Salsalate as an Adjunctive Treatment for Patients With Schizophrenia

Study Overview
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Brief Summary
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This is a 12-week, open-label trial of salsalate 3 g/day as an adjunctive treatment in 15 schizophrenia subjects to examine salsalate's effect on psychopathology, cognitive functioning, and metabolic parameters. Potential subjects will be identified by their clinicians at the Freedom Trail Clinic, or Massachusetts General Hospital. A total of 15 subjects will be enrolled.

Detailed Description
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The specific aims include: Primary aims: Examine the efficacy of salsalate (3g/day) in improving positive and negative symptoms as measured by the Positive and Negative Syndrome Scale (PANSS) and the Scale for Assessment of Negative Symptoms (SANS). Examine the efficacy of salsalate in improving cognition as measured by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) composite score. Secondary aims: 1. Examine salsalate's effects on inflammatory markers such as high sensitivity C-reactive protein (hs-CRP), TNF-α and IL-6.

Official Title
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Salsalate as an Adjunctive Treatment for Patients With Schizophrenia

Conditions
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Schizophrenia, Schizoaffective Disorder

Intervention / Treatment
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* Drug: salsalate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-65 years; Diagnosis of schizophrenia or schizoaffective disorder; Stable dose of the current antipsychotic drug for at least one month; Well established compliance with outpatient treatment per treating clinician's judgment; Able to complete the cognitive assessment battery (must be English speaking); Female subjects will be eligible to participate in the study if they are of non-childbearing potential or of child-bearing potential and willing to practice appropriate birth control methods during the study. Exclusion Criteria: Inability to provide informed consent; Current substance abuse; Psychiatrically unstable per treating clinician's judgment; Significant medical illnesses including uncontrolled hypertension, diabetes, seizure disorder, severe cardiovascular, cerebrovascular, pulmonary, or thyroid diseases; Currently on immunosuppressant medication including oral steroids; Use of anti-coagulants (heparin, LMWH, warfarin, cilostazol, clopidogrel, dabigatran); History of chronic infection (including, HIV and hepatitis), malignancy, organ transplantation, blood dyscrasia, central nervous system demyelinating disorder, and any other known autoimmune or inflammatory condition; Experienced asthma, urticaria or allergic type reaction after taking aspirin, salsalate, or other NSAIDS; Pregnancy or breastfeeding; Pre-existing chronic tinnitus. Known hypersensitivity to salsalate.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: salsalate<br>open-label trial of salsalate 3g/day | Drug: salsalate<br>* open-label trial of salsalate 3g/day for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PANSS Total Score | Positive and negative symptoms of schizophrenia will be measured by total score on all subscales of the Positive and Negative Syndrome Scale (PANSS; score range 30-210). Higher scores correspond with worse outcomes. | Baseline and 12 weeks | 
| SANS Total Score | Negative symptoms of schizophrenia will be measured by total score on the Scale for Assessment of Negative Symptoms (SANS; score range 0-100). Higher scores correspond with worse outcomes. | Baseline, 12 weeks | 
| MATRICS Composite Score | Improved cognition will be measured using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) assessment. The MATRICS assessment includes a battery of tests, and the composite t-score measures cognition across 7 domains including speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. A higher score indicates better cognition. | Baseline, 12 weeks | 
| PANSS Positive Score | Subscale of Positive and Negative Syndrome Scale that specifically measures positive symptoms. The scores range from 7-49, with higher scores representing a worse outcome. | Baseline, 12 weeks | 
| PANSS- Negative Score | Subscale of Positive and Negative Syndrome Scale that specifically measures negative symptoms. The scores range from 7-49, with higher scores representing a worse outcome. | Baseline, 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hs-CRP | High-sensitivity C-reactive protein (hs-CRP) will be measured in mg/L in order to detect inflammation. Higher hs-CRP values correspond to higher levels of inflammation. | Baseline, 12 weeks | 
| TNF-alpha | Tumor necrosis-alpha factor will be measured to assess inflammation levels. | Baseline,12 weeks | 
| IL-6 | IL-6 (interleukin 6) is a marker used to measure inflammation. | Baseline, week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Cognition, Metabolism, Antipsychotics, Psychopathology