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    The EU Clinical Trials Register currently displays   43628   clinical trials with a EudraCT protocol, of which   7211   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    EudraCT Number:2013-000834-36
    Sponsor's Protocol Code Number:43806
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2013-06-05
    Trial results View results
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    A. Protocol Information
    A.1Member State ConcernedNetherlands - Competent Authority
    A.2EudraCT number2013-000834-36
    A.3Full title of the trial
    Simvastatin addition to improve symptoms, cognition and metabolic syndrome in patients with recent-onset schizophrenia.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    The effect of simvastatin addition to improve symptoms, mental abilities and metabolic syndrome in patients with recent-onset schizophrenia.
    A.3.2Name or abbreviated title of the trial where available
    Simvastatin in patients with recent-onset schizophrenia.
    A.4.1Sponsor's protocol code number43806
    A.5.4Other Identifiers
    Name:ClinicalTrials.govNumber:To be completed soon
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorUniversity Medical Center Utrecht
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportThe Stanley Foundation
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUniversity Medical Center Utrecht
    B.5.2Functional name of contact pointM.J.H. Begemann
    B.5.3 Address:
    B.5.3.1Street AddressHeidelberglaan 100
    B.5.3.2Town/ cityUtrecht
    B.5.4Telephone number+88887550880
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D. name Simvastatin
    D. of the Marketing Authorisation holderGenthon B.V.
    D.2.1.2Country which granted the Marketing AuthorisationNetherlands
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameSimvastatin
    D.3.2Product code SUB10529MIG
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product No
    D. ATIMP (i.e. one involving a medical device) No
    D. on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Schizophrenia, schizoaffective or schizophreniform disorder (DSM-IV 295.*) or psychosis NOS (not otherwise specified) (298.9)
    E.1.1.1Medical condition in easily understood language
    Schizophrenia or related disorders
    E.1.1.2Therapeutic area Psychiatry and Psychology [F] - Mental Disorders [F03]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    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).
    E.2.2Secondary objectives of the trial
    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).
    E.2.3Trial contains a sub-study No
    E.3Principal 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.
    E.4Principal 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)
    E.5 End points
    E.5.1Primary 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.
    E.5.1.1Timepoint(s) of evaluation of this end point
    After 12 months of treatment.
    E.5.2Secondary 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-γ, interleukin (IL)-1RA, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, L-17, tumor necrosis factor-alpha (TNF-α), 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).
    E.5.2.1Timepoint(s) of evaluation of this end point
    After 12 months of treatment.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E. trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) Yes
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    Last patient last visit.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 250
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state250
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Treatment with simvastatin can be continued thourgh normal daily practice.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2013-06-05
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-09-26
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2019-12-19
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