Add-on Simvastatin in Schizophrenia Trial (ASSIST)
Primary Purpose
Schizophrenia
Status
Terminated
Phase
Not Applicable
Locations
Israel
Study Type
Interventional
Intervention
Simvastatin
Sponsored by
About this trial
This is an interventional treatment trial for Schizophrenia focused on measuring Schizophrenia, Randomized trial, Statin, Placebo
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
Sites / Locations
- Sheba Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Simvastatin
Placebo
Arm Description
Simvastatin, 20 mg Tablet, given once daily. Dosage increased to 40 mg/day at the end of week 4 until endpoint.
Placebo pill, similar in its appearance to Simvastatin, taken once daily for the duration of the trial.
Outcomes
Primary Outcome Measures
Positive and negative symptoms of schizophrenia
Secondary Outcome Measures
Serum inflammatory markers and cholesterol levels.
Full Information
NCT ID
NCT00605995
First Posted
January 21, 2008
Last Updated
January 12, 2017
Sponsor
New York State Psychiatric Institute
Collaborators
Stanley Medical Research Institute, Sheba Medical Center, Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT00605995
Brief Title
Add-on Simvastatin in Schizophrenia Trial
Acronym
ASSIST
Official Title
Add-on Simvastatin in Schizophrenia Trial
Study Type
Interventional
2. Study Status
Record Verification Date
April 2012
Overall Recruitment Status
Terminated
Why Stopped
Enrollment was slower than anticipated by the investigators and the funding research foundation.
Study Start Date
February 2008 (undefined)
Primary Completion Date
August 2011 (Actual)
Study Completion Date
August 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
New York State Psychiatric Institute
Collaborators
Stanley Medical Research Institute, Sheba Medical Center, Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia
Keywords
Schizophrenia, Randomized trial, Statin, Placebo
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Simvastatin
Arm Type
Experimental
Arm Description
Simvastatin, 20 mg Tablet, given once daily. Dosage increased to 40 mg/day at the end of week 4 until endpoint.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo pill, similar in its appearance to Simvastatin, taken once daily for the duration of the trial.
Intervention Type
Drug
Intervention Name(s)
Simvastatin
Other Intervention Name(s)
Zocor
Intervention Description
20 mg taken orally once daily for the first 4 weeks. Dosage will be increased to 40 mg/day at the end of week 4.
Primary Outcome Measure Information:
Title
Positive and negative symptoms of schizophrenia
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Serum inflammatory markers and cholesterol levels.
Time Frame
12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Raz Gross, M.D., MPH
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sheba Medical Center
City
Ramat Gan
ZIP/Postal Code
52621
Country
Israel
12. IPD Sharing Statement
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Add-on Simvastatin in Schizophrenia Trial
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