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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Autoimmune Diseases; Obsessive-Compulsive Disorder; PANDAS; Anxiety Disorder
• Intervention / Treatment: Drug: Naproxen Sodium; Other: Placebo

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 Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Sarah O'Dor, PhD; Phone Number: 617-643-6688; Email: sodor@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Sarah O'Dor, PhD; Phone Number: 617-726-8508; Email: PANDASclinic@partners.org
      • Contact: Saffron Homayoun
      • Principal Investigator: Kyle Williams, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

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

1. prepubertal symptom onset
2. acute onset of symptoms (from no/minimal symptoms to maximum severity within 24-48 hours) and/or an episodic (relapsing-remitting) course
3. temporal association between symptomatic periods and infections with Group A Streptococcus (GAS) infection
4. 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:

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).
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, presence of choreiform finger movements, pronator drift or truncal instability)
7. 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:

1. child who is acutely psychotic or suicidal
2. child has a serious neurological disorder or impairment (e.g. brain damage, blindness, deafness), an intellectual disability, or autism
3. history of immune modulating therapies for OCD/PANDAS symptoms
4. pre-existing liver, kidney, GI bleeding or clotting disorders (GFR <75 mL/min/1.73m2)
5. history of ulcers in the digestive system
6. history of restricted fluid intake, as this could exacerbate side effects
7. concurrent antibiotic treatment or antibiotic treatment within one-week of baseline
8. pregnant or becomes pregnant
9. currently engaged in an intensive outpatient cognitive behavioral treatment program (more than weekly)
10. 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)
11. concurrent medications that do not meet the above criteria (e.g., other psychotropic medications or anti-inflammatory agents)
12. history of severe asthma or currently uncontrolled asthma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Children's Yale-Brown Obsessive-Compulsive Scale, 2nd Edition (CY-BOCS-II)	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.	Pre- to Post-8 week treatment
Children's Yale-Brown Obsessive-Compulsive Scale, 1st Edition (CY-BOCS-I)	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.	Pre- to Post-8 week treatment

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2020
• Primary Completion (Anticipated): October 31, 2024
• Study Completion (Anticipated): October 31, 2024

Study Registration Dates

• First Submitted: June 11, 2019
• First Submitted That Met QC Criteria: July 9, 2019
• First Posted (Actual): July 11, 2019

Study Record Updates

• Last Update Posted (Actual): March 27, 2023
• Last Update Submitted That Met QC Criteria: March 23, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Anxiety; Children; NSAID; Obsessive-Compulsive Disorder; PANDAS
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Immune System Diseases; Personality Disorders; Disease; Compulsive Personality Disorder; Obsessive-Compulsive Disorder; Anxiety Disorders; Autoimmune Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Gout Suppressants; Naproxen
• Other Study ID Numbers: 2019P000623

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes