Clinical trial NCT04015596: Trial of Naproxen Sodium for the Treatment of OCD in Children With PANDAS
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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: PANDAS
Anxiety Disorder
Autoimmune Diseases
Obsessive-Compulsive Disorder
Keywords: PANDAS
Children
Obsessive-Compulsive Disorder
Anxiety
NSAID
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2019-07-11
Enrollment: 70
Sex: ALL
Minimum age (years): 6
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Children's Yale-Brown Obsessive-Compulsive Scale, 2nd Edition (CY-BOCS-II)
timeFrame: Pre- to Post-8 week treatment
measure: Children's Yale-Brown Obsessive-Compulsive Scale, 1st Edition (CY-BOCS-I)
timeFrame: Pre- to Post-8 week treatment
Secondary outcomes:
measure: Changes in C reactive protein pre- and post-treatment between groups
timeFrame: Pre- to Post-8 week treatment
measure: Changes in erythrocyte sedimentation rate pre- and post-treatment between groups
timeFrame: Pre- to Post-8 week treatment
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
References: