Healthy
Conditions
Keywords
Healthy volunteers, antipsychotic drugs, brain metabolism
Brief summary
The primary aim of this study is to investigate antipsychotic drug effects on healthy brain metabolism.
Detailed description
Schizophrenia is a complex psychiatric disorder characterized by alterations in brain structure. It is not clear yet whether some of these alterations are primarily related to pathophysiology of illness per se or consequence of brain exposure to the effects of psychotropic drugs. In recent years accumulating evidence suggests that exposure to the effects of psychotropic drugs may contribute to the structural and other changes in brain. Therefore, use of antipsychotic medications as treatment for schizophrenia represents a potential confounding factor in many of the studies. Most neuroimaging studies of schizophrenia to date have not included the examination of non-medicated patients, making conclusions about medication effects on neuroimaging measures difficult. MRI studies of structural brain changes across time are limited by the fact that due to ethical reasons neither untreated subjects with schizophrenia nor control subjects exposed to antipsychotic medications can be used as comparison groups. There are some preclinical rat and primate models which revealed chronic antipsychotic-induced alterations in the brain. However few studies investigate the effects of chronic exposure to antipsychotic drugs on healthy human brain. Therefore in this study, investigators aimed to evaluate brain alterations induced by chronic drug exposure in healthy volunteers. To address this problem, we will conduct a single-site, single arm, open-label, interventional, multimodal neuroimaging study of healthy comparison subjects who are exposed to antipsychotic medication for 15 days. This study will include up to 40 healthy adult (21-50 years old) volunteers. Participants will be recruited via online advertisements and flyers as well as approaching healthy individuals who participated in previous studies. Investigators have three aims: 1. to study the levels of chemicals and kinetics of enzymes associated with cellular energy metabolism in brain before and after use of antipsychotic drug (using 1P MRS). 2. to collect data on the structure of the gray matter and white matter; resting state functional brain activity; levels of brain chemicals including glutamate and GABA; and white matter integrity before and after use of antipsychotic drug (using structural MRI, fMRI, dTI, 1H MRS). 3. to investigate side effects of antipsychotic drugs. It was planed to give healthy participants a single 2.5 mg dose of olanzapine followed by a 5 mg dose for 14 days. Olanzapine, a second generation antipsychotic agent, was selected to administer because this medication has strong effects on energy metabolism in general. The recommended daily dose range for olanzapine is indicated as 10-30 mg/d in the last APA (American Psychiatric Association) Practice Guideline for the Treatment of Patients With Schizophrenia. A recent study suggests that minimum effective dose for olanzapine in schizophrenia is 7.5 mg/d (the upper range of 5 mg ± 2.5 mg/d) and higher olanzapine doses (10, 10 ± 2.5, 15, and 15 ± 2.5 mg/d) are more efficacious than placebo. Therefore it was determined to give healthy subjects only 5 mg/d olanzapine, the lower limit of the optimal dose range (5 mg ± 2.5 mg/d), to mimic the therapeutic effect but also protect the participants from adverse effects of treatment. As the goal is to examine the effects of chronic drug use, the duration of medication was determined to be 15 days, the longest but historically safe olanzapine usage period in healthy individuals up to now. There is no published literature on the effects of olanzapine on brain measures. Therefore, it is not possible to calculate a sample size that would detect a given between-group difference in this study. Investigators plan to recruit a sample that is large enough to establish the absence of a moderate or large effect. It was proposed that sample size of 30 subjects will be sufficient to detect a difference with effect sizes of 0.45 or greater as significant at the p\<0.05 level with 80% power. Effect sizes of 0.5 are generally considered moderate and 0.8 considered large. Therefore, a not-statistically significant finding with this sample size will suggest that any effects of olanzapine on brain metabolism are small at most. Investigators will collect interview and neuroimaging data at baseline and after the medication period. Deviations induced by the study drug on healthy brain will be examined using paired t-tests for before and after measurements. Investigation of parameters before and after the use of antipsychotic drug in healthy people will give a chance to determine brain alterations related to drug itself, independent from the pathophysiology of the illness.
Interventions
DRUGOlanzapine
All subjects will take a single 2.5 mg dose of olanzapine (Zyprexa Zydis) followed by a 5 mg dose for 14 days. (2.5 mg/d for 1 day, 5 mg/d for 14 days).
Sponsors
Dost Ongur
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Age: 21-50 years old * Male or female * Without psychiatric diagnosis according to a structured psychiatric interview (SCID) * Without history of a psychotic disorder among parents, siblings, or children
Exclusion criteria
* Significant medical or neurological illness * Diagnosis diabetes mellitus, uncontrolled hypertension, severe hypotension, coronary artery disease, metabolic syndrome, glaucoma, liver impairment, decreased renal function, respiratory disorders, peptic ulcer disease (absolute and relative contraindications to use of antipsychotic drugs) * Body mass index (BMI) over 30 * Taking any other medications, including over the counter supplements with the exception of oral contraceptives for women * Pregnancy. Females of child-bearing age must be using an effective contraceptive method * History of smoking, substance abuse or dependence * Contraindication to MR scan (claustrophobia, cardiac pacemakers, metal clips and stents on blood vessels, artificial heart valves, artificial arms, hands, legs, etc., brain stimulator devices, implanted drug pumps, ear implants, eye implants or known metal fragments in eyes, exposure to shrapnel or metal filings, other metallic surgical hardware in vital areas, certain tattoos with metallic ink, certain transdermal patches, metal-containing IUDs) * Medical condition that would prevent blood draws
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Brain Phosphocreatine (PCr) | Baseline and after 15 days medication period | Change in Phosphocreatine (PCr) metabolite concentration as measured by in vivo 31P magnetic resonance spectroscopy |
| Change in Brain Nicotinamide Adenine Dinucleotide Metabolites NAD+/NADH | Baseline and after 15 days medication period | Change in brain nicotinamide adenine dinucleotide NAD+/NADH metabolite ratio as measured by in vivo 31P magnetic resonance spectroscopy |
| Change in Brain Creatine Kinase (CK) Forward Reaction Rate | Baseline and after 15 days medication period | Change in forward reaction rate constant (kf) of the creatine kinase (CK) as measured by in vivo 31P magnetic resonance spectroscopy magnetization transfer |
| Change in Brain Parenchymal pH | baseline and after 15 days medication period | Change in brain parenchymal pH as measured by in vivo 31P magnetic resonance spectroscopy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fractional Anisotropy (FA) Measured by Diffusion Tensor Imaging (DTI) | baseline and after 15 days medication period | Change in fractional anisotropy (FA), a scalar measure of diffusivity, of water in the brain assessed by DTI at 3T. FA values range from 0 (isotropic, meaning diffusion is equally restricted in 3D space) to 1 (anisotrophic, meaning that diffusion is completely restricted to a single direction). |
| Change in Volumes of the Frontal, Parietal and Temporal Lobe Regions | baseline and after 15 day medication period | Change in the gray matter volumes (cubic millimeters) of the frontal, parietal and temporal lobes as defined by Freesurfer's Desikan-Killiany Brain Atlas. Data was acquired using structural magnetic resonance imaging (MRI) at 3T. |
| Change in MATRICS Cognitive Consensus Battery (MCCB) Total Composite Score | baseline and after 15 days medication period | Change in the MATRICS Cognitive Consensus Battery (MCCB), that includes 10 tasks that measure processing speed (Brief Assessment of Cognition in Schizophrenia - Symbol Coding, Animal Fluency, Trails A), attention (Continuous Performance Test), working memory (WMS-III Spatial Span, Letter-Number Span), verbal learning (Hopkins Verbal Learning Test - Revised), visual learning (Brief Visuospatial Memory Test - Revised), problem solving (Neuropsychological Assessment Battery Mazes) and social cognition (Mayer-Salovey-Caruso Emotional Intelligence Test). Scores from each subtest are normed and their T-scores are summed to yield a MCCB composite score, then the total composite T-score is standardized to normative data among a healthy population. The composite T-score has a mean of 50 and a standard deviation of 10. Higher total composite scores indicate better cognitive outcomes. |
| Change in Glutamate Metabolite Concentration | baseline and after 15 days medication period | Change in glutamate metabolite concentration measured by proton magnetic resonance spectroscopy. |
| Change in Surface Area of the Frontal, Parietal and Temporal Regions | baseline and after 15 days medication period | Change in the cortical surface area (millimeters squared) of the frontal, parietal and temporal lobes as defined by Freesurfer's Desikan-Killiany Brain Atlas. Data was acquired using structural magnetic resonance imaging (MRI) at 3T. |
| Change in fMRI Resting State Functional Connectivity | baseline and after 15 days medication period | Change in resting state functional connectivity to the medial prefrontal cortex and superior parietal lobules following olanzapine administration period. Whole-brain, seed-to-voxel analyses were conducted utilizing anatomically-defined seed regions and age-corrected within-subjects f-tests were run to determine the presence and size (in voxels) of clusters where connectivity changed significantly following olanzapine administration. Results are reported in units of voxels for each cluster meeting a threshold of voxel-level uncorrected p\<.001 and cluster-level p-FDR\<.05. A result of zero indicates that no clusters were identified within subjects as changed in connectivity relative to the seed regions. |
| Change in GABA Concentration | baseline and after 15 days medication period | Change in GABA concentration measured by proton magnetic resonance spectroscopy. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Fasting Total Cholesterol Level | baseline and after 15 days medication period | Change in fasting total cholesterol level |
| Change in Hemoglobin A1c Level | baseline and after 15 days medication period | Change in fasting, Hemoglobin A1c level |
| Change in Serum Insulin Levels | baseline and after 15 days medication period | Change in insulin fasting serum levels |
| Change in Prolactin Levels | baseline and after 15 days medication period | Change prolactin serum levels |
| Change in Total Caloric Intake | baseline and after 15 days medication period | Change in total caloric intake as assessed by the ASA24 Dietary Recall and Food Frequency Questionnaire - Revised. The ASA24 is a self-administered 24-hour dietary recall assessment. |
| Change in Montgomery-Asberg Depression Rating Scale (MADRS) Score | baseline and after 15 days medication period | Change in Montgomery-Asberg Depression Rating Scale (MADRS) score, a 0-60 point scale rating depressive symptoms. Higher scores indicate more severe clinical symptoms. |
| Change in the Early Psychosis Social Scale Survey Score | baseline and after 15 days medication period | Change in the Early Psychosis Social Scale score item of missed absences from school or work. Scores range from 1-5, with higher scores indicating more absences from school or work. |
| Change in the Prodromal Questionnaire, Brief Version Total Score | baseline and after 15 days medication period | Change in the Prodromal Questionnaire, Brief Version score, a 21 item self-report questionnaire designed to help identify those at ultra-high risk for developing psychotic symptoms. The total score is derived as the sum of all 21 items, with a possible range of 0-21. Higher scores indicate greater psychopathology. |
| Change in the Symptoms Checklist - 90 - Revised Global Severity Score | baseline and after 15 days medication period | Changes in the Symptoms Checklist - 90 - Revised scale, which measures 9 domains of psychological dysfunction, summing to create an overall psychological distress (Global Severity Score). The scores of each of the 9 domains - somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation and psychoticism - combine for a total of 90 items, each measured on a 5-point scale. The sums of all 90 item scores, ranging 0-360, creates the Global Severity score. Higher scores indicate greater psychopathology. |
| Change in the State-Trait Anxiety Inventory for Adults Scores | baseline and after 15 days medication period | Change in the State-Trait Anxiety Inventory for Adults, which measures both state and trait anxiety using 2 subscales for a total of 40 items. Each subscale has a range of 20-80, with higher scores indicating greater state or trait anxiety, respectively. |
| Change in the World Health Organization Quality of Life Questionnaire Score | baseline and after 15 days medication period | Change in the World Health Organization Quality of Life questionnaire score, a 26-item assessment of overall quality of life. The questionnaire encompasses 4 domains: physical health, psychological health, social relationships, and environment. There are two additional questions, which assess the participant's perceptions of their own quality of life and physical health. Higher scores indicate better quality of life. Scores are summed within each domain. Total score is obtained by transforming for a total range of 0-100 within each domain. |
