Intravenous Immunoglobulin for PANDAS
Condition: Obsessive-Compulsive Disorder; Children; Anxiety Disorder; Autoimmune Disease; PANDAS
MeSH terms: Autoimmune Diseases; Anxiety Disorders; Compulsive Personality Disorder; Obsessive-Compulsive Disorder
Study type: Interventional
Phase: Phase 3

Summary: 
      Background:

      - Some children experience a sudden onset of symptoms similar to those found in
      obsessive-compulsive disorder that may be caused by the body s reaction to an infection with
      streptococcal bacteria, most commonly seen as strep throat or scarlet fever. When the body s
      immune system reacts against brain cells following a streptococcal infection, the condition
      is known as PANDAS (pediatric autoimmune neuropsychiatric disorders associated with
      streptococcal infections). The immune system response can be inactivated by treatment with a
      drug known as intravenous immunoglobulin (IVIG). Because there is insufficient research on
      IVIG s effects on the immune system of children with PANDAS, including whether IVIG is
      helpful in treating obsessive-compulsive symptoms related to PANDAS, researchers are
      interested in examining whether IVIG is an appropriate treatment for PANDAS and its
      associated symptoms.

      Objectives:

      - To test the safety and effectiveness of intravenous immunoglobulin for the treatment of
      obsessive-compulsive disorder in children with PANDAS (pediatric autoimmune neuropsychiatric
      disorder associated with streptococcal infection).

      Eligibility:

      - Children between 4 and 12 years of age who have obsessive-compulsive disorder (with or
      without a tic disorder) with sudden onset of symptoms following Group A streptococcal
      bacterial infections.

      Design:

        -  Participants will be screened by telephone to obtain medical history and other
           information, followed by in-person screening at the National Institutes of Health
           Clinical Center.

        -  Participants will be admitted to the hospital to receive 2 days of infusions of either
           IVIG or a placebo. Frequent blood samples, imaging studies, and other tests will be
           performed during this visit.

        -  Six weeks after the inpatient stay, participants will return for further blood samples
           and other tests. Participants who did not receive the study drug, or who received the
           drug but did not respond to the initial IVIG infusion, will have the option to receive
           IVIG at this time.

        -  Followup visits will take place 3 months and 6 months after the first evaluation,
           followed by yearly follow-ups for 5 additional years.
    

Detailed description: 
      Objective:

      This study is designed to test the safety and efficacy of intravenous immunoglobulin (IVIG)
      for the treatment of obsessive-compulsive disorder (OCD) symptoms in children with PANDAS
      (pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection).

      Study Population:

      Thirty-two male and female children with severe obsessive-compulsive symptoms related to a
      new onset or first recurrence of symptoms consistent with the PANDAS subtype of OCD.

      Design:

      his is a multi-site double-blind placebo-controlled trial. Potential subjects will be
      screened in person at NIMH, and there will be remote video corroboration by a team of
      collaborators at Yale University. Eligible subjects will be admitted to the 1NW pediatrics
      inpatient unit at the Clinical Center for further assessment, randomization, and study drug
      administration according to protocol. Subjects who fail to improve 6 weeks after blinded
      IVIG/placebo administration (1.0 gm/kg/day of IVIG on two consecutive days; total dose 2.0
      gm/kg) will be eligible to receive open-label IVIG.

      Outcome Measures:

        -  Primary: Improvement in obsessions, compulsions, and other neuropsychiatric symptoms.

        -  Exploratory:

             -  Reduction of titers of cross-reactive antibodies (Abs)

             -  Resolution of basal ganglia inflammation (as measured by pre-/post-changes in MRI
                volumetric scans and inflammatory sequences)

             -  Normalization of selected serum and CSF cytokines
    

Intervention name(s): Gamunex Intravenous Immunoglobulin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 2.0 gm/kg total, IV (in the vein), over 2 days; Normal saline, IV (in the vein), over 2 days
Intervention MeSH terms: Immunoglobulins; Immunoglobulins, Intravenous; Antibodies; gamma-Globulins; Rho(D) Immune Globulin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Placebo Controlled; Obsessive-Compulsive Disorder; Children and Adolescents; Intravenous Immunoglobulin; PANDAS