Schizophrenia
Conditions
Interventions
Patients will be randomized 1:1 to either 40 mg simvastatin or placebo daily,
in the form of identical tablets.
Sponsors
Universitair Medisch Centrum Utrecht
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: A DSM-IV-R diagnosis of: 295.x (schizophrenia, schizophreniform disorder, or schizoaffective disorder) or 298.9 (psychosis NOS); Onset of first psychosis no longer than 3 years ago; Age between 18 and 50 years; Written informed consent is obtained; Female patients of childbearing potential need to utilize a proper method of contraception (the pill, vaginal ring, hormonal patch, intrauterine device, cervical cape, condom, contraceptive injection, diaphragm) in case of sexual intercourse during the study.
Exclusion criteria
Exclusion criteria: Fulfilment of criteria for statin prescription; according to the Dutch Heart Foundation (Hartstichting), statin treatment is indicated when the total cholesterol level is > 8 mmol/l (www.hartstichting.nl); 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 (temporary use is permitted, if stopped at least 1 month before start of treatment trial); Pregnancy or breast-feeding (urine pregnancy test will be performed for sexually active females with child bearing potential); In case of familial risk for muscular disorders or previously experienced muscle toxicity when taking medication similar to simvastatin, creatine kinase (CK) levels will also be checked (as recommended by the Dutch Farmacotherapeutisch Kompas, www.farmacotherapeutischkompas.nl/); In addition, levels of aspartate (ASAT), alanine aminotransferase (ALAT), gamma-glutamyltranspeptidase (gamma-GT) and creatinine will be checked when a history of alcohol abuse, liver or kidney disorders is reported based as recommended by the Dutch Farmacotherapeutisch Kompas, www.farmacotherapeutischkompas.nl/); 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). The MRI scan requires additional exclusion criteria to be eligible to participate in this part of the study (if these additional criteria are met, patients can participate in the study but not in the MRI component): Ferrous objects in or around the body (e.g. braces, glasses, pacemaker, metal fragments) Claustrophobia
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. In addition, we will examine neurocognitive functioning as measured with the Brief Assessment of Cognition in Schizophrenia (BACS; Keefe et al. 2004). | — |
Secondary
| Measure | Time frame |
|---|---|
| Our secondary study parameters are the PANSS subscales: the positive scale, negative scale and general psychopathology scale. Furthermore, general assessment of functioning will be evaluated using the Global Assessment of Functioning scale (GAF; Jones et al. 1995), 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), and presence and severity of movement disorders using validated scales. MRI will be used to investigate changes in the structural properties of the brain. These parameters will be compared after 12 months of treatment, between patients treated with simvastatin versus placebo. Other parameters are severity of depression as assessed with the Calgary Depression Scale for Schizophrenia (CDSS; Addington et al. 1993) and experience of childhood trauma will be evaluated with the Childhood Trauma Questionnaire Short Form (CTQ-SF). In addition, in order to investigate immunological and metabolic biomarkers that predict treatment response to simvastatin therapy, serum, peripheral blood mononuclear cells (PBMC) and RNA of all patients will be analyzed. | — |
Countries
Netherlands
Outcome results
None listed