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MEAC: Metabolic Effects of Antipsychotics in Children

Sponsor
Washington University School of Medicine (Other)
Overall Status
Completed
CT.gov ID
NCT00205699
Collaborator
National Institute of Mental Health (NIMH) (NIH)
144
Enrollment
1
Location
3
Arms
63
Actual Duration (Months)
2.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The project aims to describe and compare the outcome of 12 weeks of prospective, randomized treatment with olanzapine, risperidone or aripiprazole on insulin action in skeletal muscle, liver and adipose tissue, abdominal fat mass, total body and fat-free mass, efficacy for symptoms of aggression and non-metabolic adverse events. Children aged 6-18 will be studied, exploring effects of stimulant therapy and age-related differences in vulnerability to treatment-induced adverse metabolic changes. Aims are addressed by measuring glucose and lipid kinetics with stable isotope tracers, body composition with dual energy x-ray absorptiometry and magnetic resonance imaging (MRI), and standardized assessments of efficacy and adverse events. Relevant data are critically needed to target clinical therapy and basic research, identify medical risks, and guide regulatory decisions in this vulnerable population.

Condition or Disease Intervention/Treatment Phase
Phase 4

Detailed Description

This randomized clinical trial assesses both the safety and efficacy of atypical antipsychotic agents in antipsychotic-naive aggressive children with various childhood psychiatric disorders during 12 weeks of prospective, randomized treatment with olanzapine, risperidone or aripiprazole.

Aim 1: To evaluate effects of selected antipsychotic treatments on insulin action in muscle (glucose disposal), liver (glucose production) and adipose tissue (lipolysis).

Aim 2: To evaluate effects of selected antipsychotic treatments on abdominal fat mass, total body fat and total fat-free mass.

Study Design

Study Type:
Interventional
Actual Enrollment :
144 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Metabolic Effects of Antipsychotics in Children
Actual Study Start Date :
Apr 1, 2006
Actual Primary Completion Date :
Mar 1, 2011
Actual Study Completion Date :
Jul 1, 2011

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: aripiprazole

Participants in this group will be randomized to flexibly-dosed treatment with aripiprazole.

Drug: aripiprazole
randomized to 12 week trial of aripiprazole
Other Names:
  • Abilify

    		•
    Active Comparator: olanzapine

    Participants in this group will be randomized to flexibly-dosed treatment with olanzapine.

    Drug: olanzapine
    randomized to begin 12 week trial of olanzapine
    Other Names:
  • Zyprexa

    		•
    Active Comparator: risperidone

    Participants in this group will be randomized to flexibly-dosed treatment with risperidone.

    Drug: risperidone
    randomized to begin 12 week trial of risperidone
    Other Names:
  • Risperdal

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change in DEXA % Body Fat [12 weeks]

      This study hypothesized that antipsychotic treatment would increase percent total body fat, as measured by whole body dual energy x-ray absorptiometry (DEXA), with larger adverse effects for olanzapine.

    2. Change in Insulin-stimulated Glucose Rate of Disappearance (Glucose Rd) [12 weeks]

      This study hypothesized that antipsychotic treatment would decrease insulin sensitivity at muscle, as measured by the insulin-stimulated rate of disappearance of glucose (glucose Rd), with larger adverse effects for olanzapine.

    Secondary Outcome Measures

    1. Change in Insulin-stimulated Glycerol Rate of Appearance (Glycerol Ra) [12 weeks]

      This study hypothesized that antipsychotic treatment would decrease insulin sensitivity at adipose tissue, as measured by the insulin-stimulated rate of disappearance of glycerol (glycerol Ra), with larger adverse effects for olanzapine.

    2. Change in Insulin-stimulated Glucose Rate of Appearance (Glucose Ra) [12 weeks]

      This study hypothesized that antipsychotic treatment would decrease hepatic insulin sensitivity, as measured by the rate of appearance of glucose (glucose Ra), with larger adverse effects for olanzapine.

    3. Change in MRI-measured Visceral Abdominal Fat [12 weeks]

      This study hypothesized that antipsychotic treatment would increase visceral abdominal fat, as measured by abdominal magnetic resonance imaging (MRI), with larger adverse effects for olanzapine.

    4. Change in MRI-measured Subcutaneous Abdominal Fat [12 weeks]

      This study hypothesized that antipsychotic treatment would increase subcutaneous abdominal fat, as measured by abdominal magnetic resonance imaging (MRI), with larger adverse effects for olanzapine.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    6 Years to 18 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Aged 6-18 years

    • Generally healthy and a score of ≥ 18 on the Aberrant Behavior Checklist in the context of one or more Axis I Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) childhood psychiatric disorders, including conduct disorder, oppositional defiant disorder, disruptive behavior disorder, autism, pervasive developmental disorder, attention deficit disorder, schizophrenia and bipolar affective disorders

    • Children's Global Assessment Scale (CGAS) score ≤ 60

    • Not previously treated with an antipsychotic; individual subjects with remote, brief prior antipsychotic exposure may be considered for enrollment by the PI on a case by case basis

    • Patient assent and informed consent obtained from the parent or guardian

    • No clinically significant (based on PI determination) changes in permitted medications (e.g., stimulants and selective serotonin reuptake inhibitors [SSRIs]) for approximately 1 month prior to Baseline evaluations

    Exclusion Criteria:

    • Active suicidality or primary dx of major depressive disorder

    • Any lifetime use of antipsychotics or non-serotonin selective reuptake inhibitor (non-SSRI) anti-depressants

    • The presence of any serious medical disorder, based on PI determination, that may confound the assessment of relevant biologic measures or diagnoses, including:

    • significant organ system dysfunction;

    • endocrine disease, including type 1 or type 2 diabetes mellitus;

    • coagulopathy;

    • anemia;

    • or acute infection.

    • Subjects regularly taking any glucose lowering agent, lipid lowering agent, exogenous testosterone, recombinant human growth hormone, or any other endocrine agent that might confound substrate metabolism, oral glucocorticoids (glucocorticoid inhalants and nasal sprays are permitted), antihistamines, sedating antihistamines (non-sedating antihistamines such as but not limited to Claritin (loratadine) and Zyrtec (cetirizine) are permitted), and certain mood stabilizing agents, as some medications may themselves worsen or otherwise alter weight gain, glucose and lipid regulation or otherwise make it difficult to assess the effects of the antipsychotic alone; (note that exposure to many psychotropic agents including stimulants and SSRI's is permitted in order to maintain the generalizability of the sample);

    • Intelligence quotient (IQ) < 70 (based on school records and/or evaluation by clinician)

    • current substance abuse

    • Past history or currently has dyskinesia

    • Stimulant dosage significantly higher (per PI judgment)than the equivalent of approximately 2mg/kg/day methylphenidate equivalent dose.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Washington University School of Medicine, Psychiatry Dept. Saint Louis Missouri United States 63110

    Sponsors and Collaborators

    • Washington University School of Medicine
    • National Institute of Mental Health (NIMH)

    Investigators

    • Principal Investigator: John W. Newcomer, MD, Florida Atlantic University and Washington University School of Medicine
    • Study Director: Ginger Nicol, MD, Washington University School of Medicine

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Washington University School of Medicine
    ClinicalTrials.gov Identifier:
    NCT00205699
    Other Study ID Numbers:
    • NIMH
    • R01MH072912
    First Posted:
    Sep 20, 2005
    Last Update Posted:
    Jun 15, 2018
    Last Verified:
    Jun 1, 2018
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Keywords provided by Washington University School of Medicine
    Antipsychotic treatment
    Insulin action/secretion
    Abdominal fat mass, total body fat
    Aggression
    Resting metabolic rates
    Additional relevant MeSH terms:
    Disease
    Bipolar Disorder
    Aggression
    Attention Deficit and Disruptive Behavior Disorders
    Child Development Disorders, Pervasive
    Autism Spectrum Disorder
    Olanzapine
    Risperidone
    Aripiprazole

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Post-enrollment screening for inclusion and exclusion criteria, e.g. for exclusionary conditions like diabetes mellitus.
    Arm/Group Title Risperidone Olanzapine Aripiprazole
    Arm/Group Description 12 weeks of randomized treatment with flexibly dosed risperidone 12 weeks of randomized treatment with flexibly dosed olanzapine 12 weeks of randomized treatment with flexibly dosed aripiprazole
    Period Title: Overall Study
    STARTED 49 46 49
    COMPLETED 46 40 43
    NOT COMPLETED 3 6 6

    Baseline Characteristics

    Arm/Group Title Risperidone Olanzapine Aripiprazole Total
    Arm/Group Description 12 weeks randomized, flexibly-dosed treatment with risperidone 12 weeks randomized, flexibly-dosed treatment with olanzapine 12 weeks randomized, flexibly-dosed treatment with aripiprazole Total of all reporting groups
    Overall Participants 49 46 49 144
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    11.32
    (2.95)
    11.10
    (2.52)
    11.60
    (2.92)
    11.35
    (2.79)
    Sex: Female, Male (Count of Participants)
    Female
    13
    26.5%
    18
    39.1%
    15
    30.6%
    46
    31.9%
    Male
    36
    73.5%
    28
    60.9%
    34
    69.4%
    98
    68.1%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    2
    4.1%
    1
    2.2%
    1
    2%
    4
    2.8%
    Not Hispanic or Latino
    47
    95.9%
    45
    97.8%
    48
    98%
    140
    97.2%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race/Ethnicity, Customized (participants) [Number]
    White
    24
    49%
    22
    47.8%
    19
    38.8%
    65
    45.1%
    Non-White
    25
    51%
    24
    52.2%
    30
    61.2%
    79
    54.9%
    Primary Diagnosis (participants) [Number]
    Attention Deficit Hyperactivity Disorder
    28
    57.1%
    23
    50%
    29
    59.2%
    80
    55.6%
    Disruptive Behavior Disorder
    8
    16.3%
    11
    23.9%
    13
    26.5%
    32
    22.2%
    Mood Disorder
    7
    14.3%
    5
    10.9%
    4
    8.2%
    16
    11.1%
    Autism Spectrum Disorder
    3
    6.1%
    4
    8.7%
    3
    6.1%
    10
    6.9%
    Psychosis
    2
    4.1%
    2
    4.3%
    0
    0%
    4
    2.8%
    Obsessive Compulsive Disorder
    0
    0%
    1
    2.2%
    0
    0%
    1
    0.7%
    Tourette Disorder
    1
    2%
    0
    0%
    0
    0%
    1
    0.7%
    Clinical Global Improvement (CGI)-Severity of Illness (participants) [Number]
    Moderately ill
    18
    36.7%
    19
    41.3%
    23
    46.9%
    60
    41.7%
    Markedly ill
    31
    63.3%
    26
    56.5%
    23
    46.9%
    80
    55.6%
    Severely ill
    0
    0%
    1
    2.2%
    3
    6.1%
    4
    2.8%
    Aberrant Behavioral Checklist Subscales (units on a scale) [Mean (Standard Deviation) ]
    Total
    88.03
    (23.96)
    81.89
    (21.55)
    83.53
    (25.70)
    84.54
    (23.82)
    Irritability/Aggression
    28.49
    (5.53)
    28.17
    (5.73)
    28.14
    (6.27)
    28.27
    (5.81)
    Lethargy
    16.57
    (10.01)
    12.67
    (8.15)
    14.61
    (8.83)
    14.66
    (9.12)
    Stereotypy
    5.54
    (4.95)
    5.15
    (4.42)
    4.29
    (4.61)
    4.99
    (4.67)
    Hyperactivity
    32.83
    (9.68)
    32.11
    (10.45)
    32.80
    (10.88)
    32.59
    (10.28)
    Inappropriate Speech
    4.60
    (3.02)
    3.78
    (2.71)
    3.69
    (2.76)
    4.03
    (2.85)
    Clinical Global Assessment of Functioning (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    51.71
    (4.44)
    50.67
    (5.44)
    50.88
    (6.00)
    51.10
    (5.31)
    Number of Suspensions (number of discrete school suspensions) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [number of discrete school suspensions]
    2.60
    (4.11)
    2.71
    (3.98)
    2.85
    (4.18)
    2.72
    (4.07)
    On stimulant (participants) [Number]
    Yes
    29
    59.2%
    21
    45.7%
    22
    44.9%
    72
    50%
    No
    20
    40.8%
    25
    54.3%
    27
    55.1%
    72
    50%
    On Selective Serotonin Reuptake Inhibitors (SSRI) (participants) [Number]
    Yes
    8
    16.3%
    5
    10.9%
    4
    8.2%
    17
    11.8%
    No
    41
    83.7%
    41
    89.1%
    45
    91.8%
    127
    88.2%
    DEXA-measured body composition (%) (percentage of body composition) [Mean (Standard Deviation) ]
    DEXA Total % Fat
    26.25
    (10.64)
    24.48
    (10.19)
    26.23
    (10.83)
    25.68
    (10.52)
    DEXA Total % Lean
    70.30
    (10.35)
    71.96
    (9.96)
    70.32
    (10.53)
    70.84
    (10.25)
    DEXA-measured body composition (kg) (kilograms) [Mean (Standard Deviation) ]
    DEXA Total Fat kg
    12.50
    (9.53)
    10.46
    (6.68)
    13.24
    (10.40)
    12.10
    (9.07)
    DEXA Total Lean kg
    30.38
    (11.01)
    29.30
    (9.83)
    31.98
    (14.69)
    30.58
    (12.04)
    Baseline Insulin Stimulated % Change in Isotopomer Measurement during Week 0 Clamp (% change during baseline clamp) [Mean (Standard Deviation) ]
    % Change in Glucose Rate of Disappearance
    166.26
    (78.79)
    168.75
    (82.09)
    156.49
    (81.14)
    163.56
    (80.06)
    % Change in Glucose Rate of Appearance
    83.19
    (10.94)
    82.53
    (9.90)
    82.70
    (12.15)
    82.83
    (11.01)
    % Change in Glycerol Rate of Appearance
    55.59
    (13.42)
    55.94
    (15.08)
    50.46
    (15.04)
    53.89
    (14.59)
    Whole Body Sensitivity
    12.96
    (5.33)
    12.53
    (4.47)
    12.87
    (6.36)
    12.80
    (5.44)
    MRI-measured abdominal fat (cm squared) [Mean (Standard Deviation) ]
    MRI Subcutaneous Fat
    121.38
    (123.05)
    86.17
    (65.10)
    111.16
    (94.16)
    107.23
    (98.53)
    MRI Visceral Fat
    25.79
    (18.45)
    19.37
    (19.74)
    26.70
    (24.14)
    24.11
    (20.96)
    MRI Total Fat
    147.17
    (137.36)
    106.09
    (82.28)
    137.85
    (116.24)
    131.56
    (115.76)
    Body Weight (kilograms) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kilograms]
    45.49
    (19.08)
    42.23
    (13.81)
    47.94
    (23.57)
    45.28
    (19.34)
    Waist Circumference (centimeters) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [centimeters]
    68.72
    (13.47)
    65.87
    (11.03)
    69.54
    (15.50)
    68.09
    (13.50)
    Body Mass Index Percentile (percentile) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [percentile]
    62.13
    (29.70)
    58.38
    (31.33)
    63.05
    (30.12)
    61.25
    (30.22)
    Body Mass index z-score (z-score) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [z-score]
    0.49
    (1.12)
    0.30
    (1.11)
    0.55
    (1.13)
    0.45
    (1.12)
    Baseline fasting laboratory values (mg/dL) (mg/dL) [Mean (Standard Deviation) ]
    Fasting Glucose
    89.14
    (8.81)
    87.48
    (6.55)
    88.98
    (6.16)
    88.56
    (7.27)
    Total Cholesterol
    144.74
    (28.88)
    137.09
    (25.31)
    135.45
    (28.34)
    139.14
    (27.71)
    Triglycerides
    60.40
    (33.00)
    60.98
    (31.89)
    52.16
    (23.13)
    57.78
    (29.69)
    LDL Cholesterol
    79.53
    (25.41)
    72.00
    (24.56)
    72.82
    (26.00)
    74.84
    (25.40)
    Total Bilirubin
    0.37
    (0.25)
    0.40
    (0.18)
    0.33
    (0.18)
    0.37
    (0.21)
    Baseline Fasting Laboratory Values (IU/L) (IU/L) [Mean (Standard Deviation) ]
    Alanine aminotransferase (ALT)
    18.10
    (7.74)
    13.83
    (4.20)
    15.53
    (4.49)
    15.86
    (5.96)
    Aspartate aminostransferase (AST)
    25.65
    (7.10)
    23.26
    (6.12)
    23.94
    (6.78)
    24.31
    (6.72)
    Alkaline Phosphatase
    209.33
    (88.42)
    222.54
    (75.69)
    206.41
    (85.35)
    212.56
    (83.19)
    Baseline fasting laboratory values (g/dL) (g/dL) [Mean (Standard Deviation) ]
    Albumin
    4.02
    (0.25)
    4.06
    (0.27)
    4.05
    (0.25)
    4.05
    (0.25)
    Total Protein
    6.95
    (0.46)
    6.90
    (0.39)
    6.95
    (0.34)
    6.94
    (0.40)
    High Sensitivity c-Reactive Protein (HS-CRP) (mg/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/L]
    1.61
    (3.04)
    1.37
    (3.04)
    1.12
    (1.53)
    1.37
    (2.62)
    Fasting Insulin (uU/mL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [uU/mL]
    7.64
    (5.85)
    6.24
    (3.74)
    9.00
    (8.68)
    7.65
    (6.50)
    Hemoglobin A1c (%) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [%]
    5.46
    (0.26)
    5.54
    (0.34)
    5.54
    (0.28)
    5.52
    (0.29)

    Outcome Measures

    1. Primary Outcome
    Title Change in DEXA % Body Fat
    Description This study hypothesized that antipsychotic treatment would increase percent total body fat, as measured by whole body dual energy x-ray absorptiometry (DEXA), with larger adverse effects for olanzapine.
    Time Frame 12 weeks

    Outcome Measure Data

    Analysis Population Description
    Modified Intent to Treat (ITT) sample with week 0 and week 12 data.
    Arm/Group Title Risperidone Olanzapine Aripiprazole
    Arm/Group Description 12 weeks randomized, flexibly-dosed treatment with risperidone 12 weeks randomized, flexibly-dosed treatment with olanzapine 12 weeks randomized, flexibly-dosed treatment with aripiprazole
    Measure Participants 46 40 42
    Mean (Standard Deviation) [percent body fat]
    1.81
    (3.11)
    4.12
    (3.10)
    1.66
    (2.65)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Risperidone, Olanzapine, Aripiprazole
    Comments Primary analysis for change in DEXA % fat used a likelihood-based mixed-effects model using time (0, 6 and 12 weeks) and medication group as independent variables, with Toeplitz covariance structure specified, based on Bayesian information criteria (BIC). The null hypotheses were that there was no difference in the outcome over time (main effect of time) and that there were no differences between groups in the change over time (time by treatment condition).
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments The p value refers to the time by treatment condition interaction. The a priori threshold for statistical significance in this planned primary test was p<0.05.
    Method Mixed Models Analysis
    Comments
    2. Primary Outcome
    Title Change in Insulin-stimulated Glucose Rate of Disappearance (Glucose Rd)
    Description This study hypothesized that antipsychotic treatment would decrease insulin sensitivity at muscle, as measured by the insulin-stimulated rate of disappearance of glucose (glucose Rd), with larger adverse effects for olanzapine.
    Time Frame 12 weeks

    Outcome Measure Data

    Analysis Population Description
    Children ages 6-18 with a Diagnostic and Statistical Manual Text Revision (DSM-IV-TR) diagnosis and clinically significant aggression or irritability
    Arm/Group Title Risperidone Olanzapine Aripiprazole
    Arm/Group Description 12 weeks randomized, flexibly-dosed treatment with risperidone 12 weeks randomized, flexibly-dosed treatment with olanzapine 12 weeks randomized, flexibly-dosed treatment with aripiprazole
    Measure Participants 39 33 40
    Mean (Standard Deviation) [percentage of % change]
    2.30
    (83.91)
    -29.34
    (85.56)
    -30.26
    (65.46)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Risperidone, Olanzapine, Aripiprazole
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.07
    Comments
    Method ANCOVA
    Comments
    3. Secondary Outcome
    Title Change in Insulin-stimulated Glycerol Rate of Appearance (Glycerol Ra)
    Description This study hypothesized that antipsychotic treatment would decrease insulin sensitivity at adipose tissue, as measured by the insulin-stimulated rate of disappearance of glycerol (glycerol Ra), with larger adverse effects for olanzapine.
    Time Frame 12 weeks

    Outcome Measure Data

    Analysis Population Description
    Modified Intent to Treat (ITT) sample with week 0 and week 12 data.
    Arm/Group Title Risperidone Olanzapine Aripiprazole
    Arm/Group Description 12 weeks of randomized treatment with flexibly dosed risperidone 12 weeks of randomized treatment with flexibly dosed olanzapine 12 weeks of randomized treatment with flexibly dosed aripiprazole
    Measure Participants 38 31 39
    Mean (Standard Deviation) [percentage of % change]
    -3.65
    (17.23)
    -8.29
    (22.39)
    1.70
    (16.79)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Risperidone, Olanzapine, Aripiprazole
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.27
    Comments
    Method ANCOVA
    Comments
    4. Secondary Outcome
    Title Change in Insulin-stimulated Glucose Rate of Appearance (Glucose Ra)
    Description This study hypothesized that antipsychotic treatment would decrease hepatic insulin sensitivity, as measured by the rate of appearance of glucose (glucose Ra), with larger adverse effects for olanzapine.
    Time Frame 12 weeks

    Outcome Measure Data

    Analysis Population Description
    Modified Intent to Treat (ITT) sample with week 0 and week 12 data.
    Arm/Group Title Risperidone Olanzapine Aripiprazole
    Arm/Group Description 12 weeks of randomized treatment with flexibly dosed risperidone 12 weeks of randomized treatment with flexibly dosed olanzapine 12 weeks of randomized treatment with flexibly dosed aripiprazole
    Measure Participants 39 33 40
    Mean (Standard Deviation) [percentage of % change]
    -2.50
    (7.61)
    -6.57
    (13.16)
    -3.27
    (9.27)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Risperidone, Olanzapine, Aripiprazole
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.17
    Comments
    Method ANCOVA
    Comments
    5. Secondary Outcome
    Title Change in MRI-measured Visceral Abdominal Fat
    Description This study hypothesized that antipsychotic treatment would increase visceral abdominal fat, as measured by abdominal magnetic resonance imaging (MRI), with larger adverse effects for olanzapine.
    Time Frame 12 weeks

    Outcome Measure Data

    Analysis Population Description
    Modified Intent to Treat (ITT) sample with week 0 and week 12 data.
    Arm/Group Title Risperidone Olanzapine Aripiprazole
    Arm/Group Description 12 weeks of randomized treatment with flexibly dosed risperidone 12 weeks of randomized treatment with flexibly dosed olanzapine 12 weeks of randomized treatment with flexibly dosed aripiprazole
    Measure Participants 30 26 30
    Mean (Standard Deviation) [Change in cm-squared]
    6.85
    (10.99)
    10.73
    (14.50)
    12.04
    (15.11)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Risperidone, Olanzapine, Aripiprazole
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.29
    Comments
    Method ANCOVA
    Comments
    6. Secondary Outcome
    Title Change in MRI-measured Subcutaneous Abdominal Fat
    Description This study hypothesized that antipsychotic treatment would increase subcutaneous abdominal fat, as measured by abdominal magnetic resonance imaging (MRI), with larger adverse effects for olanzapine.
    Time Frame 12 weeks

    Outcome Measure Data

    Analysis Population Description
    Modified Intent to Treat (ITT) sample with week 0 and week 12 data.
    Arm/Group Title Risperidone Olanzapine Aripiprazole
    Arm/Group Description 12 weeks of randomized treatment with flexibly dosed risperidone 12 weeks of randomized treatment with flexibly dosed olanzapine 12 weeks of randomized treatment with flexibly dosed aripiprazole
    Measure Participants 30 26 30
    Mean (Standard Deviation) [Change in cm-squared]
    18.21
    (22.27)
    34.27
    (27.22)
    15.84
    (19.02)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Risperidone, Olanzapine, Aripiprazole
    Comments Repeated measures ANCOVA was used to test for the main effect of time on the outcome, and to test for a time by treatment condition interaction that would indicate differences between groups in change over time in the primary outcome. The null hypotheses were that there was no difference in the outcome over time (main effect of time) and that there were no differences between groups in the change over time (time by treatment condition).
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.003
    Comments
    Method ANCOVA
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Risperidone, Olanzapine
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments Bonferroni correction for multiple comparisons was applied (p<0.05/4 = 0.0125).
    Method Contrast
    Comments Contrasts based on the ANCOVA-derived time by treatment condition interaction.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Olanzapine, Aripiprazole
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments Bonferroni correction for multiple comparisons was applied (p<0.05/4 = 0.0125).
    Method ANCOVA
    Comments Contrasts based on the ANCOVA-derived time by treatment condition interaction.

    Adverse Events

    Time Frame Adverse events were collected throughout the entire course of the study, April 2006 to July 2011 or 6 years and 3 months
    Adverse Event Reporting Description
    Arm/Group Title Aripiprazole Olanzapine Risperidone
    Arm/Group Description Participants in this group were randomized to treatment with aripiprazole. Participants in this group were randomized to treatment with olanzapine. Participants in this group were randomized to treatment with risperidone.
    All Cause Mortality
    Aripiprazole Olanzapine Risperidone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/49 (0%) 0/46 (0%) 0/49 (0%)
    Serious Adverse Events
    Aripiprazole Olanzapine Risperidone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/49 (0%) 0/46 (0%) 1/49 (2%)
    Nervous system disorders
    Seizure 0/49 (0%) 0 0/46 (0%) 0 1/49 (2%) 1
    Other (Not Including Serious) Adverse Events
    Aripiprazole Olanzapine Risperidone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 38/49 (77.6%) 38/46 (82.6%) 39/49 (79.6%)
    Psychiatric disorders
    Accidental Injury 3/49 (6.1%) 3/46 (6.5%) 5/49 (10.2%)
    Agitation 15/49 (30.6%) 21/46 (45.7%) 16/49 (32.7%)
    Anxiety 9/49 (18.4%) 10/46 (21.7%) 13/49 (26.5%)
    Constipation 1/49 (2%) 2/46 (4.3%) 7/49 (14.3%)
    Depression 1/49 (2%) 5/46 (10.9%) 4/49 (8.2%)
    Difficulty Concentrating 10/49 (20.4%) 12/46 (26.1%) 16/49 (32.7%)
    Drowsiness/Somnolence 11/49 (22.4%) 10/46 (21.7%) 8/49 (16.3%)
    Headache 4/49 (8.2%) 4/46 (8.7%) 5/49 (10.2%)
    Increased Appetite 18/49 (36.7%) 31/46 (67.4%) 15/49 (30.6%)
    Involuntary Movements 0/49 (0%) 1/46 (2.2%) 4/49 (8.2%)
    Restlessness 12/49 (24.5%) 12/46 (26.1%) 14/49 (28.6%)
    Runny Nose 6/49 (12.2%) 1/46 (2.2%) 1/49 (2%)
    Sleepiness 5/49 (10.2%) 9/46 (19.6%) 4/49 (8.2%)
    Thirst 1/49 (2%) 3/46 (6.5%) 1/49 (2%)
    Tiredness/Fatigue 6/49 (12.2%) 6/46 (13%) 2/49 (4.1%)
    Trouble Sleeping 4/49 (8.2%) 3/46 (6.5%) 8/49 (16.3%)
    Weight Gain 11/49 (22.4%) 23/46 (50%) 20/49 (40.8%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title John W. Newcomer
    Organization Florida Atlantic University
    Phone (561) 297-0252
    Email jnewcomer@health.fau.edu
    Responsible Party:
    Washington University School of Medicine
    ClinicalTrials.gov Identifier:
    NCT00205699
    Other Study ID Numbers:
    • NIMH
    • R01MH072912
    First Posted:
    Sep 20, 2005
    Last Update Posted:
    Jun 15, 2018
    Last Verified:
    Jun 1, 2018