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Schizophrenia | Simvastatin Addition for Patients With Recent-onset Schizophrenia

Schizophrenia research study

What is the primary objective of this study?

Rationale: There is ample evidence that inflammatory processes play a role in the pathophysiology of schizophrenia. Although Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) have been shown to be able to reduce symptoms in these patients, these drugs either have unfavourable cardiovascular side effects or are otherwise not well tolerated. Moreover, patients with schizophrenia already tend to have an increased cardiovascular risk. The combination of well-established vascular protection and reduction of inflammation by simvastatin offers a highly attractive potential to further improve the treatment of schizophrenia and related disorders. Hypotheses: Daily treatment with 40mg simvastatin in addition to antipsychotic treatment reduces psychotic symptoms, improves cognition, attenuates brain volume loss, and decreases the risk for metabolic syndrome as well as for movement disorders, when compared to placebo. Objective: The primary objective of this trial is to investigate the proposed beneficial effect of simvastatin as compared to placebo when given for one year in addition to antipsychotic medication to patients with psychotic disorder. We expect lower symptom severity as measured with the PANSS (Positive and Negative Syndrome Scale) and less cognitive decline as measured with the BACS (Brief Assessment of Cognition in Schizophrenia).Secondary objectives are assessment of general functioning, presence and severity of metabolic syndrome and degree of movement disorders, and assessments of brain volume. Lastly, we examine various immunological parameters in serum and peripheral blood mononuclear cells and the experience of childhood trauma. Study design: Randomized placebo-controlled double-blind trial. Study population: 250 men and women, between 18 and 50 years of age, diagnosed with schizophrenia, schizoaffective or schizophreniform disorder (DSM-IV 295.*) or psychosis NOS (not otherwise specified) (298.9). Onset of first psychosis no longer than 3 years ago. Intervention: Patients will be randomized 1:1 to either 40 mg simvastatin or placebo daily, in the form of identical tablets.

Who is eligible to participate?

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 Exclusion Criteria: - Fulfilment of criteria for statin prescription; according to the Dutch Heart Foundation, 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 (Summary of Product Characteristics) - 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 aminotransferase (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 carbamazepin, efavirenz, nevirapine, etravirine (can be washed out before start of trial) - Use of comedication that may increase the risk for myalgia, rhabdomyolysis and myopathy, including colchicine, bosentan, phenobarbital, phenytoin, hypericum, rifabutin, rifampicin, fibrates (e.g. gemfibrozil), fusidic acid, carbamazepin (can be washed out before start of trial) For patients, the MRI scan requires addition exclusion criteria to be eligible to participate in this part of the study (if these additional criteria are not 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

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Schizophrenia

Schizoaffective Disorder

Schizophreniform Disorder

Psychosis NOS

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Drug:SimvastatinThe lipid-lowering drug simvastatin is added to normal antipsychotic treatment. One 40 mg simvastatin tablet daily for the treatment period of one year.

Drug:PlaceboPlacebo is added to normal antipsychotic treatment. One identical looking placebo tablet daily for the treatment period of one year.

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

SimvastatinThe lipid-lowering drug simvastatin is added to normal antipsychotic treatment. One 40 mg simvastatin tablet daily for the treatment period of one year.

PlaceboPlacebo is added to normal antipsychotic treatment. One identical looking placebo tablet daily for the treatment period of one year.

Study Status

Recruiting

Start Date: October 2013

Completed Date: October 2017

Phase: Phase 3

Type: Interventional

Design:

Primary Outcome: Total symptom severity

Secondary Outcome: Change in positive, negative and general symptom severity

Study sponsors, principal investigator, and references

Principal Investigator: Iris EC Sommer, Prof. dr.

Lead Sponsor: Iris Sommer

Collaborator: Stanley Medical Research Institute

More information:https://clinicaltrials.gov/show/NCT01999309

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