Preventive Measures for Childhood-Onset Obsessive-Compulsive Disorder and Tic Disorders (PANDAS Subgroup)

A Trial of Prophylaxis for the PANDAS Subgroup

A subgroup of patients with childhood-onset obsessive-compulsive disorder (OCD) and/or tic disorders has been identified who share a common clinical course characterized by dramatic onset and symptom exacerbations following group A beta-hemolytic streptococcal (GABHS) infections. This subgroup is designated by the acronym PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections). There are five clinical characteristics that define the PANDAS subgroup: presence of OCD and/or tic disorder; prepubertal symptom onset; sudden onset or abrupt exacerbations (relapsing-remitting course); association with neurological abnormalities (presence of adventitious movements or motoric hyperactivity during exacerbations); and temporal association between symptom exacerbations and GABHS infections. In this subgroup, periodic exacerbations appear to be triggered by GABHS infections in a manner similar to that of Sydenham's chorea, the neurological variant of rheumatic fever.

Rheumatic fever is a disorder with a presumed post-streptococcal autoimmune etiology. The streptococcal pathogenesis of rheumatic fever is supported by studies that have demonstrated the effectiveness of penicillin prophylaxis in preventing recurrences of this illness. A trial of penicillin prophylaxis in the PANDAS subgroup demonstrated that penicillin was not superior to placebo as prophylaxis against GABHS infections in these children, but this outcome was felt to be secondary to non-compliance with treatment, and there was no decrease in the number of neuropsychiatric symptom exacerbations in this group. In a study comparing azithromycin and penicillin, both drugs were completely effective in preventing streptococcal infections - there were no documented titer elevations during the year-long study period for children taking either penicillin or azithromycin. Comparable reductions in the severity of tics and obsessive-compulsive symptoms were also observed. Thus, penicillin was not performing as an "active placebo" as originally postulated, but rather provided effective prophylaxis against Group A beta-hemolytic streptococcal. Both azithromycin and penicillin appear to be effective in eliminating GABHS infections, and reducing neuropsychiatric symptom severity; thus, between-group differences are negligible. Since increasing the "n" to demonstrate superiority of one prophylactic agent over another would be impractical, we have amended the study design to address two issues:

  1. To determine if antibiotics prophylaxis against GABHS infections is superior to placebo in prolonging periods of remission among children in the PANDAS subgroup.
  2. To determine if antibiotics prophylaxis against GABHS infections is superior to placebo in improving overall symptom severity for obsessive-compulsive symptoms and tics among children in the PANDAS subgroup.

Because penicillin has a narrower therapeutic index and is less expensive than azithromycin, it is the preferable prophylactic agent. Further, penicillin (250 mg orally twice a day) has a long history of providing safe and effective prophylaxis for rheumatic fever and is the first line oral therapy recommended by the American Heart Association. Thus, penicillin has been chosen as the prophylactic antibiotic in the present study. Blister packs are used to increase compliance and to allow for easier documentation of missed doses.

Study Overview

Detailed Description

The purpose of this study is to determine whether penicillin prevents the symptoms of Obsessive-compulsive Disorder (OCD) and tic disorders from recurring in children with

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS).

A subgroup of children with childhood-onset OCD and/or tic disorders share a common clinical course characterized by dramatic onset and symptom exacerbations following scarlet fever or strep. throat infections. Such infections may be prevented by the prophylactic (preventative dose) administration of antibiotics, such as penicillin. This study will determine the effectiveness of penicillin prophylaxis in preventing relapses of OCD and/or tics in the PANDAS subgroup.

Participants receive a comprehensive psychiatric, neurological and physical evaluation. Children will initially receive penicillin tablets, and then will be randomly assigned to receive either penicillin or placebo tablets for 6 months. Children will be monitored monthly by either in-person visits or a telephone interview. Any child who has a significant increase in his or her OCD or tics is taken off the randomized medication and put on open-label penicillin for the rest of the study.

For more information about this study please visit the Official P.A.N.D.A.S. Web Page at the following web address:

http://intramural.nimh.nih.gov/research/pdn/web.htm

Study Type

Interventional

Enrollment

90

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institute of Mental Health (NIMH)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

INCLUSION CRITERIA:

  1. Ages 4 - 18 years
  2. Fulfill criteria for membership in the PANDAS subgroup:

    1. Presence of OCD and/or tic disorder
    2. Prepubertal symptom onset
    3. Abrupt onset and episodic (relapsing-remitting) symptom course
    4. Association between symptom exacerbations and GABHS infections
    5. Presence of choreiform movements or other neurological abnormalities during symptom exacerbations.

Because "time to relapse" is one of the primary outcome variables, children will not be eligible for randomization until their symptoms are in (at least partial) remission. At the time of randomization, symptom severity scores should be less than 50% of the child's previous maximum score on both the CY-BOCS and YGTSS, and no higher than a total score of 20 on the CY-BOCS or 30 on the YGTSS.

EXCLUSION CRITERIA:

  1. Personal history of penicillin allergy
  2. History of rheumatic fever, including Sydenham's chorea
  3. Diagnosis of autism, schizophrenia or other psychotic disorder
  4. Chronic illnesses, particularly neurologic and immunologic disorders

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 1993

Study Completion

January 1, 2006

Study Registration Dates

First Submitted

November 3, 1999

First Submitted That Met QC Criteria

November 3, 1999

First Posted (Estimate)

November 4, 1999

Study Record Updates

Last Update Posted (Estimate)

March 4, 2008

Last Update Submitted That Met QC Criteria

March 3, 2008

Last Verified

January 1, 2006

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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