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

NCT00001359 | Completed Phase 2

• 2 other identifiers: 93012293-M-0122
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

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. 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. 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.

Conditions

Mental Disorder Diagnosed in Childhood; Obsessive Compulsive Disorder; Streptococcal Infection; Tic Disorder

Keywords

Obsessive Compulsive Disorder; PANDAS Associated with Streptococcal Infections; Adolescents; Autoimmune Illness; Children; Tic Disorders; Streptococcal Infections; Childhood Onset Neuropsychiatric Disorder

Interventions

Penicillin or Placebo DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages 4 - 18 years
• Fulfill criteria for membership in the PANDAS subgroup:
• Presence of OCD and/or tic disorder
• Prepubertal symptom onset
• Abrupt onset and episodic (relapsing-remitting) symptom course
• Association between symptom exacerbations and GABHS infections
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institute of Mental Health (NIMH)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Garvey MA, Perlmutter SJ, Allen AJ, Hamburger S, Lougee L, Leonard HL, Witowski ME, Dubbert B, Swedo SE. A pilot study of penicillin prophylaxis for neuropsychiatric exacerbations triggered by streptococcal infections. Biol Psychiatry. 1999 Jun 15;45(12):1564-71. doi: 10.1016/s0006-3223(99)00020-7.

  PMID: 10376116 BACKGROUND

• Garvey MA, Giedd J, Swedo SE. PANDAS: the search for environmental triggers of pediatric neuropsychiatric disorders. Lessons from rheumatic fever. J Child Neurol. 1998 Sep;13(9):413-23. doi: 10.1177/088307389801300901.

  PMID: 9733286 BACKGROUND

• Swedo SE, Leonard HL, Garvey M, Mittleman B, Allen AJ, Perlmutter S, Lougee L, Dow S, Zamkoff J, Dubbert BK. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry. 1998 Feb;155(2):264-71. doi: 10.1176/ajp.155.2.264.

  PMID: 9464208 BACKGROUND

MeSH Terms

Conditions

Obsessive-Compulsive Disorder; Streptococcal Infections; Tic Disorders

Interventions

Penicillins

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Neurodevelopmental Disorders

Intervention Hierarchy (Ancestors)

beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: April 1, 1993
• Study Completion: January 1, 2006
• Last Updated: March 4, 2008

Record last verified: 2006-01

Locations

US (1)