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Safety and Efficacy of Aripiprazole and Ziprasidone Among Schizophrenic Patients With Metabolic Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01714011
Recruitment Status : Completed
First Posted : October 25, 2012
Last Update Posted : November 27, 2012
Information provided by (Responsible Party):
University of Malaya

Brief Summary:


Schizophrenia is a serious mental illness. For majority of patients it is a lifetime condition,characterized by intermittent episodes of hospitalization due to relapse or acute symptom exacerbation. The nature and course of the disorder impose significant social and economic burden. Relapse is costly, with hospitalization accounting for a substantial portion of healthcare expenses. Second generation antipsychotic side effect such as metabolic syndrome and diabetes mellitus will contribute additional costs to the treatment.

Many studies have since then provided convincing evidence for a high risk of diabetes and other glucose abnormalities, metabolic syndrome and mortality due to elevated cardiovascular risk in patients with schizophrenia.

However many studies has shown the effectiveness and safety of aripiprazole and ziprazidone.In one of the study, aripiprazole showed improvement of negative schizophrenic symptoms by 25% and 50% of functioning level from baseline. In term of safety, antipsychotics considered to have a safer metabolic profile were amisulpride, ziprasidone and aripiprazole.

Study objectives:

  • To investigate the safety and efficacy of ziprazidone versus aripiprazole in the treatment of schizophrenia patients with metabolic syndrome and diabetes mellitus.
  • To investigate the reversibility of metabolic syndrome and diabetes parameters following the treatment with ziprazidone versus aripiprazole.


* The proportion of reversibility of metabolic syndrome and diabetes parameters is higher following the treatment of ziprazidone than aripiprazole.

Condition or disease Intervention/treatment Phase
Schizophrenia Drug: Ziprasidone Drug: Aripiprazole Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 175 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized Controlled Trial of The Safety and Efficacy of Aripiprazole VS Ziprasidone in Schizophrenic Patients With Metabolic Syndrome and Diabetes Mellitus.
Study Start Date : May 2009
Actual Primary Completion Date : September 2011
Actual Study Completion Date : September 2011

Arm Intervention/treatment
Active Comparator: Ziprasidone
Ziprasidone is a psychotropic agent with chemical name: 5-[2-[4-(1,2-benzisothiazole-3-yl)-1-piperazinyl]ethyl]-6-chloro-1,3-dihydro-2H-indol-2-one.Ziprasidone is a potent antagonist of both serotonin 5-HT2A and dopamine D2 receptors, although its affinity for 5-HT2A receptors is about 10 times higher than for D2 receptors.
Drug: Ziprasidone

Ziprasidone's activity is primarily due to the parent drug. The multiple-dose pharmacokinetics of ziprasidone are dose-proportional within the proposed clinical dose range, and ziprasidone accumulation is predictable with multiple dosing. Elimination of ziprasidone is mainly via hepatic metabolism with a mean terminal half-life of about 7 hours within the proposed clinical dose range.

Steady-state concentrations are achieved within one to three days of dosing. The mean apparent systemic clearance is 7.5 mL/min/kg. Ziprasidone is unlikely to interfere with the metabolism of drugs metabolized by cytochrome P450 enzymes. Ziprasidone is well absorbed after oral administration, reaching peak plasma concentrations in 6 to 8 hours.

Other Name: Zeldox

Active Comparator: Aripiprazole
Aripiprazole is a psychotropic drug that is available as tablets for oral administration. Aripiprazole is 7-[ 4-[ 4-(2,3-dichlorophenyl)-1-piperazinyl]butoxy]-3-4-dihydrocarbostyril. Aripiprazole exhibits high affinity for dopamine D2 and D3, serotonin 5-HT1A and 5-HT2A receptors, moderate affinity for dopamine D4, serotonin 5-HT2C and 5-HT7, alpha 1-adrenergic and histamine H1 receptors and moderate affinity for serotonin reuptake site (Ki = 98nM).
Drug: Aripiprazole
Aripiprazole activity is presumably primarily due to the parent drug, aripiprazole and to a lesser extent, to its major metabolite, dehyrdro-aripiprazole. Steady state concentrations are attained with in 14 days of dosing. The mean elimination half lives are about 75 hours and 95 hours respectively. Elimination of aripiprazole is mainly through hepatic metabolism involving two P450 isozymes, CYP2D6 and CYP3A4. Aripiprazole is well absorbed, with peak plasma concentrations occurring within 3-5 hours; the absolute oral bioavailability of the tablet formulation is 87%. Absorption of aripiprazole is not affected by food.
Other Name: Abilify

Primary Outcome Measures :
  1. Tapering off of previous psychoactive medication. [ Time Frame: 4 weeks ]
    • To taper off previous psychoactive medication gradually.
    • The dosages of either Aripiprazole or Ziprasidone increase gradually until the patient fully switch off to those medications.

Secondary Outcome Measures :
  1. The proportion of reversed metabolic syndrome components among schizophrenia patients after treated with either aripiprazole or ziprasidone [ Time Frame: 6months ]
    • The least squares (LS) mean change of metabolic syndrome parameters among schizophrenia patients after treated with either aripiprazole or ziprasidone.
    • The least squares (LS) mean change of rating scales such as PANNS total, PANSS positive and negative subscales, CGI-S, BAS, SAS, AIMS among schizophrenia patients after treated with either aripiprazole or ziprasidone.
    • To describe all side effects reported by patients during the study.

Other Outcome Measures:
  1. The least squares (LS) mean change of weight and BMI among schizophrenia patients after treated with either aripiprazole or ziprasidone. [ Time Frame: 6 months ]
    To observe patient's parameters such as weight and waist circumference after being treated with ziprasidone or aripiprazole.

  2. Total cholesterol and LDL cholesterol among schizophrenia patients after treated with either aripiprazole or ziprasidone. [ Time Frame: 6 months ]
    • The proportion of cardiovascular risk factors (CVRFs), coronary heart disease (CHD) risk and cardiovascular mortality (CVM) risk among schizophrenia patients after treated with either aripiprazole or ziprasidone.
    • The discontinuation rate between aripiprazole-treated and ziprasidone-treated patients.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Schizophrenic patients
  • Patients with metabolic syndrome
  • Able to provide written informed consent and to comply with all study procedures

Exclusion Criteria:

  • Patient with history of diabetes mellitus prior to the treatment of schizophrenia
  • Neurological or psychiatric disorders, such as depression, bipolar illness, organic brain disease, dementia, or any diseases that require psychotropic medications
  • Serious medical illnesses, including but not limited to; uncontrolled hypertension, significant heart disease (including a history of myocardial infarction, angina, mitral valve prolapse, left ventricular hypertrophy, palpitations, and arrhythmia), hepatic disease, renal disease, or any serious, potentially life-threatening or progressive medical illness that may compromise patient safety or study conduct

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01714011

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University Malaya Medical Centre
Kuala Lumpur, Malaysia, 59100
Sponsors and Collaborators
University of Malaya
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Study Director: Mas Ayu Said, MBBS,MPH University of Malaya
Principal Investigator: Ahmad Hatim Sulaiman, MBBS,MPM University of Malaya

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Responsible Party: University of Malaya Identifier: NCT01714011    
Other Study ID Numbers: MAS001
First Posted: October 25, 2012    Key Record Dates
Last Update Posted: November 27, 2012
Last Verified: November 2012
Keywords provided by University of Malaya:
Metabolic Syndrome
Additional relevant MeSH terms:
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Metabolic Syndrome
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Insulin Resistance
Glucose Metabolism Disorders
Metabolic Diseases
Antidepressive Agents
Psychotropic Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin 5-HT1 Receptor Agonists
Serotonin Receptor Agonists
Serotonin Agents
Serotonin 5-HT2 Receptor Antagonists
Serotonin Antagonists
Dopamine D2 Receptor Antagonists
Dopamine Antagonists