Intravenous Immunoglobulin for PANDAS

Phase 3

Completed

Conditions: PANDAS
Anxiety Disorder
Autoimmune Disease
Obsessive-Compulsive Disorder
Children

Interventions: Drug: Placebo
Drug: Gamunex Intravenous Immunoglobulin

Registration Number: NCT01281969

Lead Sponsor: National Institute of Mental Health (NIMH)

Brief 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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 48

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group B	Placebo	Drug: Placebo Normal saline, IV (in the vein), over 2 day
Group A	Gamunex Intravenous Immunoglobulin	Drug: Gamunex Intravenous Immunoglobulin 2.0 gm/kg total, IV (in the vein), over 2 days

Primary Outcome Measures

Name	Time	Method
Children's Yale-Brown Obsessive Compulsive Scale Total Score	6 weeks	Active IVIG will be significantly superior to sham IVIG in reducing OC symptoms and providing global relief of neuropsychiatric symptomatology. Total score is reported as the sum of all items and has a range of 0-40. Higher scores indicate more severe symptoms.

Secondary Outcome Measures

Name	Time	Method
Clinical Global Impressions Improvement	6 weeks	1=very much improved, 2=much improved, 3=slightly improved, 4=no change, 5=slightly worse, 6=much worse, 7=very much worse
Clinical Responder to Treatment	6 weeks	Defined as a CGI-I score of 1 or 2 ("much" or "very much" improved) and a decrease in CY-BOCS of at least 30%
The Degree of Treatment Response is Expected to Correlate With the Percentage Reduction in Antinuclear Antibody Titers Following IVIG Administration.	Baseline	Non-zero values of antinuclear antibodies are considered "positive" and reflective of an ongoing immune response in the individual. First, the number of participants who were classified at baseline as having "positive" antinuclear antibodies was calculated (see outcome measure data table, which states the number (AKA "count") of participants who had "positive" antinuclear antibodies at baseline). We hypothesized that improvement in the ongoing immune response, and therefore a reduction in antinuclear antibody titers, would mediate the effect of IVIG on OCD symptom improvement. However, because very few participants were classified as "positive" at baseline, it was not appropriate to pursue the original question of whether a decline in antinuclear antibodies (i.e., from "positive" to "negative") was related to symptom improvement.
The Degree of Treatment Response is Also Expected to Correlate With Decreased Inflammation in Specific Regions of the Brain, as Demonstrated by Changes on MRI	3 Months