Obsessive Compulsive Disorder Clinical Trial
Official title:
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.
Status | Completed |
Enrollment | 90 |
Est. completion date | January 2006 |
Est. primary completion date | |
Accepts healthy volunteers | No |
Gender | Both |
Age group | N/A and older |
Eligibility |
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 |
Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
United States | National Institute of Mental Health (NIMH) | Bethesda | Maryland |
Lead Sponsor | Collaborator |
---|---|
National Institute of Mental Health (NIMH) |
United States,
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. Review. — View Citation
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. — View Citation
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. Erratum in: Am J Psychiatry 1998 Apr;155(4):578. — View Citation
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT04631042 -
Developing Brain, Impulsivity and Compulsivity
|
||
Completed |
NCT02855580 -
Integrating Pharmacogenomic Testing Into a Child Psychiatry Clinic
|
||
Completed |
NCT02202915 -
CBT for Pediatric OCD: Community Training Pilot
|
N/A | |
Completed |
NCT02229903 -
An Evaluation of the Safety and Efficacy of the dTMS Treatment for OCD
|
N/A | |
Completed |
NCT01794156 -
Evaluation of a Cognitive Therapy (Inference-based-therapy) for the Treatment of Obsessional Compulsive Disorder
|
N/A | |
Completed |
NCT02089984 -
Web Based Therapist Training on Cognitive Behavior Therapy for Anxiety Disorders
|
N/A | |
Completed |
NCT01348529 -
Internet Cognitive Behavior Therapy (CBT) for Obsessive Compulsive Disorder (OCD)
|
N/A | |
Recruiting |
NCT00965211 -
Evaluation of the HBDL Coil Transcranial Magnetic Stimulation (TMS) Device - Safety and Feasibility Study for the Treatment of Tourette Syndrome
|
N/A | |
Completed |
NCT01172873 -
D-Cycloserine Augmentation to CBT With Exposure and Response Prevention in Adults and Adolescents With OCD
|
N/A | |
Completed |
NCT00723060 -
Comparison of Effects Between Conventional Dose and High Dose Escitalopram on Clinical Improvement in Patients With Obsessive-compulsive Disorder
|
Phase 4 | |
Not yet recruiting |
NCT00743834 -
Cost-Effectiveness of Adding Web-Based Cognitive-Behavioral Therapy (CBT) to Luvox CR for Obsessive Compulsive Disorder (OCD)
|
Phase 4 | |
Completed |
NCT02421315 -
Overlapping Neural Circuits in Pediatric OCD
|
N/A | |
Completed |
NCT01981317 -
Stepped Care Cognitive Behavioral Therapy for Pediatric Obsessive Compulsive Disorder
|
N/A | |
Completed |
NCT02194075 -
Methylphenidate Hydrochloride Controlled-Release Tablets Augmentation Strategy for Patients With Obsessive Compulsive Disorder
|
Phase 4 | |
Completed |
NCT01686087 -
Attaining and Maintaining Wellness in Obsessive-compulsive Disorder
|
N/A | |
Terminated |
NCT00997087 -
A Randomized, Double-Blind, Placebo-Controlled Trial of Flumazenil for the Treatment of Obsessive Compulsive Disorder
|
Phase 2 | |
Completed |
NCT01331876 -
Modification of Cerebral Activity of Obsessive Compulsive Disorder (OCD) Patients During Cognitive and Behavioral Therapy
|
N/A | |
Completed |
NCT00533806 -
Comparing the Effectiveness of Two Family-based Therapies in Treating Young Children With Obsessive-Compulsive Disorder
|
Phase 3 | |
Completed |
NCT00517244 -
Evaluating Parenting Styles and Child Temperament Associated With Child Anxiety Disorders
|
N/A | |
Completed |
NCT00169377 -
Subthalamic Nucleus (STN) Stimulation and Obsessive-Compulsive Disorder (OCD)
|
Phase 1/Phase 2 |