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Intravenous Immunoglobulin for PANDAS

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01281969
Recruitment Status : Completed
First Posted : January 24, 2011
Results First Posted : March 17, 2020
Last Update Posted : March 17, 2020
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )

Brief Summary:


- 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.


- 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).


- 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.


  • 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.

Condition or disease Intervention/treatment Phase
Obsessive-Compulsive Disorder Children Anxiety Disorder Autoimmune Disease PANDAS Drug: Gamunex Intravenous Immunoglobulin Drug: Placebo Phase 3

Detailed Description:


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.


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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Placebo-Controlled Trial of Intravenous Immunoglobulin (IVIG) for PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections)
Study Start Date : January 2011
Actual Primary Completion Date : December 2015
Actual Study Completion Date : August 13, 2018

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Group A
Drug: Gamunex Intravenous Immunoglobulin 2.0 gm/kg total, IV (in the vein), over 2 days
Drug: Gamunex Intravenous Immunoglobulin
2.0 gm/kg total, IV (in the vein), over 2 days

Placebo Comparator: Group B
Drug: Placebo Normal saline, IV (in the vein), over 2 day
Drug: Placebo
Normal saline, IV (in the vein), over 2 days

Primary Outcome Measures :
  1. Children's Yale-Brown Obsessive Compulsive Scale Total Score [ Time Frame: 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 :
  1. Clinical Global Impressions Improvement [ Time Frame: 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

  2. Clinical Responder to Treatment [ Time Frame: 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%

  3. The Degree of Treatment Response is Expected to Correlate With the Percentage Reduction in Antinuclear Antibody Titers Following IVIG Administration. [ Time Frame: 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.

  4. 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 [ Time Frame: 3 Months ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   4 Years to 13 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Male and female children 4-13 years of age.

Presence of (Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision) DSM-IV TR OCD with or without a tic disorder.

Moderate or greater severity of symptoms, with a score of greater than or equal to 20 on the Children s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) and greater than or equal to 4 on the Clinical Global Impression Severity scale (CGI-S).

The acute onset within the previous six months of symptoms in a child previously well, or the first acute recurrence within the previous six months, after a period of relatively complete remission of symptoms. The acuity of symptom onset/exacerbation is key and must be severe, dramatic in onset, and proceed from no/minimal symptoms to maximum severity within 24-48 hours.

Symptom onset or first exacerbation preceded within four months by a GAS infection, as documented by positive throat culture, exposure to documented GAS infection (in a close contact, such as a sibling sharing a bedroom), and/or documented two-fold rise in one or more anti-GAS antibody titers such as anti-streptolysin O, anti-streptococcal DNAaseB, anti-carbohydrate antibodies and others.

Onset/exacerbation of OCD is accompanied by at least three of the following 7 clinical signs and symptoms. The acuity of the comorbid symptoms must be similar to the OCD symptoms and occur in the same time interval.

  1. Markedly increased level of anxiety, particularly new onset of separation anxiety.
  2. Emotional lability, irritability, aggressive behavior and/or personality change.
  3. Sudden difficulties with concentration or learning.
  4. Developmental regression ("baby-talk," temper tantrums; behaviors atypical for actual chronological age).
  5. Sleep disorder (insomnia, night terrors, refusal to sleep alone).
  6. Handwriting deterioration or other sign of motoric dysfunction (including new onset of motor hyperactivity, or presence of choreiform finger movements).
  7. Urinary frequency or increased urge to urinate; daytime or night-time secondary enuresis.


History of rheumatic fever, including Sydenham chorea (the neurologic manifestation).

Presence of symptoms consistent with autism, schizophrenia, or other psychotic disorder (unless psychotic symptoms have onset coincident with the possible PANDAS and are attributed to OCD).

Presence of a neurological disorder other than a tic disorder.

IQ <70. Child subjects need to be able to contribute meaningfully to baseline and follow-up ratings, to report adverse effects, and to assent to participation.

Presence of serious or unstable medical illness or psychiatric or behavioral symptoms that would make participation unsafe or study procedures too difficult to tolerate.

IgA deficiency (<20mg/dL). Intravenous immunoglobulin may contain trace IgA, which may very rarely lead to life-threatening anaphylaxis in IgA-deficient participants with anti-IgA antibodies (Misbah 1993).

Hyperviscosity syndromes, which can increase risks associated with IVIG administration.

Need for live virus vaccine within six months after receiving IVIG (which may be 7.5 months from randomization) since IVIG can interfere with effectiveness of such vaccines. IVIG should not be administered sooner than two weeks after administration of a live virus vaccine, for the same reason.

Taking nephrotoxic drugs. Every concomitant medication will be subject to scrutiny and possible consultation with pediatric safety monitors before randomization to study drug. See below as well.

Recent (less than eight weeks) initiation of cognitive-behavior therapy (CBT).

Recent (less than eight weeks) initiation or change in dosage of psychotropic medication for OCD or tic disorder (e.g., serotonin reuptake inhibitors for OCD, alpha-2 agonists or antipsychotics for tic disorders).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01281969

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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Mental Health (NIMH)
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Principal Investigator: Susan E Swedo, M.D. National Institute of Mental Health (NIMH)
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: National Institute of Mental Health (NIMH) Identifier: NCT01281969    
Other Study ID Numbers: 110058
11-M-0058 ( Other Identifier: National Institute of Mental Health )
First Posted: January 24, 2011    Key Record Dates
Results First Posted: March 17, 2020
Last Update Posted: March 17, 2020
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) ):
Placebo Controlled
Obsessive-Compulsive Disorder
Children and Adolescents
Intravenous Immunoglobulin
Additional relevant MeSH terms:
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Autoimmune Diseases
Anxiety Disorders
Compulsive Personality Disorder
Obsessive-Compulsive Disorder
Pathologic Processes
Mental Disorders
Personality Disorders
Immune System Diseases
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Immunologic Factors
Physiological Effects of Drugs