Aripiprazole as an Adjunct to Atypical Antipsychotics for Weight Reduction and Improvement in Metabolic Profile
Primary Purpose
Antipsychotics Weight Gain
Status
Completed
Phase
Phase 4
Locations
Singapore
Study Type
Interventional
Intervention
Aripiprazole
Sponsored by
About this trial
This is an interventional treatment trial for Antipsychotics Weight Gain
Eligibility Criteria
Inclusion Criteria:
- Adult male or female patients (21 to 65 yrs)
- Diagnosis of Schizophrenia or Schizoaffective Disorder
- Outpatients
- On stable doses of atypical antipsychotics, either Olanzapine, Clozapine, or Risperidone for at least 1 month
- Patients can be on other concomitant medications. Patients can be on antipsychotic polypharmacy, but there should not be more than 1 of the above 3 atypicals in a single prescription.
- Patients should be able to provide written informed consent.
- Currently with a BMI ≥ 25 (Overweight) and/or ≥7% increase in weight from pre-antipsychotic treatment.
Exclusion Criteria:
- Previous allergy to Aripiprazole/contraindication to use of Aripiprazole
- Participants with current substance misuse, including alcohol but excluding tobacco.
- Non-compliant with prescribed medications
- Mental Retardation
- Presence of any major or unstable medical or neurological illness (such as uncontrolled diabetes and hypertension).
- Participant with an eating disorder
- Participants with serious suicidal thoughts, or who pose a serious risk of harm to self or to others.
- Women who are pregnant or breastfeeding
- Severe Personality Disorder
- Diagnosis of Hyper or Hypothyroidism; Evidence of thyroid dysfunction as evidenced by serum thyroid function tests (i.e Thyroid Stimulating Hormone and Free Thyroxine (fT4) levels > 10 % above or below the limits of the normal range
- Use of any medication for weight loss within the past one month to the study entry
- Clinically significant abnormalities in physical examinations, ECG or lab assessments
- Baseline BMI < 18.5kg/m2 (cut-off point for underweight adults as per World Health Organisation guidelines)
- Unable to read or speak English
Sites / Locations
- Institute of Mental Health
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Aripiprazole Adjunct
Arm Description
Aripiprazole 5 mg as a fixed dose as adjunct to other antipsychotics
Outcomes
Primary Outcome Measures
Mean change in body weight in kilograms
To assess mean change in body weight from baseline to week 12 in patients receiving adjunctive Aripiprazole to atypical antipsychotic therapy, i.e. olanzapine, clozapine, risperidone.
Secondary Outcome Measures
Change in waist circumference in cm
To evaluate change in waist circumference from baseline to week 12
Number of participants with treatment-related adverse events as assessed by Side Effects Checklist
To evaluate safety and tolerability data on adjunctive use of Aripiprazole using side effect checklist
Number of participants with improvement or deterioration in neuro-cognition as assessed by Digit Sequencing Test and Symbol Coding Test
To evaluate changes in neuro-cognition from baseline to week 12
Change in fasting plasma glucose mg/dl from baseline to week 12
To evaluate change in fasting plasma glucose mg/dl from baseline to week 12
Change in Total Cholesterol, LDL and HDL Cholesterol mg/dl from baseline to week 12
Change in HbA1c (%) from baseline to week 12
Full Information
NCT ID
NCT02949752
First Posted
October 4, 2016
Last Updated
July 19, 2021
Sponsor
Institute of Mental Health, Singapore
1. Study Identification
Unique Protocol Identification Number
NCT02949752
Brief Title
Aripiprazole as an Adjunct to Atypical Antipsychotics for Weight Reduction and Improvement in Metabolic Profile
Official Title
Aripiprazole as an Adjunct to Atypical Antipsychotics for Weight Reduction and Improvement in Metabolic Profile
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
August 2016 (Actual)
Primary Completion Date
October 1, 2019 (Actual)
Study Completion Date
January 1, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Institute of Mental Health, Singapore
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is an open label study to prospectively evaluate the effect of adjunct use of Aripiprazole, as an agent to improve metabolic profile and induce weight loss in patients established on atypical antipsychotics (Olanzapine, Clozapine and Risperidone).
