Pandas | Antibiotic Treatment and Intravenous Immunoglobulin Trial for PANDAS
Pandas research study
What is the primary objective of this study?
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) and/or 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 OCD/tic 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 OCD/tic 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 tissues.(No 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 SSRI+AB 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 SSRI+AB or SSRI+placebo 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 SSRI+AB or SSRI+placebo and in case also after IVIG treatment.
Who is eligible to participate?
Inclusion Criteria: - Ages 4 -40 years - Presence of DSM-IV-R obsessive compulsive disorder or tic disorder and at least two of the following: 1. Anxieties e.g. new onset separation anxiety 2. Sensory abnormalities (tactile/auditory/visual defensiveness or visual misperceptions) 3. Behavioral Regression (e.g. new onset impulsivity, hyperactivity, meltdowns) 4. Deterioration in school performance or in handwriting 5. Emotional lability and/or 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 - Laboratory documentation of infection Exclusion Criteria: - Exclusion criteria for all subjects are: non-tic neurologic disorder, presence of immunologic disorder, presence of serious medical illness, IgA deficiency (< 20mg/dL), hyperviscosity syndromes, psychotropic therapy.
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:Sertraline+Antibiotic (penicillin/azithromycin)12 weeks treatment with a combination of Sertraline (to a maximum of 200 mg/day) and an antibiotic (benzathine penicillin G 1.200.000 U every 3 weeks or, in case of allergy, azithromycin 500 mg/week. Non-responder patients will be treated with IVIG (2g/kg over 5 days for 5 consecutive months)
Drug:Sertraline+placebo12 weeks treatment with a combination of sertraline (to a maximum of 200 mg/day) and placebo
Biological:IVIGPatients who will not respond to SSRI+antibiotic (penicillin/azithromycin) will be treated with IVIG (2g/kg over 5 days for 5 consecutive months)
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
SSRI+ABIntervention: sertraline+antibiotic (penicillin/azithromycin) 12 weeks treatment with a combination of sertraline (to a maximum of 200 mg/day)and one antibiotic ( benzathine penicillin G 1.200.000 U every 3 weeks or, in case of allergy, azithromycin 500 mg/week ). Patients who will not respond to SSRI+antibiotic (penicillin/azithromycin) will be treated with IVIG (2g/kg over 5 days for 5 consecutive months)
SSRI+placeboIntervention: Sertraline+placebo 12 weeks treatment with a combination of sertraline (to a maximum of 200 mg/day) and a placebo
Start Date: June 2013
Completed Date: June 2016
Phase: Phase 2
Primary Outcome: The improvement of OC/tic symptoms will be superior in patients treated with SSRI+AB and in case with IVIG, compared with those treated with SSRI+placebo, as assessed by the YBOCS/YGTSS
Secondary Outcome: The degree of treatment response is expected to correlate with the percentage reduction in antibodies titers following IVIG administration
Study sponsors, principal investigator, and references
Principal Investigator: Stefano Pallanti, MD; PhD
Lead Sponsor: CNS Onlus
Collaborator: University of Florence
Garvey MA, Perlmutter SJ, Allen AJ, Hamburger S, Lougee L, Leonard HL, Witowski ME, Dubbert B, Swedo SE. A pilot study of penicillin prophylaxis for neuropsychiatric exacerbations triggered by streptococcal infections. Biol Psychiatry. 1999 Jun 15;45(12):1564-71.