Schizophrenia, schizoaffective or schizophreniform disorder (DSM-IV 295.*) or psychosis NOS (not otherwise specified) (298.9)
Conditions
Interventions
Trade Name: Simvastatin
Product Name: Simvastatin
Product Code: SUB10529MIG
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
Sponsors
University Medical Center Utrecht
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A DSM-IV-R diagnosis of: 295.x (schizophrenia, schizophreniform disorder, or schizoaffective disorder) or 298.9 (psychosis NOS), no longer than 3 years ago. Age between 18 and 50 years. Written informed consent is obtained. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 250 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Presence of any of the contra-indications or warnings for the use of simvastatin as reported in the SPC Chronic use of glucocorticosteroids (temporary use is permitted, if stopped at least 1 month before start of treatment trial) Chronic use of non-steroidal anti-inflammatory drugs (temporary use is permitted, if stopped at least 1 month before start of treatment trial) Current use of statins or other lipid-lowering drugs Pregnancy or breast-feeding Active liver, kidney or muscle disease as defined by alanine amino transferase (ALAT), creatinine or creatine kinase (CK) levels more than two times the upper boundary of normal levels Use of comedication that either inhibits or induces the live enzyme CYP3A4 which is responsible for the degradation of simvastatin. Inhibitors of CYP3A4 include itraconazole, ketoconazole, posaconazole, fluconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone, telaprevir, boceprevir, imatinib, ticagrelor, voriconazole; inducers of CYP3A4 include carbamazepine, efavirenz, nevirapin, etravirin (can be washed out before start of trial) Use of comedication that may increase the risk for myalgia, rhabdomyolyse and myopathy, including colchicine, bosentan, fenobarbital, fenytoin, hypericum, rifabutin, rifampicin, fibrates (e.g. gemfibrozil), fusidic acid, carbamazepine (can be washed out before start of trial)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this trial is to investigate the proposed beneficial effect of simvastatin as compared to placebo when given in addition to antipsychotic medication on symptom severity as measured through Positive and Negative Syndrome Scale (PANSS). ;Secondary Objective: Secondary objectives are assessment of general functioning using the General Assessment of Functioning (GAF), neurocognitive functioning with the B-CATS (Brief Cognitive Assessment Tool for Schizophrenia) and a shift in immunological parameters into the direction of anti-inflammation measured in serum and lower severity of metabolic syndrome, as defined by the American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLB). ;Primary end point(s): Our main study parameter is symptom severity as measured with the Positive and Negative Syndrome Scale (PANSS) (Kay et al. 1987). We will compare the effect of simvastatin versus placebo, both given in addition to antipsychotic medication, with regards to change in symptom severity expressed as overall PANSS score after 12 months of treatment. ;Timepoint(s) of evaluation of this end point: After 12 months of treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Our secondary study parameters are the PANSS subscales: the positive scale, negative scale and general psychopathology. Furtermore, general assessment of functioning will be evaluated using the Global Assessment of Functioning scale (GAF; Jones et al. 1995), in addition to cognitive functioning as assessed with the B-CATS (Brief Cognitive Assessment Tool for Schizophrenia; Hurford et al. 2011), and presence and severity of metabolic syndrome as defined by the American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLB; Grundy et al. 2005). These parameters will be compared after 12 months of treatment, between patients treated with simvastatin versus placebo. Furthermore, immunological processes may be involved in a subpopulation of patients with schizophrenia and are targeted with simvastatin in this study. We will therefore collect serum and peripheral blood mononuclear cells of all patients at baseline, as well as 1, 6, and 12 months post-baseline to analyze whether we can find biomarkers to predict treatment response using augmentation with simvastatin. Since infectious agents have been implicated in schizophrenia (Yolken and Torrey 2008) we will also determine seroconversion to pathogens that have been associated with schizophrenia, including herpes simplex virus, cytomegalovirus and toxoplasma Gondii at baseline, as such seroconversions provide another classification to define a subsample of patients with good treatment response. We will measure the levels of CRP, interferon-?, interleukin (IL)-1RA, IL-1ß, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, L-17, tumor necrosis factor-alpha (TNF-a), macrophage migration inhibitory factor, S-100B in peripheral blood at baseline, after 1, 6 months and after 12 months. Finally, severity of depression will be assessed using the Calgary Depression Scale for Schizophrenia (CDSS; Addington et al. 1993). ;Timepoint(s) of evaluation of this end point: After 12 months of treatment. | — |
Countries
Netherlands
Contacts
Public ContactM.J.H. Begemann
University Medical Center Utrecht
Outcome results
None listed