Detailed Description
The metabolic syndrome (MetS) is a well described cluster of interrelated risk factors for developing cardiovascular disease and type 2 diabetes. The main components of MetS are central obesity, hypertension, hyperglycaemia and dyslipidaemia. Individuals with MetS are two to three times more likely to have a heart attack or stroke and five times more likely to develop type 2 diabetes than those without. Metabolic abnormalities have often been identified in individuals with schizophrenia. Since the introduction of second generation antipsychotics, evidence has accumulated of their link with metabolic abnormalities. An abnormality in glucose metabolism, particularly diabetes mellitus (DM), has received the most attention. Other conditions such as cardiovascular morbidity, abnormal lipid metabolism and obesity also have a serious impact on the physical health of individuals with schizophrenia. Several pharmacological strategies are under investigation for countering the metabolic side effects, of which antipsychotic Aripiprazole has shown good evidence, when switched to as monotherapy, and also as an adjunct .
The study is planned as an open label study. An open label exploratory design will help test the hypothesis that use of adjunct Aripiprazole can help with reducing weight gain on atypical antipsychotics, and improve metabolic parameters. The number of patients in each arm is designed to yield an 80% power to detect significant differences in weight from baseline at P<0.05. There is no randomisation, blinding or placebo control, as this study is planned to test the initial hypothesis, which can inform further RCT's, if results are encouraging.
Participants will initially be screened to ensure that they fulfil the inclusion criterion, and eligible participants will be entered into the 12 week study, where they will be prescribed 5 mg Aripiprazole per day, in addition to their routine atypical antipsychotic. The typical dose range of the routine atypical antipsychotics are clozapine 200-450 mg, olanzapine 5-20mg and risperidone 2-16mg respectively. During the 12 week study, the dose of the antipsychotic and Aripiprazole should stay unchanged. If the clinical situation warrants a change in dose of antipsychotic or switch of antipsychotic, the participant will be withdrawn from the study. Atypical antipsychotic other than the ones under investigation will be prohibited, as well as medications or supplements for weight loss or weight gain, or medications known to have substantial propensity for weight changes. Benzodiazepines, anticholinergics, sleep aides will generally be allowed. Antidepressants and mood stabilisers at a stable dose, which patients were receiving prior to the study, will be allowed. Patients at high risk of suicide or self-harm as assessed by the study investigator, will be withdrawn from the study, as well as those with significant side effects from adjunct Aripiprazole.
The primary objective of the study is to assess mean change of weight from the baseline after use of adjunct Aripiprazole. The secondary endpoints include changes in metabolic parameters (waist circumference, fasting blood glucose, HbA1c, total, HDL and LDL cholesterol levels).Safety and tolerability will be measured by Simpson Angus Scale (SAS total score), Side Effects Checklist, Barnes Akathisia Scale (BAS), Abnormal Involuntary Movement Scale (AIMS), adverse events or serious adverse events reports.
The study will also evaluate neurocognition via a brief battery of 2 tests - the digit sequencing and symbol coding. These 2 tasks have been shown in a previous study to explain 76% of the variance of global neurocognition in a large sample of patients with schizophrenia. In our local sample, it was similarly shown that these 2 tasks are valid, representing 72% of the variance in global neurocognition in schizophrenia (unpublished results). The avoidance of a language component in these 2 tasks is a significant strength in choice of cognitive tasks as has been previously shown that the local population tend to underperform on language-based cognitive tasks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Antipsychotics Weight Gain
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
67 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Aripiprazole Adjunct
Arm Type
Experimental
Arm Description
Aripiprazole 5 mg as a fixed dose as adjunct to other antipsychotics
Intervention Type
Drug
Intervention Name(s)
Aripiprazole
Intervention Description
Aripiprazole 5 mg every morning will be prescribed for 12 weeks
Primary Outcome Measure Information:
Title
Mean change in body weight in kilograms
Description
To assess mean change in body weight from baseline to week 12 in patients receiving adjunctive Aripiprazole to atypical antipsychotic therapy, i.e. olanzapine, clozapine, risperidone.
