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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Malaya
ClinicalTrials.gov Identifier:
NCT01714011
First received: September 19, 2012
Last updated: November 26, 2012
Last verified: November 2012
  Purpose

Introduction:

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.

Hypotheses:

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


Condition Intervention Phase
Schizophrenia
Drug: Ziprasidone
Drug: Aripiprazole
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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.

Resource links provided by NLM:


Further study details as provided by University of Malaya:

Primary Outcome Measures:
  • Tapering off of previous psychoactive medication. [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    • 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:
  • The proportion of reversed metabolic syndrome components among schizophrenia patients after treated with either aripiprazole or ziprasidone [ Time Frame: 6months ] [ Designated as safety issue: Yes ]
    • 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:
  • The least squares (LS) mean change of weight and BMI among schizophrenia patients after treated with either aripiprazole or ziprasidone. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    To observe patient's parameters such as weight and waist circumference after being treated with ziprasidone or aripiprazole.

  • Total cholesterol and LDL cholesterol among schizophrenia patients after treated with either aripiprazole or ziprasidone. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    • 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.


Enrollment: 175
Study Start Date: May 2009
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01714011

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

No publications provided

Responsible Party: University of Malaya
ClinicalTrials.gov Identifier: NCT01714011     History of Changes
Other Study ID Numbers: MAS001
Study First Received: September 19, 2012
Last Updated: November 26, 2012
Health Authority: Malaysia: Institutional Review Board

Keywords provided by University of Malaya:
Randomized
Controlled
Trial
Safety
Efficacy
Aripiprazole
Ziprasidone
Metabolic Syndrome

Additional relevant MeSH terms:
Metabolic Syndrome X
Schizophrenia
Syndrome
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Disease
Pathologic Processes
Aripiprazole
Ziprasidone
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Dopamine Antagonists
Dopamine Agents

ClinicalTrials.gov processed this record on September 16, 2014