Schizoaffective Disorders, Schizophrenia, Schizophreniform Disorders
Conditions
Keywords
schizophrenia, pravastatin, inflammation, cognition, antipsychotics, cholesterol
Brief summary
This study involves people with schizophrenia or schizoaffective disorder, who are currently taking antipsychotic medications. Some antipsychotic medications may cause an increase in cholesterol levels, which may lead to inflammation in the body. Inflammation poses a risk in developing heart disease, diabetes and problems with brain function. The purpose of this study is to see if pravastatin can: * Lower cholesterol * Decrease inflammation * Improve cognition in patients with schizophrenia
Detailed description
This study is a 12-week randomized, double-blind, placebo-controlled pilot study of pravastatin 40mg a day, administered for 12 consecutive weeks to subjects with schizophrenia to examine pravastatin's effects on lowering cholesterol levels and inflammatory markers, and improving cognition. The study will be conducted at the Freedom Trail Clinic and will use the Massachusetts General Hospital Clinical Research Center. The innovative approach of using pravastatin to not only decrease cholesterol levels, but to decrease inflammation and improve cognition in patients with schizophrenia is promising and may lead to a different approach to treatment in this population.
Interventions
DRUGPravastatin
pravastatin 40mg, or placebo, once a day, shortly after baseline for 12 consecutive weeks
DRUGPlacebo
pravastatin 40mg, or placebo, once a day, shortly after baseline for 12 consecutive weeks
Sponsors
Stanley Medical Research Institute
North Suffolk Mental Health Association
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 68 Years
Healthy volunteers
No
Inclusion criteria
* Male or female * Age 18-68 years * Diagnosis of schizophrenia, any subtype, schizoaffective disorder, any subtype or schizophreniform disorder * Well established compliance with outpatient medications including their antipsychotic medication
Exclusion criteria
* Inability to provide informed consent * Current substance and alcohol abuse * Significant medical illness, including congestive heart failure, severe cardiovascular disease, renal disease (serum creatinine \> 1.5), severe hepatic impairment or active liver disease, anemia (hemoglobin \<11.0 gm/dL), history of severe head injury, and not treated muscle disease. * Psychiatrically unstable * Women of child bearing potential who are pregnant, breastfeeding, or who are unwilling or unable to use an effective form of birth control during the entire study * Subjects treated with anti-inflammatory drugs (including daily aspirin and ibuprofen), thiazide diuretics; agents that induce weight loss, and St. John's Wort will be excluded from the study * Current history of untreated thyroid disease * Current treatment with insulin * Subjects being treated with drugs such as: colchicine, azole antifungals (fluconazole, ketoconazole, itraconazole); macrolide antibiotics (clarithromycin, erythromycin); HIV protease inhibitors (ritonavir, indinavir, saquinavir, nelfinavir) that inhibit the CYP 450 3A liver enzyme * Known hypersensitivity to pravastatin or any of its components
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in LDL-cholesterol Between Baseline and Week 12 | Baseline, week 12 | — |
| Change in C-Reactive Protein (CRP) From Baseline to Week 12 | Baseline, week 12 | — |
| Change in MATRICS Neuropsychological Battery Composite Score From Baseline to Week 12 | Baseline, week 12 | The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery measures cognitive functioning within 7 domains: speed of processing, attention/vigilance, working memory (non verbal and verbal), verbal learning, visual learning, reasoning and problem solving and social cognition. The composite score is calculated by the MATRICS computer program, which equally weights each of the 7 domain scores. The range of composite scores is 20-80. Higher scores indicate higher levels or cognitive functioning, while lower scores indicate lower levels of cognitive functioning. |
| Change in Positive and Negative Syndrome Scale (PANSS) Total Score From Baseline to Week 12 | Baseline, week 12 | The Positive and Negative Syndrome Scale (PANSS) is a scale used to rate severity of schizophrenia. All items are summed to calculate the total score. The scale range is 30-210. Better outcomes have lower numbers and worse outcomes have higher numbers. |
| Change in Positive and Negative Syndrome Scale (PANSS) Positive Score From Baseline to Week 12 | Baseline, week 12 | This is a subscale of the Positive and Negative Syndrome Scale (PANSS). The range for this subscale is 7-49. All items are summed to calculate the total score. Better outcomes have lower numbers and worse outcomes have higher numbers. |
| Change in Positive and Negative Syndrome Scale (PANSS) Negative Score From Baseline to Week 12 | Baseline, week 12 | This is a subscale of the Positive and Negative Syndrome Scale (PANSS). The range for this subscale is 7-49. All items are summed to calculate the total score. Better outcomes have lower numbers and worse outcomes have higher numbers. |
| Change in Positive and Negative Syndrome Scale (PANSS) General Score From Baseline to Week 12 | Baseline, week 12 | This is a subscale of the Positive and Negative Syndrome Scale (PANSS). The range for this subscale is 15-105. All items are summed to calculate the total score. Better outcomes have lower numbers and worse outcomes have higher numbers. |
Countries
United States
Participant flow
Recruitment details
All participants were recruited from the Massachusetts General Hospital Schizophrenia Clinical and Research Program.