Time Frame
12 weeks, assessed at baseline and at final follow up at week 12
Secondary Outcome Measure Information:
Title
Change in waist circumference in cm
Description
To evaluate change in waist circumference from baseline to week 12
Time Frame
12 weeks, assessed at baseline and at final follow up at week 12
Title
Number of participants with treatment-related adverse events as assessed by Side Effects Checklist
Description
To evaluate safety and tolerability data on adjunctive use of Aripiprazole using side effect checklist
Time Frame
Checklist completed every two weeks, for the study duration of 12 weeks via Face to Face interview or Telephone contact
Title
Number of participants with improvement or deterioration in neuro-cognition as assessed by Digit Sequencing Test and Symbol Coding Test
Description
To evaluate changes in neuro-cognition from baseline to week 12
Time Frame
12 weeks, assessed at baseline and at final follow up at week 12
Title
Change in fasting plasma glucose mg/dl from baseline to week 12
Description
To evaluate change in fasting plasma glucose mg/dl from baseline to week 12
Time Frame
12 weeks, assessed at baseline and at final follow up at week 12
Title
Change in Total Cholesterol, LDL and HDL Cholesterol mg/dl from baseline to week 12
Time Frame
12 weeks, assessed at baseline and at final follow up at week 12
Title
Change in HbA1c (%) from baseline to week 12
Time Frame
12 weeks, assessed at baseline and at final follow up at week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult male or female patients (21 to 65 yrs)
Diagnosis of Schizophrenia or Schizoaffective Disorder
Outpatients
On stable doses of atypical antipsychotics, either Olanzapine, Clozapine, or Risperidone for at least 1 month
Patients can be on other concomitant medications. Patients can be on antipsychotic polypharmacy, but there should not be more than 1 of the above 3 atypicals in a single prescription.
Patients should be able to provide written informed consent.
Currently with a BMI ≥ 25 (Overweight) and/or ≥7% increase in weight from pre-antipsychotic treatment.
Exclusion Criteria:
Previous allergy to Aripiprazole/contraindication to use of Aripiprazole
Participants with current substance misuse, including alcohol but excluding tobacco.
Non-compliant with prescribed medications
Mental Retardation
Presence of any major or unstable medical or neurological illness (such as uncontrolled diabetes and hypertension).
Participant with an eating disorder
Participants with serious suicidal thoughts, or who pose a serious risk of harm to self or to others.
Women who are pregnant or breastfeeding
Severe Personality Disorder
Diagnosis of Hyper or Hypothyroidism; Evidence of thyroid dysfunction as evidenced by serum thyroid function tests (i.e Thyroid Stimulating Hormone and Free Thyroxine (fT4) levels > 10 % above or below the limits of the normal range
Use of any medication for weight loss within the past one month to the study entry
Clinically significant abnormalities in physical examinations, ECG or lab assessments
Baseline BMI < 18.5kg/m2 (cut-off point for underweight adults as per World Health Organisation guidelines)
Unable to read or speak English
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bhanu Gupta, MRCPsych
Organizational Affiliation
Institute of Mental Health, Singapore
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institute of Mental Health
City
Singapore
ZIP/Postal Code
556121
Country
Singapore
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
20459883
Citation
Fleischhacker WW, Heikkinen ME, Olie JP, Landsberg W, Dewaele P, McQuade RD, Loze JY, Hennicken D, Kerselaers W. Effects of adjunctive treatment with aripiprazole on body weight and clinical efficacy in schizophrenia patients treated with clozapine: a randomized, double-blind, placebo-controlled trial. Int J Neuropsychopharmacol. 2010 Sep;13(8):1115-25. doi: 10.1017/S1461145710000490. Epub 2010 May 12.
Results Reference
background
PubMed Identifier
34646440
Citation
Gupta B, Chee KS, Neo LQ, Tang C, Hariram J, Tan GC, Verma S, Basu S, Appan DP, Ting CC, Abdin E, Lee J. Effect of aripiprazole as an adjunct to atypical antipsychotics on weight and metabolic profile: a 12-week open-label trial. Ther Adv Psychopharmacol. 2021 Oct 9;11:20451253211046765. doi: 10.1177/20451253211046765. eCollection 2021.
Results Reference
derived
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Aripiprazole as an Adjunct to Atypical Antipsychotics for Weight Reduction and Improvement in Metabolic Profile
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