Antibiotic Treatment and Intravenous Immunoglobulin Trial for PANDAS (ATIVPANDAS)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified January 2013 by CNS Onlus
Sponsor:
Collaborator:
University of Florence
Information provided by (Responsible Party):
Stefano Pallanti, CNS Onlus
ClinicalTrials.gov Identifier:
NCT01769027
First received: December 14, 2012
Last updated: January 15, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Pandas
Drug: Sertraline+Antibiotic (penicillin/azithromycin)
Drug: Sertraline+placebo
Biological: IVIG
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Antibiotic Treatment and Intravenous Immunoglobulin Double-blind, Randomized, Placebo-controlled Trial for PANDAS

Resource links provided by NLM:


Further study details as provided by CNS Onlus:

Primary Outcome Measures:
  • 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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]

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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: June 2013
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: SSRI+AB
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)

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)

Other Names:
  • Zoloft
  • Lustral
  • Bicillin L-A
  • Permapen
  • Zythromax
Biological: IVIG
Patients who will not respond to SSRI+antibiotic (penicillin/azithromycin) will be treated with IVIG (2g/kg over 5 days for 5 consecutive months)
Other Names:
  • Gamimune N
  • Gammagard
Placebo Comparator: SSRI+placebo
Intervention: Sertraline+placebo 12 weeks treatment with a combination of sertraline (to a maximum of 200 mg/day) and a placebo
Drug: Sertraline+placebo
12 weeks treatment with a combination of sertraline (to a maximum of 200 mg/day) and placebo
Other Names:
  • Zoloft
  • Lustral

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 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.
  • Symptoms are of moderate severity with Yale-Brown Obsessive Compulsive Scale (Y-BOCS) (or with the children's version for subjects below 16 years of age) of more or equal to 16 and/or 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 (< 20mg/dL), hyperviscosity syndromes, psychotropic therapy.

Interventions:

All patients will be treated with sertraline (to a maximum of 200 mg/day. This study will involve a 12 week double-blind, placebo-controlled, randomized trial with benzathine penicillin G (1.200.000 U every 3 weeks) or azithromycin (500 mg/week) in case of penicillin allergy. Non-responders patients will be treated with IVIG (2 g/kg of body weight over 5 days, for 5 consecutive months)

Outcomes:

Primary Outcome Measures:

  • Significant reduction of OC/tic symptoms severity, as assessed by YBOCS/YGTSS, compared to placebo, after antibiotic prophylaxis. [ Time Frame: 6 months ]
  • Significant reduction of OC/tic symptoms severity, as assessed by YBOCS/YGTSS, 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.
  Eligibility

Ages Eligible for Study:   4 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01769027

Contacts
Contact: Stefano Pallanti, MD, PhD +390557949707 stefanopallanti@yahoo.it

Sponsors and Collaborators
CNS Onlus
University of Florence
Investigators
Principal Investigator: Stefano Pallanti, MD; PhD
  More Information

Publications:
Responsible Party: Stefano Pallanti, Associate Professor, CNS Onlus
ClinicalTrials.gov Identifier: NCT01769027     History of Changes
Other Study ID Numbers: spallanti
Study First Received: December 14, 2012
Last Updated: January 15, 2013
Health Authority: Italy: Ethics Committee

Additional relevant MeSH terms:
Anti-Bacterial Agents
Penicillin G
Penicillin G Benzathine
Penicillin G Procaine
Azithromycin
Antibiotics, Antitubercular
Immunoglobulins
Antibodies
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Sertraline
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents
Immunologic Factors
Physiological Effects of Drugs
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents

ClinicalTrials.gov processed this record on July 26, 2014