| Change in The Wisconsin Schizotypy Scales - Short Form Scores | baseline and after 15 days medication period | Change in Wisconsin Schizotypy Scales (WSS) Short Form score, a self-report questionnaire assessing schizotypy in clinical and non-clinical samples. The measure has four scales, each with 15 True/False questions. There are 13 red-herring questions, that, if answered True invalidate the test. Each false response is scored 0, and each true response is scored 1. Scores for each scale range from 0 - 15, with higher scores indicating greater schizotypy. The WSS positive schizotypy score consists of the summed score of the perceptual aberration and magical ideation scales and scores range from 0-30, with higher scores indicating greater positive schizotypy. The WSS negative schizotypy score sums scores from the physical anhedonia and social anhedonia scales and ranges from 0-30, with higher scores indicating greater negative schizotypy. |
| Change in Beck Depression Inventory (BDI) Score | baseline and after 15 days medication period | Change in Beck Depression Inventory (BDI) score, a self-report questionnaire measuring depressive symptoms on a scale of 0-63. Scores ranging 0-9 generally indicate minimal depressive symptoms, while scores 10-18 indicate mild, 19-29 indicates moderate, and 30-63 indicates severe depressive symptoms, respectively. |
| Change in Young Mania Rating Scale (YMRS) Score | baseline and after 15 days medication period | Change in Young Mania Rating Scale (YMRS) score, an interview-based, 11-item scale that measures the severity of core features of clinical mania. 7 items are scored on a 0-4 point scale, while the remaining 4 are scored on a 0-8 point scale, for a total possible range of 0-64. Higher scores indicate more severe manic symptoms. |
| Change in Beck Anxiety Inventory (BAI) Score | baseline and after 15 days medication period | Change in Beck Anxiety Inventory (BAI) score, a self-report measure of anxiety symptoms. Scores range from 0-63, with higher scores indicating more severe anxiety. |
| Change in The Columbia Suicide Severity Rating Scale Score | baseline and 2, 5, 10, 15 days during medication period | Change in The Columbia Suicide Severity Rating Scale score, a self-report scale measuring suicidality. Only the total score, not subscale of suicidal ideation intensity, will be measured. Total scores can range from 0-10, with higher scores indicating increased suicidality. |
| Change in Pittsburgh Sleep Quality Index Score | baseline and after 15 days medication period | Change in Pittsburgh Sleep Quality Index score, a measurement of sleep quality. The index measures 7 sleep components on a 0-3 scale; each of the 7 raw scores is summed to get a global score. The global score ranges from 0-21, with higher scores indicating poor sleep quality. Scores \>5 are typically considered poor sleep quality. |
| Change in LUNSERS (Liverpool University Neuroleptic Side Effect Rating Scale) Score | baseline and 2, 5, 10 and 15 days (or final assessment) during medication period | Change in LUNSERS (Liverpool University Neuroleptic Side Effect Rating Scale) score, a self-report measure of antipsychotic side effects. The scale has 51 questions, 41 of which are about side-effects and 10 red herrings for validation purposes. The total neuroleptic side effect score is derived from the sum of the 41 side-effect questions, with a potential range of 0-164. Higher scores indicate more severe neuroleptic side effects. |
| Change in Body Weight | baseline and 2, 5, 10 and 15 days (or final assessment) during medication period | Change in participant body weight in kg, as measured using a standing scale. |
| Change in Hip Circumference | baseline and 2, 5, 10 and 15 days (or final assessment) during medication period | Change in the hip circumference measurement, taken as an average of 3 measures by tape measure |
| Change in Waist Circumference | baseline and 2, 5, 10 and 15 days (or final assessment) during medication period | Change in waist circumference measurements, taken as an average of 3 measures by tape measure. |
| Change in Blood Glucose Levels | baseline and after 15 days during medication period | Change in fasting serum glucose levels. |
Countries
United States
Participant flow
Recruitment details
Individuals between 21-50 years old without a psychiatric or serious medical diagnosis or family history or first degree relative with a psychotic disorder.
