Trial of Naproxen Sodium for the Treatment of OCD in Children With PANDAS

Sponsor

Massachusetts General Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04015596

Collaborator

(none)

Enrollment

Location

Arms

24.3

Anticipated Duration (Months)

2.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This project aims to rigorously evaluate a potential treatment for inflammation-related Obsessive-Compulsive Disorder (OCD) symptoms in children. To accomplish this goal, the investigators will conduct a double-blind, randomized, placebo-controlled trial of Naproxen Sodium, a nonsteroidal anti-inflammatory drug (NSAID) in participants diagnosed with Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections (PANDAS). This research fills a gap in the empirical evidence base for the treatment of PANDAS, and will add to a growing literature of empirically-derived practices for PANDAS.

Condition or Disease	Intervention/Treatment	Phase
PANDAS Anxiety Disorder Autoimmune Diseases Obsessive-Compulsive Disorder	Drug: Naproxen Sodium Other: Placebo	Phase 4

Detailed Description

The investigators propose to systematically evaluate the effects of naproxen sodium on anti-obsessional and behavioral improvement and conduct the first randomized controlled trial of naproxen sodium in the treatment of children with PANDAS. The study will involve an 8-week, double-blinded randomized controlled trial to evaluate the efficacy of naproxen sodium (10mg/kg, by mouth, twice a day) versus placebo to treat OCD symptoms in children with PANDAS. The investigators will acquire completed data on 44 children with PANDAS for this pilot study (i.e., 22 randomized to active treatment; 22 randomized to placebo). Outcome will be assessed comparing pre- and post-treatment OCD symptom severity using a standardized, clinician-administered interview assessing OCD symptoms by an independent rater blind to treatment assignment.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

70 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Double-Blind, Randomized, Placebo-Controlled Trial of Naproxen Sodium for the Treatment of Obsessive Compulsive Symptoms in Pediatric Autoimmune Neuropsychiatric Disorder Associated With Streptococcal Infections (PANDAS)

Actual Study Start Date :

Oct 20, 2020

Anticipated Primary Completion Date :

Oct 31, 2022

Anticipated Study Completion Date :

Oct 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention Participants receive Naproxen Sodium.	Drug: Naproxen Sodium Dosed by weight (10mg/kg), twice daily, for 8 weeks
Placebo Comparator: Placebo Participants receive placebo.	Other: Placebo Participants take placebo pills twice daily, for 8 weeks.

Arm

Intervention/Treatment

Experimental: Intervention

Participants receive Naproxen Sodium.

Drug: Naproxen Sodium

Dosed by weight (10mg/kg), twice daily, for 8 weeks

Placebo Comparator: Placebo

Participants receive placebo.

Other: Placebo

Participants take placebo pills twice daily, for 8 weeks.

Outcome Measures

Primary Outcome Measures

Children's Yale-Brown Obsessive-Compulsive Scale, 2nd Edition (CY-BOCS-II) [Pre- to Post-8 week treatment]
The CY-BOCS-II is a clinician-rated measure to assess obsessive-compulsive symptom severity. This results in two subscale total scores, Obsessions and Compulsion, each ranging from 0-25, with a higher score indicating more symptom severity. These subscale scores are summed to provide a total score, ranging from 0 to 50, that is used to measure overall OCD symptom severity.
Children's Yale-Brown Obsessive-Compulsive Scale, 1st Edition (CY-BOCS-I) [Pre- to Post-8 week treatment]
The CY-BOCS-I is a clinician-rated measure to assess obsessive-compulsive symptom severity. This results in two subscale total scores, Obsessions and Compulsion, each ranging from 0-20, with a higher score indicating more symptom severity. These subscale scores are summed to provide a total score, ranging from 0 to 40, that is used to measure overall OCD symptom severity.

Secondary Outcome Measures

Changes in C reactive protein pre- and post-treatment between groups [Pre- to Post-8 week treatment]
C reactive protein (CRP, mg/L) will be obtained from pre- and post-blood draws and will be compared between groups.
Changes in erythrocyte sedimentation rate pre- and post-treatment between groups [Pre- to Post-8 week treatment]
Erythrocyte sedimentation rate (ESR, mm/h) will be obtained from pre- and post-blood draws and will be compared between groups.

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 15 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

significantly interfering Obsessive-Compulsive Disorder (OCD) symptoms
ages 6- to 15-years-old
new-onset of OCD symptoms within the previous 18 months
sufficient fluency of English to understand study staff, procedures and questionnaires,
able to take medication in pill form
parent/legal guardian who can provide informed consent.

Patients must also meet all criteria for PANDAS, which are:

prepubertal symptom onset
acute onset of symptoms (from no/minimal symptoms to maximum severity within 24-48 hours) and/or an episodic (relapsing-remitting) course
temporal association between symptomatic periods and infections with Group A Streptococcus (GAS) infection
presence of neurological abnormalities (e.g. handwriting deterioration, choreiform movements).

The onset/exacerbation of OCD symptoms must also be accompanied by at least three of the following clinical signs and symptoms, including:

Markedly increased level of anxiety, particularly new onset of separation anxiety
Emotional lability, irritability, aggressive behavior and/or personality change
Sudden difficulties with concentration or learning
Developmental regression ("baby-talk", temper tantrums).
Sleep disorder (insomnia, night terrors, refusal to sleep alone)
Handwriting deterioration or other sign of motoric dysfunction (including new onset of motor hyperactivity, presence of choreiform finger movements, pronator drift or truncal instability)
Urinary frequency or increased urge to urinate; daytime or night-time secondary enuresis

These co-occurring symptoms must be "severe" or "dramatic" and proceed from no/minimal symptoms to maximum severity within the same 24-48 hour interval during which the OCD symptoms arose. In addition to these inclusion criteria, PANDAS subjects will be required to provide documentation of a positive GAS infection via medical records. As the time between a documented GAS infection and the onset of PANDAS symptoms has not been defined in the PANDAS diagnostic criteria, the investigators will use a guideline of approximately six weeks or less between a documented GAS infection and the onset of OCD symptoms for inclusion into the study.

Exclusion Criteria:

child who is acutely psychotic or suicidal
child has a serious neurological disorder or impairment (e.g. brain damage, blindness, deafness), an intellectual disability, or autism
history of immune modulating therapies for OCD/PANDAS symptoms
pre-existing liver, kidney, GI bleeding or clotting disorders (GFR <75 mL/min/1.73m2)
history of ulcers in the digestive system
history of restricted fluid intake, as this could exacerbate side effects
concurrent antibiotic treatment or antibiotic treatment within one-week of baseline
pregnant or becomes pregnant
currently engaged in an intensive outpatient cognitive behavioral treatment program (more than weekly)
concurrent selective serotonin reuptake inhibitor (SSRI) or other psychoactive medication treatment except and unless the dose has been stable for at least 6 weeks (i.e. no recent titration, initiation, or change in dosage)
concurrent medications that do not meet the above criteria (e.g., other psychotropic medications or anti-inflammatory agents)
history of severe asthma or currently uncontrolled asthma