Randomized Controlled Trial of The Safety and Efficacy of Aripiprazole VS Ziprasidone in Schizophrenic Patients With Metabolic Syndrome and Diabetes Mellitus.
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- University of Malaya
- Enrollment
- 175
- Locations
- 1
- Primary Endpoint
- Tapering off of previous psychoactive medication.
Study Overview
Brief Summary
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.
Detailed Description
Introduction:
Schizophrenia is a devastating mental illness that impairs mental and social functioning and often leads to the development of comorbid diseases. Metabolic abnormalities have historically been associated with illness such as schizophrenia. 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. These metabolic abnormalities are of major clinical concern not only because of their direct somatic effects on morbidity and mortality but also because of their association with psychiatric outcome, such as a higher prevalence of psychotic and depressive symptoms, a lower functional outcome, a worse perceived physical health, and lower adherence to medication.
Effective pharmacologic treatment of schizophrenia has been available since the 1950s. The first-generation antipsychotics had an increased risk of extrapyramidal side effects, such as dystonic reactions (example, fixed upper gaze, neck twisting, facial muscle spasms), parkinsonian symptoms (example, rigidity, bradykinesia, shuffling gait, tremor), and akathisia (example, inability to sit still, restlessness, tapping of feet).
The term "atypical antipsychotic" refers to newer antipsychotics that confer less risk of extrapyramidal side effects than traditional antipsychotics. Although newer atypical antipsychotics are associated with fewer neurologic side effects, they had a higher risk of metabolic side effects such as diabetes, hypercholesterolemia, and weight gain. This effect is independent from the development of diabetes; the exact mechanism by which atypical agents might cause diabetes is unknown. Few drugs such as aripiprazole, sertindole, amisulpride and ziprasidone were found to have promising effect in lowering metabolic syndrome.
The study is designed to:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- 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
Arms & Interventions
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.
Intervention: Ziprasidone (Drug)
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).
Intervention: Aripiprazole (Drug)
Outcomes
Primary Outcomes
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 Outcomes
- The proportion of reversed metabolic syndrome components among schizophrenia patients after treated with either aripiprazole or ziprasidone(6months)