Participants by arm
| Arm | Count |
|---|---|
| Pravastatin pravastatin 40mg, or placebo, once a day, shortly after baseline for 12 consecutive weeks | 30 |
| Placebo pravastatin 40mg, or placebo, once a day, shortly after baseline for 12 consecutive weeks | 30 |
| Total | 60 |
Baseline characteristics
| Characteristic | Placebo | Pravastatin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants | 30 Participants | 60 Participants |
| Age, Continuous | 45.08 years STANDARD_DEVIATION 12.54 | 43.11 years STANDARD_DEVIATION 11.06 | 44.84 years STANDARD_DEVIATION 11.35 |
| Region of Enrollment United States | 30 participants | 30 participants | 60 participants |
| Sex: Female, Male Female | 14 Participants | 8 Participants | 22 Participants |
| Sex: Female, Male Male | 16 Participants | 22 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 30 | 1 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
Change in C-Reactive Protein (CRP) From Baseline to Week 12
Time frame: Baseline, week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pravastatin | Change in C-Reactive Protein (CRP) From Baseline to Week 12 | 0.8063 mg/L | Standard Deviation 5.3515 |
| Placebo | Change in C-Reactive Protein (CRP) From Baseline to Week 12 | -0.5136 mg/L | Standard Deviation 7.2646 |
Primary
Change in LDL-cholesterol Between Baseline and Week 12
Time frame: Baseline, week 12
Population: One participant from the pravastatin group and two from the placebo group had triglyceride levels above 400. Per Massachusetts General Hospital Laboratories policy, LDL is not run as a part of the complete metabolic panel (CMP) when triglycerides are above 400, and therefore could not be included in the final analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pravastatin | Change in LDL-cholesterol Between Baseline and Week 12 | -25.565 mg/dl | Standard Deviation 32.261 |
| Placebo | Change in LDL-cholesterol Between Baseline and Week 12 | -2.913 mg/dl | Standard Deviation 16.434 |
Primary
Change in MATRICS Neuropsychological Battery Composite Score From Baseline to Week 12
The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery measures cognitive functioning within 7 domains: speed of processing, attention/vigilance, working memory (non verbal and verbal), verbal learning, visual learning, reasoning and problem solving and social cognition. The composite score is calculated by the MATRICS computer program, which equally weights each of the 7 domain scores. The range of composite scores is 20-80. Higher scores indicate higher levels or cognitive functioning, while lower scores indicate lower levels of cognitive functioning.
Time frame: Baseline, week 12
Population: One participant from the placebo group refused to complete the MATRICS assessment at week 12; therefore, we could only analyze 24 placebo participants for the final analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pravastatin | Change in MATRICS Neuropsychological Battery Composite Score From Baseline to Week 12 | 4.0417 Scores on a scale | Standard Deviation 5.2789 |
| Placebo | Change in MATRICS Neuropsychological Battery Composite Score From Baseline to Week 12 | 4.125 Scores on a scale | Standard Deviation 6.9739 |
Primary
Change in Positive and Negative Syndrome Scale (PANSS) General Score From Baseline to Week 12
This is a subscale of the Positive and Negative Syndrome Scale (PANSS). The range for this subscale is 15-105. All items are summed to calculate the total score. Better outcomes have lower numbers and worse outcomes have higher numbers.
Time frame: Baseline, week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pravastatin | Change in Positive and Negative Syndrome Scale (PANSS) General Score From Baseline to Week 12 | -5.625 Scores on a scale | Standard Deviation 8.155 |
| Placebo | Change in Positive and Negative Syndrome Scale (PANSS) General Score From Baseline to Week 12 | -3.76 Scores on a scale | Standard Deviation 6.418 |
Primary
Change in Positive and Negative Syndrome Scale (PANSS) Negative Score From Baseline to Week 12
This is a subscale of the Positive and Negative Syndrome Scale (PANSS). The range for this subscale is 7-49. All items are summed to calculate the total score. Better outcomes have lower numbers and worse outcomes have higher numbers.
Time frame: Baseline, week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pravastatin | Change in Positive and Negative Syndrome Scale (PANSS) Negative Score From Baseline to Week 12 | -0.83 Scores on a scale | Standard Deviation 5.411 |
| Placebo | Change in Positive and Negative Syndrome Scale (PANSS) Negative Score From Baseline to Week 12 | -0.28 Scores on a scale | Standard Deviation 3.736 |
Primary
Change in Positive and Negative Syndrome Scale (PANSS) Positive Score From Baseline to Week 12
This is a subscale of the Positive and Negative Syndrome Scale (PANSS). The range for this subscale is 7-49. All items are summed to calculate the total score. Better outcomes have lower numbers and worse outcomes have higher numbers.
Time frame: Baseline, week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pravastatin | Change in Positive and Negative Syndrome Scale (PANSS) Positive Score From Baseline to Week 12 | -2.9583 Scores on a scale | Standard Deviation 3.014 |
| Placebo | Change in Positive and Negative Syndrome Scale (PANSS) Positive Score From Baseline to Week 12 | -2.44 Scores on a scale | Standard Deviation 4.164 |
Primary
Change in Positive and Negative Syndrome Scale (PANSS) Total Score From Baseline to Week 12
The Positive and Negative Syndrome Scale (PANSS) is a scale used to rate severity of schizophrenia. All items are summed to calculate the total score. The scale range is 30-210. Better outcomes have lower numbers and worse outcomes have higher numbers.
Time frame: Baseline, week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pravastatin | Change in Positive and Negative Syndrome Scale (PANSS) Total Score From Baseline to Week 12 | -9.416 Scores on a scale | Standard Deviation 13.941 |
| Placebo | Change in Positive and Negative Syndrome Scale (PANSS) Total Score From Baseline to Week 12 | -6.48 Scores on a scale | Standard Deviation 12.003 |