Schizoaffective Disorder, Schizophrenia
Conditions
Keywords
Schizophrenia, Cognition, Metabolism, Antipsychotics, Psychopathology
Brief summary
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
The specific aims include: Primary aims: 1. 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). 2. 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.
Interventions
DRUGsalsalate
open-label trial of salsalate 3g/day for 12 weeks.
Sponsors
National Institutes of Health (NIH)
University of Massachusetts, Worcester
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PANSS- Negative Score | Baseline, 12 weeks | 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. |
| SANS Total Score | Baseline, 12 weeks | 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. |
| MATRICS Composite Score | Baseline, 12 weeks | 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. |
| PANSS Positive Score | Baseline, 12 weeks | 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. |
| PANSS Total Score | Baseline and 12 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| TNF-alpha | Baseline,12 weeks | Tumor necrosis-alpha factor will be measured to assess inflammation levels. |
| IL-6 | Baseline, week 12 | IL-6 (interleukin 6) is a marker used to measure inflammation. |
| Hs-CRP | Baseline, 12 weeks | 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. |
Countries
United States
Participant flow
Pre-assignment details
A total of 17 subjects consented and were screened, 4 of which were screen fails. The remaining 13 received the study medication.
Participants by arm
| Arm | Count |
|---|---|
| Salsalate salsalate: open-label trial of salsalate 3g/day for 12 weeks. | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 3 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Salsalate |
|---|---|
| Age, Continuous | 42.8 years STANDARD_DEVIATION 9.8 |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 7 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
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.
Time frame: Baseline, 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salsalate | MATRICS Composite Score | Baseline | 27.9 t-score | Standard Deviation 11.9 |
| Salsalate | MATRICS Composite Score | Week 12 | 31.6 t-score | Standard Deviation 15.2 |
Primary
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.
Time frame: Baseline, 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salsalate | PANSS- Negative Score | Baseline | 18.5 units on a scale | Standard Deviation 6.5 |
| Salsalate | PANSS- Negative Score | Week 12 | 17.4 units on a scale | Standard Deviation 6.1 |
Primary
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.
Time frame: Baseline, 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salsalate | PANSS Positive Score | Baseline | 13.0 units on a scale | Standard Deviation 5.4 |
| Salsalate | PANSS Positive Score | Week 12 | 10.9 units on a scale | Standard Deviation 4.4 |
Primary
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.
Time frame: Baseline and 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salsalate | PANSS Total Score | Baseline | 58.2 units on a scale | Standard Deviation 11.4 |
| Salsalate | PANSS Total Score | Week 12 | 53.5 units on a scale | Standard Deviation 11.9 |
Primary
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.
Time frame: Baseline, 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salsalate | SANS Total Score | Baseline | 33.0 units on a scale | Standard Deviation 15.7 |
| Salsalate | SANS Total Score | Week 12 | 33.0 units on a scale | Standard Deviation 12.9 |
Secondary
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.
Time frame: Baseline, 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salsalate | Hs-CRP | Week 12 | 2.0 mg/L | Standard Error 1.2 |
| Salsalate | Hs-CRP | Baseline | 3.0 mg/L | Standard Error 1.2 |
Secondary
IL-6
IL-6 (interleukin 6) is a marker used to measure inflammation.
Time frame: Baseline, week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salsalate | IL-6 | Baseline | 2.2 pg/mL | Standard Deviation 0.87 |
| Salsalate | IL-6 | Week 12 | 2.3 pg/mL | Standard Deviation 1 |
Secondary
TNF-alpha
Tumor necrosis-alpha factor will be measured to assess inflammation levels.
Time frame: Baseline,12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salsalate | TNF-alpha | Baseline | 8.2 pg/ml | Standard Deviation 3.7 |
| Salsalate | TNF-alpha | Week 12 | 8.7 pg/ml | Standard Deviation 3.6 |