Safety and Efficacy of Aripiprazole and Ziprasidone Among Schizophrenic Patients With Metabolic Syndrome
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|ClinicalTrials.gov Identifier: NCT01714011|
Recruitment Status : Completed
First Posted : October 25, 2012
Last Update Posted : November 27, 2012
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.
- 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|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||175 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Outcomes Assessor)|
|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|
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.
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).
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
- 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.
- 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.
- 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.
- 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.
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 ClinicalTrials.gov identifier (NCT number): NCT01714011
|University Malaya Medical Centre|
|Kuala Lumpur, Malaysia, 59100|
|Study Director:||Mas Ayu Said, MBBS,MPH||University of Malaya|
|Principal Investigator:||Ahmad Hatim Sulaiman, MBBS,MPM||University of Malaya|