Participants by arm
| Arm | Count |
|---|---|
| Second Generation Antipsychotic Drug Olanzapine; a single 2.5 mg dose PO daily followed by 5 mg dose PO daily for 14 days
Olanzapine: All subjects will take a single 2.5 mg dose of olanzapine (Zyprexa Zydis) followed by a 5 mg dose for 14 days. (2.5 mg/d for 1 day, 5 mg/d for 14 days). | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Second Generation Antipsychotic Drug |
|---|---|
| Age, Continuous | 25.42 years STANDARD_DEVIATION 2.23 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Change in Brain Creatine Kinase (CK) Forward Reaction Rate
Change in forward reaction rate constant (kf) of the creatine kinase (CK) as measured by in vivo 31P magnetic resonance spectroscopy magnetization transfer
Time frame: Baseline and after 15 days medication period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine | Change in Brain Creatine Kinase (CK) Forward Reaction Rate | -0.04 s-1 | Standard Deviation 0.08 |
Primary
Change in Brain Nicotinamide Adenine Dinucleotide Metabolites NAD+/NADH
Change in brain nicotinamide adenine dinucleotide NAD+/NADH metabolite ratio as measured by in vivo 31P magnetic resonance spectroscopy
Time frame: Baseline and after 15 days medication period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine | Change in Brain Nicotinamide Adenine Dinucleotide Metabolites NAD+/NADH | -0.79 ratio | Standard Deviation 2.37 |
Primary
Change in Brain Parenchymal pH
Change in brain parenchymal pH as measured by in vivo 31P magnetic resonance spectroscopy
Time frame: baseline and after 15 days medication period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine | Change in Brain Parenchymal pH | 0.00 pH | Standard Deviation 0.01 |
Primary
Change in Brain Phosphocreatine (PCr)
Change in Phosphocreatine (PCr) metabolite concentration as measured by in vivo 31P magnetic resonance spectroscopy
Time frame: Baseline and after 15 days medication period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine | Change in Brain Phosphocreatine (PCr) | 0.01 ratio | Standard Deviation 0.11 |
Secondary
Change in fMRI Resting State Functional Connectivity
Change in resting state functional connectivity to the medial prefrontal cortex and superior parietal lobules following olanzapine administration period. Whole-brain, seed-to-voxel analyses were conducted utilizing anatomically-defined seed regions and age-corrected within-subjects f-tests were run to determine the presence and size (in voxels) of clusters where connectivity changed significantly following olanzapine administration. Results are reported in units of voxels for each cluster meeting a threshold of voxel-level uncorrected p\<.001 and cluster-level p-FDR\<.05. A result of zero indicates that no clusters were identified within subjects as changed in connectivity relative to the seed regions.
Time frame: baseline and after 15 days medication period
Population: Number of voxels that showed significant change in connectivity following administration of olanzapine.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Olanzapine | Change in fMRI Resting State Functional Connectivity | medial prefrontal cortex | 0 Voxels |
| Olanzapine | Change in fMRI Resting State Functional Connectivity | superior parietal lobule | 0 Voxels |
Secondary
Change in Fractional Anisotropy (FA) Measured by Diffusion Tensor Imaging (DTI)
Change in fractional anisotropy (FA), a scalar measure of diffusivity, of water in the brain assessed by DTI at 3T. FA values range from 0 (isotropic, meaning diffusion is equally restricted in 3D space) to 1 (anisotrophic, meaning that diffusion is completely restricted to a single direction).
Time frame: baseline and after 15 days medication period
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change in Fractional Anisotropy (FA) Measured by Diffusion Tensor Imaging (DTI) | Core FA | 0.0007 Units on a scale | Standard Deviation 0.01 |
| Olanzapine | Change in Fractional Anisotropy (FA) Measured by Diffusion Tensor Imaging (DTI) | Genu of corpus callosum | -0.003 Units on a scale | Standard Deviation 0.013 |
| Olanzapine | Change in Fractional Anisotropy (FA) Measured by Diffusion Tensor Imaging (DTI) | Cingulum | -0.008 Units on a scale | Standard Deviation 0.027 |
| Olanzapine | Change in Fractional Anisotropy (FA) Measured by Diffusion Tensor Imaging (DTI) | Inferior fronto-occipital fasciculus | -0.002 Units on a scale | Standard Deviation 0.012 |
| Olanzapine | Change in Fractional Anisotropy (FA) Measured by Diffusion Tensor Imaging (DTI) | Anterior thalamic radiation | 0.002 Units on a scale | Standard Deviation 0.015 |
Secondary
Change in GABA Concentration
Change in GABA concentration measured by proton magnetic resonance spectroscopy.
Time frame: baseline and after 15 days medication period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine | Change in GABA Concentration | 0.11 mmol | Standard Deviation 0.2 |
Secondary
Change in Glutamate Metabolite Concentration
Change in glutamate metabolite concentration measured by proton magnetic resonance spectroscopy.
Time frame: baseline and after 15 days medication period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine | Change in Glutamate Metabolite Concentration | 0.13 millimoles | Standard Deviation 0.66 |
Secondary
Change in MATRICS Cognitive Consensus Battery (MCCB) Total Composite Score
Change in the MATRICS Cognitive Consensus Battery (MCCB), that includes 10 tasks that measure processing speed (Brief Assessment of Cognition in Schizophrenia - Symbol Coding, Animal Fluency, Trails A), attention (Continuous Performance Test), working memory (WMS-III Spatial Span, Letter-Number Span), verbal learning (Hopkins Verbal Learning Test - Revised), visual learning (Brief Visuospatial Memory Test - Revised), problem solving (Neuropsychological Assessment Battery Mazes) and social cognition (Mayer-Salovey-Caruso Emotional Intelligence Test). Scores from each subtest are normed and their T-scores are summed to yield a MCCB composite score, then the total composite T-score is standardized to normative data among a healthy population. The composite T-score has a mean of 50 and a standard deviation of 10. Higher total composite scores indicate better cognitive outcomes.
Time frame: baseline and after 15 days medication period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine | Change in MATRICS Cognitive Consensus Battery (MCCB) Total Composite Score | 3.63 Score on a scale | Standard Deviation 4.72 |
Secondary
Change in Surface Area of the Frontal, Parietal and Temporal Regions
Change in the cortical surface area (millimeters squared) of the frontal, parietal and temporal lobes as defined by Freesurfer's Desikan-Killiany Brain Atlas. Data was acquired using structural magnetic resonance imaging (MRI) at 3T.
Time frame: baseline and after 15 days medication period
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change in Surface Area of the Frontal, Parietal and Temporal Regions | Frontal lobe | -801.19 mm^2 | Standard Deviation 1563.02 |
| Olanzapine | Change in Surface Area of the Frontal, Parietal and Temporal Regions | Parietal lobe | -581.56 mm^2 | Standard Deviation 1272.93 |
Secondary
Change in Volumes of the Frontal, Parietal and Temporal Lobe Regions
Change in the gray matter volumes (cubic millimeters) of the frontal, parietal and temporal lobes as defined by Freesurfer's Desikan-Killiany Brain Atlas. Data was acquired using structural magnetic resonance imaging (MRI) at 3T.
Time frame: baseline and after 15 day medication period
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change in Volumes of the Frontal, Parietal and Temporal Lobe Regions | Frontal Lobe | -2500.44 cubic mm | Standard Deviation 4304.17 |
| Olanzapine | Change in Volumes of the Frontal, Parietal and Temporal Lobe Regions | Parietal Lobe | -600 cubic mm | Standard Deviation 1264.79 |
Other Pre-specified
Change in Beck Anxiety Inventory (BAI) Score
Change in Beck Anxiety Inventory (BAI) score, a self-report measure of anxiety symptoms. Scores range from 0-63, with higher scores indicating more severe anxiety.
Time frame: baseline and after 15 days medication period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine | Change in Beck Anxiety Inventory (BAI) Score | -0.63 score on a scale | Standard Deviation 1.41 |
Other Pre-specified
Change in Beck Depression Inventory (BDI) Score
Change in Beck Depression Inventory (BDI) score, a self-report questionnaire measuring depressive symptoms on a scale of 0-63. Scores ranging 0-9 generally indicate minimal depressive symptoms, while scores 10-18 indicate mild, 19-29 indicates moderate, and 30-63 indicates severe depressive symptoms, respectively.
