penicillin allergy is more effective than SSRI only
Patients who will not respond to antibiotic will be treated with intravenous immunoglobulin IVIG in order to inactivate the immune reaction versus brain tissuesNo treatment response is based on the lack of a Y-BOCS score improvement of at least 35
Objectives
To determine the safety and efficacy of SSRIAB compared to SSRI only
To test the safety and additional beneficial effects of high dose of IVIG on antibiotic prophylaxis for the treatment of OCD symptoms in non-responders patients with PANDAS
Study methodology
Participants will be screened to obtain medical history and other information at Neurologic and Psychiatric Sciences Department of Florence University Hospital and at Paris-est University
Participants will receive a treatment of either SSRIAB or SSRIplacebo for 12 weeks double-blind randomized trial
Patients who will not respond to AB will be admitted to the hospital to receive IVIG for 5 days for 5 consecutive months
Follow-up visits will take place 3 and 6 months after the first evaluation followed by 6 months follow-ups for 3 additional years
Blood samples including blood cytokine determination ECG Doppler and 2-dimensional echocardiogram EEG imaging studies 2 tesla MRI and other tests will be performed both before and after the treatment with SSRIAB or SSRIplacebo and in case also after IVIG treatment
Detailed Description:
Inclusion criteria for PANDAS subjects are
Ages 4 -40 years
Presence of DSM-IV-R obsessive compulsive disorder or tic disorder and at least two of the following
1 Anxieties eg new onset separation anxiety
2 Sensory abnormalities tactileauditoryvisual defensiveness or visual misperceptions
3 Behavioral Regression eg new onset impulsivity hyperactivity meltdowns
4 Deterioration in school performance or in handwriting
5 Emotional lability andor depression
6 Urinary symptoms frequent urination or enuresis
7 Sleep disturbances
8 Anorexia
Sudden onset of symptoms or episodic course of symptom severity following infections
Symptoms are of moderate severity with Yale-Brown Obsessive Compulsive Scale Y-BOCS or with the childrens version for subjects below 16 years of age of more or equal to 16 andor Yale Global Tic Severity Scale YGTSS of more or equal to 21 and with significant impairment CGI of moderate or worse
Laboratory documentation of infection as documented by at least two of these positive throat culture documented rise in one or more anti-GAS antibody titers such as anti-streptolysin O anti-streptococcal DNAaseB
Exclusion criteria for all subjects are non-tic neurologic disorder presence of immunologic disorder presence of serious medical illness IgA deficiency 20mgdL hyperviscosity syndromes psychotropic therapy
Interventions
All patients will be treated with sertraline to a maximum of 200 mgday This study will involve a 12 week double-blind placebo-controlled randomized trial with benzathine penicillin G 1200000 U every 3 weeks or azithromycin 500 mgweek in case of penicillin allergy Non-responders patients will be treated with IVIG 2 gkg of body weight over 5 days for 5 consecutive months
Outcomes
Primary Outcome Measures
Significant reduction of OCtic symptoms severity as assessed by YBOCSYGTSS compared to placebo after antibiotic prophylaxis Time Frame 6 months
Significant reduction of OCtic symptoms severity as assessed by YBOCSYGTSS compared to placebo after IVIG treatment Time Frame 6 months
Secondary Outcome Measures
The degree of treatment response is expected to correlate with the percentage reduction in antibodies titers following IVIG administration Time Frame 6 months
The degree of treatment response is also expected to correlate with decreased inflammation in specific regions of the brain as demonstrated by macroscopic changes and microstructural alterations on MRI and serum and CSF cytokines and chemokines Time Frame 6 months
Expected impact
To clarify the utility of antibiotic and IVIG therapy in PANDAS and how the IVIG produce their effects
To individualize the treatment
To disseminate new data for the treatment of PANDAS
Ages 4 -40 years
Presence of DSM-IV-R obsessive compulsive disorder or tic disorder and at least two of the following
1 Anxieties eg new onset separation anxiety
2 Sensory abnormalities tactileauditoryvisual defensiveness or visual misperceptions
3 Behavioral Regression eg new onset impulsivity hyperactivity meltdowns
4 Deterioration in school performance or in handwriting
5 Emotional lability andor depression
6 Urinary symptoms frequent urination or enuresis
7 Sleep disturbances
8 Anorexia
Sudden onset of symptoms or episodic course of symptom severity following infections
Symptoms are of moderate severity with Yale-Brown Obsessive Compulsive Scale Y-BOCS or with the childrens version for subjects below 16 years of age of more or equal to 16 andor Yale Global Tic Severity Scale YGTSS of more or equal to 21 and with significant impairment CGI of moderate or worse
Laboratory documentation of infection as documented by at least two of these positive throat culture documented rise in one or more anti-GAS antibody titers such as anti-streptolysin O anti-streptococcal DNAaseB
Exclusion criteria for all subjects are non-tic neurologic disorder presence of immunologic disorder presence of serious medical illness IgA deficiency 20mgdL hyperviscosity syndromes psychotropic therapy
Interventions
All patients will be treated with sertraline to a maximum of 200 mgday This study will involve a 12 week double-blind placebo-controlled randomized trial with benzathine penicillin G 1200000 U every 3 weeks or azithromycin 500 mgweek in case of penicillin allergy Non-responders patients will be treated with IVIG 2 gkg of body weight over 5 days for 5 consecutive months
Outcomes
Primary Outcome Measures
Significant reduction of OCtic symptoms severity as assessed by YBOCSYGTSS compared to placebo after antibiotic prophylaxis Time Frame 6 months
Significant reduction of OCtic symptoms severity as assessed by YBOCSYGTSS compared to placebo after IVIG treatment Time Frame 6 months
Secondary Outcome Measures
The degree of treatment response is expected to correlate with the percentage reduction in antibodies titers following IVIG administration Time Frame 6 months
The degree of treatment response is also expected to correlate with decreased inflammation in specific regions of the brain as demonstrated by macroscopic changes and microstructural alterations on MRI and serum and CSF cytokines and chemokines Time Frame 6 months
Expected impact
To clarify the utility of antibiotic and IVIG therapy in PANDAS and how the IVIG produce their effects
To individualize the treatment
To disseminate new data for the treatment of PANDAS
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None