Clinical trial NCT00605995: Add-on Simvastatin in Schizophrenia Trial
Official title: Add-on Simvastatin in Schizophrenia Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Schizophrenia
Keywords: Schizophrenia
Randomized trial
Statin
Placebo
Lead sponsor: New York State Psychiatric Institute
Sponsor class: OTHER
Collaborators: name: Stanley Medical Research Institute
name: Sheba Medical Center
name: Merck Sharp & Dohme LLC
First posted: 2008-02-01
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The overall purpose of this study is to determine whether the cholesterol-lowering drug simvastatin is effective in the treatment of symptoms of schizophrenia. The primary hypothesis is that patients with schizophrenia receiving add-on treatment with simvastatin will improve clinically (as measured mainly by symptom severity) compared with patients receiving placebo, and that this improvement will be accompanied by concomitant reduction in peripheral inflammatory markers.

Detailed description: The identification of alternative therapies with the capacity to dampen inflammatory processes and reduce serum cholesterol takes on additional significance given independent concerns about heightened cardiovascular risk in schizophrenia patients, through exposure to antipsychotic drugs, increased cholesterol levels, metabolic syndrome and obesity, and smoking.

Eligibility criteria: Inclusion Criteria:

* Age 18-70 years
* Available for follow up during the study protocol
* DSM-IV schizophrenia
* Positive and Negative Syndrome Scale (PANSS) baseline score of ≥50
* Score of 3 or higher on the Severity of Illness scale of the Clinical Global Impression (CGI)
* Not completely refractory to antipsychotics: evidence for at least partial responsiveness to antipsychotic medication
* Evidence for current clinical stability
* Capacity to provide informed consent
* Provided informed consent
* Patients taking concomitant, non-investigational medications that are not listed in Exclusion Criteria #1
* Patients speaking Spanish or English
* Women using acceptable methods of birth control, including barrier method

Exclusion Criteria:

* Currently taking a statin OR any of the following:

  * Other lipid-lowering drug;
  * Anti-inflammatory drugs or aspirin;
  * Systemic antibiotic, anti-viral or anti-fungal drugs (within the past 4 weeks);
  * Potent inhibitors of the cytochrome P450 isoform 3A4 (CYP3A4);
  * Digoxin (Lanoxin®), nefazodone (Serzone®), niacin, cyclosporine (Neoral®, Sandimmune®), danazol, warfarin (Coumadin®), amiodarone, verapamil, Cordarone®, or Inderal®.
* Patients with known hypersensitivity to simvastatin or any other statin drug
* Active liver disease or unexplained persistent elevations of serum transaminases
* Renal insufficiency
* Serious or unstable medical condition that require close medical attention, such as cancer, unstable heart failure, uncontrolled hypertension/asthma/COPD
* Current drug use disorder (abuse/dependence)
* Pregnancy and lactation
* Psychiatric disorders other than schizophrenia or schizoaffective disorder requiring pharmacotherapy
* Suicidal or homicidal intent
* Severe cognitive impairment that might compromise competency to sign informed consent or the validity of the cognitive outcome measure
* Organic brain disorder, including epilepsy; mental retardation; or a medical condition whose pathology or treatment would likely alter the presentation or treatment of schizophrenia
* Current participation in another clinical trial
* Patients on more than 2 anti-psychotic medications (patients will not be tapered off effective medications for the purpose of participating in research)
* LDL cholesterol \>100 mg/dL with known coronary hard disease. LDL cholesterol \>130 mg/dl with 2 or more of the following risk factors: smoking; hypertension; low HDL cholesterol (\<40 mg/dL); age \>45 years (men) or age \>55 years (women); family history of premature CHD (CHD in 1st degree relative male\<55; female \<65

Primary outcomes:
measure: Positive and negative symptoms of schizophrenia
timeFrame: 12 weeks
Secondary outcomes:
measure: Serum inflammatory markers and cholesterol levels.
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
Study officials:
affiliation: Columbia University
name: Raz Gross, M.D., MPH
role: PRINCIPAL_INVESTIGATOR
References: