Antibiotic Treatment Trial for the PANDAS/PANS Phenotype
Condition: PANS; PANDAS; Obsessive Compulsive Disorder (OCD)
MeSH terms: Obsessive-Compulsive Disorder
Intervention: Azithromycin; Placebo
Intervention description: Antibiotic used to treat infections; Thickening compound with sugar and flavoring
Intervention MeSH terms: Azithromycin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 47.0
Sex: All
Minimum age: 4 Years
Maximum age: 14 Years
Healthy volunteers: No
Keywords: PANS; PANDAS; OCD; Tics; Azithromycin; Antibiotic Treatment

Summary:

      The purpose of this research study is to know if the antibiotic azithromycin, an antibiotic
      approved by the U.S. Food and Drug Administration (FDA) for treating infections, improves
      symptom severity in children with sudden and severe onset obsessive compulsive symptoms known
      as PANS, Pediatric Acute Onset Neuropsychiatric Syndrome, and PANDAS, Pediatric Autoimmune
      Neuropsychiatric Disorder Associated with Streptococcus. This study seeks to compare the
      effects of placebo vs. azithromycin on Obsessive Compulsive Disorder (OCD) symptom severity
      as well as to assess immune risk factors in children with PANDAS/PANS. Obsessions are
      repetitive, unwanted thoughts or worries that may be unpleasant, silly, or embarrassing.
      Compulsions are repetitive or ritualistic actions that are performed to ease anxiety or
      worries. Doctors think these symptoms may be caused or exacerbated by certain infections such
      as Streptococcus pyogenes, Mycoplasma pneumonia, Borrelia burgordfi, etc. These infections
      commonly cause strep throat, walking pneumonia, and Lyme Disease, among others.

      This study will involve a 4 week double-blind, placebo-controlled randomized trial of
      azithromycin (Double Blind Phase). At the end of this 4 week trial, the child will be
      assigned to azithromycin for 8 weeks (Open Label Phase). At the end of these 12 weeks, a
      Naturalistic Observation phase will assess the child's symptom characteristics for up to 40
      weeks.

      The study hypothesizes that children receiving antibiotic will show significantly greater
      overall improvement in severity compared with placebo, and that children with sudden onset of
      OCD and whose subsequent course shows dramatic fluctuations will have evidence of immune risk
      factors that predisposes to this presentation.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Ages 4 -14 years.

          -  Presence of OCD 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 Anorexia

          -  Current episode OCD of recent onset (less or equal to 6 months) associated with
             infection

          -  Symptom onset appears temporally related to infection or exposure

          -  Symptoms are of moderate severity with significant impairment (CGI of moderate or
             worse) and CY-BOCS of more or equal to 16.

          -  Parental willingness to accompany their child for multiple study visits and be
             responsible for medication compliance.

        Exclusion Criteria:

          -  History of Rheumatic Fever including Sydenham's Chorea (heart murmur, frank chorea,
             EKG PR or QTc prolongation, abnormal reflexes (Gordon-Hey reflex)).

          -  Diagnosis of autism (moderate - severe), schizophrenia, mental retardation or chronic
             degenerative neurological disease.

          -  Any illness for which antibiotic treatment may be contraindicated (e.g. Liver
             disease).

          -  Personal history of adverse reaction or allergy to azithromycin.

          -  Recent or planned psychopharmacologic (4 weeks for most medications or 8 weeks for
             SSRIs) treatment changes.

          -  Antibiotic prophylaxis therapy or history of neuropsychiatric non-response to prior
             antibiotic trial.

          -  Currently participating in cognitive behavioral therapy or habit reversal therapy for
             OCD and/or tics.

          -  Weight less than 15 kilograms

          -  Concurrent therapy with medications that may increase adverse effects (eg. pimozide,
             citalopram, tricyclic antidepressants, etc).