Antibiotic Treatment and Intravenous Immunoglobulin Trial for PANDAS

NCT01769027 | Withdrawn Phase 2

• 1 other identifier: spallanti
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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) 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.

Conditions

Pandas

Outcome Measures

Primary Outcomes (1)

• 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

  6 months

Secondary Outcomes (2)

• The degree of treatment response is expected to correlate with the percentage reduction in antibodies titers following IVIG administration

  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

  6 months

Study Arms (2)

SSRI+AB

ACTIVE COMPARATOR

Intervention: 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)

Drug: Sertraline+Antibiotic (penicillin/azithromycin); Biological: IVIG

SSRI+placebo

PLACEBO COMPARATOR

Intervention: Sertraline+placebo 12 weeks treatment with a combination of sertraline (to a maximum of 200 mg/day) and a placebo

Drug: Sertraline+placebo

Interventions

Sertraline+Antibiotic (penicillin/azithromycin) DRUG

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)

Also known as: Zoloft, Lustral, Bicillin L-A, Permapen, Zythromax

SSRI+AB

Sertraline+placebo DRUG

12 weeks treatment with a combination of sertraline (to a maximum of 200 mg/day) and placebo

Also known as: Zoloft, Lustral

SSRI+placebo

IVIG BIOLOGICAL

Patients who will not respond to SSRI+antibiotic (penicillin/azithromycin) will be treated with IVIG (2g/kg over 5 days for 5 consecutive months)

Also known as: Gamimune N, Gammagard

SSRI+AB

Eligibility Criteria

• Age: 4 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Ages 4 -40 years
• Presence of DSM-IV-R obsessive compulsive disorder or tic disorder and at least two of the following:
• Anxieties e.g. new onset separation anxiety
• Sensory abnormalities (tactile/auditory/visual defensiveness or visual misperceptions)
• Behavioral Regression (e.g. new onset impulsivity, hyperactivity, meltdowns)
• Deterioration in school performance or in handwriting
• Emotional lability and/or depression
• Urinary symptoms (frequent urination or enuresis)
• Sleep disturbances
• Anorexia
• Sudden onset of symptoms or episodic course of symptom severity following infections
• Laboratory documentation of infection

Sponsors & Collaborators

• CNS Onlus: lead
• University of Florence: collaborator

Related Publications (4)

• 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. doi: 10.1016/s0006-3223(99)00020-7.

  PMID: 10376116 BACKGROUND

• Perlmutter SJ, Leitman SF, Garvey MA, Hamburger S, Feldman E, Leonard HL, Swedo SE. Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood. Lancet. 1999 Oct 2;354(9185):1153-8. doi: 10.1016/S0140-6736(98)12297-3.

  PMID: 10513708 BACKGROUND

• Snider LA, Lougee L, Slattery M, Grant P, Swedo SE. Antibiotic prophylaxis with azithromycin or penicillin for childhood-onset neuropsychiatric disorders. Biol Psychiatry. 2005 Apr 1;57(7):788-92. doi: 10.1016/j.biopsych.2004.12.035.

  PMID: 15820236 BACKGROUND

• Swedo SE, Leonard HL, Garvey M, Mittleman B, Allen AJ, Perlmutter S, Lougee L, Dow S, Zamkoff J, Dubbert BK. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry. 1998 Feb;155(2):264-71. doi: 10.1176/ajp.155.2.264.

  PMID: 9464208 BACKGROUND

MeSH Terms

Conditions

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections

Interventions

Penicillins; Azithromycin; Sertraline; Penicillin G Benzathine; Immunoglobulins, Intravenous

Intervention Hierarchy (Ancestors)

beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones; 1-Naphthylamine; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Penicillin G; Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Stefano Pallanti, MD; PhD

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: December 14, 2012
• First Posted: January 16, 2013
• Study Start: June 1, 2013
• Primary Completion: December 1, 2013
• Study Completion: June 1, 2016
• Last Updated: February 21, 2023

Record last verified: 2023-02