Comparison of Optimal Antipsychotic Treatments for Adults With Schizophrenia

NCT00802100 | Completed Phase 4 Results DMC

• 3 other identifiers: N01 MH090001-02N01MH90001N01MH090001
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 13

Brief Summary

This study will compare the safety and effectiveness of three different antipsychotic medications, as well as the use of other medications to limit treatment side effects, in adults with schizophrenia.

Conditions

Schizophrenia

Keywords

Schizoaffective Disorder

Outcome Measures

Primary Outcomes (1)

• Feasibility of Randomizing a Cohort of Participants Meeting the Inclusion and Exclusion Criteria of the Study

  Goal was to randomize 60 participants who met eligibility criteria.

  Baseline

Secondary Outcomes (1)

• Antipsychotic Efficacy, Defined as Completion of the Trial Without Psychiatric Hospitalization, Clinician Decision to Discontinue Treatment, or Patient Decision to Discontinue Treatment

  Measured over 28 weeks of study visits

Study Arms (3)

Olanzapine

EXPERIMENTAL

Participants will receive treatment with olanzapine and metformin, with the possible addition of simvastatin or benztropine, depending on side effects.

Drug: Olanzapine; Drug: Metformin; Drug: Simvastatin; Drug: Benztropine

Perphenazine

EXPERIMENTAL

Participants will receive treatment with perphenazine and benztropine, with the possible addition of simvastatin or metformin, depending on side effects.

Drug: Perphenazine; Drug: Metformin; Drug: Simvastatin; Drug: Benztropine

Aripiprazole

EXPERIMENTAL

Participants will receive treatment with aripiprazole, with the possible addition of simvastatin, metformin, or benztropine, depending on side effects.

Drug: Aripiprazole; Drug: Metformin; Drug: Simvastatin; Drug: Benztropine

Interventions

Olanzapine DRUG

Daily tablets of 10 to 30 mg

Also known as: Zyprexa

Olanzapine

Perphenazine DRUG

Daily tablets of 8 to 24 mg

Also known as: Trilafon

Perphenazine

Aripiprazole DRUG

Daily tablets of 10 to 30 mg

Also known as: Abilify

Aripiprazole

Metformin DRUG

Daily tablets of 850 to 2550 mg

Also known as: Glucophage

Aripiprazole; Olanzapine; Perphenazine

Simvastatin DRUG

Daily tablets of 20 to 40 mg

Also known as: Zocor

Aripiprazole; Olanzapine; Perphenazine

Benztropine DRUG

Daily tablets of 1 to 2 mg

Also known as: Cogentin

Aripiprazole; Olanzapine; Perphenazine

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis of schizophrenia or schizoaffective disorder, as defined by DSM-IV-TR criteria and confirmed by the Structured Clinical Interview for DSM-IV (SCID)
• Treated with antipsychotic medication for less than 5 years
• Adequate decisional capacity to make a choice about participating in this research study. Adequate decisional capacity will be determined through the aid of a 10-item decisional capacity quiz adapted from the University of California, San Diego, Brief Assessment of Capacity to Consent (UBACC) scale.
• Psychotic exacerbation within the month prior to study entry that required psychiatric hospitalization or an increased level of care
• Willing to use an adequate method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the study. Acceptable methods include oral, injectable, or implanted contraceptives; intrauterine devices; or barrier methods, such as condoms, diaphragm, and spermicides.

You may not qualify if:

• Body mass index at or above 35 kg/m2 or below 18 kg/m2
• Hemoglobin A1c level at or above 7%
• Hematocrit level at or above 31%
• Non-high density lipoprotein cholesterol at or above 190 mg/dL
• Triglycerides at or above 500 mg/dL
• Documented failure, defined as inefficacy or intolerability, with an adequate trial of olanzapine, perphenazine, or aripiprazole. Adequate trials last at least 4 weeks at a minimum dose of 15 mg/day of aripiprazole, 15 mg/day of olanzapine, or 16 mg/day of perphenazine.
• Current treatment with olanzapine, perphenazine, or aripiprazole for more than 1 month
• Known hypersensitivity to metformin, simvastatin, or benztropine
• Treatment with a medication prescribed for weight loss
• Diagnosis of diabetes mellitus or treatment with insulin or other diabetes medication
• Contraindications to metformin use, including any of the following:
• Diagnosis of congestive heart failure
• Renal impairment, defined as serum creatinine at or above 1.5 in males and 1.4 in females, or creatinine estimated glomerular filtration rate (GFR) outside of normal limits
• Hepatic disease, defined as aspartate transaminase (AST), alanine transaminase (ALT), or c-glutamyl transferase (CGT) more than 1.5 times upper limit of normal (ULN) or total bilirubin more than 1.2 times ULN
• Metabolic acidosis, defined as a serum CO2 level less than the lower limit of normal

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (13)

SHANTI Clinical Trials

Colton, California, 92324, United States

Location

Stanford University

Palo Alto, California, 94305, United States

Location

Yale University

New Haven, Connecticut, 06519, United States

Location

University of Miami School of Medicine

Miami, Florida, 33316, United States

Location

Medical College of Georgia

Augusta, Georgia, 30912, United States

Location

Clinical Insights

Glen Burnie, Maryland, 21061, United States

Location

University of Massachusetts

Worcester, Massachusetts, 01605, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

University of Minnesota School of Medicine

Minneapolis, Minnesota, 55454, United States

Location

Research Foundation for Mental Hygiene

New York, New York, 10032, United States

Location

Duke University Medical Center-John Umstead Hospital

Butner, North Carolina, 27509, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75235, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Olanzapine; Perphenazine; Aripiprazole; Metformin; Simvastatin; Benztropine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phenothiazines; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Piperazines; Heterocyclic Compounds, 1-Ring; Quinolones; Quinolines; Biguanides; Guanidines; Amidines; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Tropanes; Azabicyclo Compounds; Aza Compounds; Alkaloids; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Limitations and Caveats

It was determined in this pilot study that the existing procedures and eligibility criteria could not be adequately implemented and that a larger-scale study was not feasible.

Results Point of Contact

• Title: Scott Stroup
• Organization: Columbia University

stroups@nyspi.columbia.edu

(212) 543-5676

Study Officials

• Marvin Swartz, MD

  Duke University

  PRINCIPAL INVESTIGATOR

• T. Scott Stroup, MD, MPH

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

• Joseph P. McEvoy, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2008
• First Posted: December 4, 2008
• Study Start: December 1, 2008
• Primary Completion: September 1, 2009
• Study Completion: October 1, 2009
• Last Updated: February 8, 2013
• Results First Posted: February 8, 2013

Record last verified: 2012-04

Locations

US (13)