Time frame: baseline and after 15 days medication period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine | Change in Beck Depression Inventory (BDI) Score | -0.63 score on a scale | Standard Deviation 1.3 |
Other Pre-specified
Change in Blood Glucose Levels
Change in fasting serum glucose levels.
Time frame: baseline and after 15 days during medication period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine | Change in Blood Glucose Levels | 0.75 mg/dL | Standard Deviation 6.18 |
Other Pre-specified
Change in Body Weight
Change in participant body weight in kg, as measured using a standing scale.
Time frame: baseline and 2, 5, 10 and 15 days (or final assessment) during medication period
Population: Data for this measure was collected for 10 participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change in Body Weight | Baseline | 0 kg | Standard Deviation 0 |
| Olanzapine | Change in Body Weight | 2 days | -0.29 kg | Standard Deviation 1.13 |
| Olanzapine | Change in Body Weight | 5 days | 0.12 kg | Standard Deviation 1.41 |
| Olanzapine | Change in Body Weight | 10 days | 0.21 kg | Standard Deviation 0.88 |
| Olanzapine | Change in Body Weight | Endpoint | 0.73 kg | Standard Deviation 1.34 |
Other Pre-specified
Change in Fasting Total Cholesterol Level
Change in fasting total cholesterol level
Time frame: baseline and after 15 days medication period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine | Change in Fasting Total Cholesterol Level | -1.75 mg/dL | Standard Deviation 28.23 |
Other Pre-specified
Change in Hemoglobin A1c Level
Change in fasting, Hemoglobin A1c level
Time frame: baseline and after 15 days medication period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine | Change in Hemoglobin A1c Level | -0.01 mmol/mol | Standard Deviation 0.11 |
Other Pre-specified
Change in Hip Circumference
Change in the hip circumference measurement, taken as an average of 3 measures by tape measure
Time frame: baseline and 2, 5, 10 and 15 days (or final assessment) during medication period
Population: Data for this measure was collected for 10 participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change in Hip Circumference | Baseline | 0 cm | Standard Deviation 0 |
| Olanzapine | Change in Hip Circumference | 2 days | -0.43 cm | Standard Deviation 3.1 |
| Olanzapine | Change in Hip Circumference | 5 days | -1.10 cm | Standard Deviation 4.27 |
| Olanzapine | Change in Hip Circumference | 10 days | -1.62 cm | Standard Deviation 4.89 |
| Olanzapine | Change in Hip Circumference | Endpoint | -1.24 cm | Standard Deviation 3.54 |
Other Pre-specified
Change in LUNSERS (Liverpool University Neuroleptic Side Effect Rating Scale) Score
Change in LUNSERS (Liverpool University Neuroleptic Side Effect Rating Scale) score, a self-report measure of antipsychotic side effects. The scale has 51 questions, 41 of which are about side-effects and 10 red herrings for validation purposes. The total neuroleptic side effect score is derived from the sum of the 41 side-effect questions, with a potential range of 0-164. Higher scores indicate more severe neuroleptic side effects.
Time frame: baseline and 2, 5, 10 and 15 days (or final assessment) during medication period
Population: Data for this measure was collected for 10 participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change in LUNSERS (Liverpool University Neuroleptic Side Effect Rating Scale) Score | 2 days | 4.50 score on a scale | Standard Deviation 4.99 |
| Olanzapine | Change in LUNSERS (Liverpool University Neuroleptic Side Effect Rating Scale) Score | 5 days | 2.11 score on a scale | Standard Deviation 3.02 |
| Olanzapine | Change in LUNSERS (Liverpool University Neuroleptic Side Effect Rating Scale) Score | Baseline | 0.20 score on a scale | Standard Deviation 0.63 |
| Olanzapine | Change in LUNSERS (Liverpool University Neuroleptic Side Effect Rating Scale) Score | 10 days | 2.22 score on a scale | Standard Deviation 3.19 |
| Olanzapine | Change in LUNSERS (Liverpool University Neuroleptic Side Effect Rating Scale) Score | Endpoint | 3.90 score on a scale | Standard Deviation 4.98 |
Other Pre-specified
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Score
Change in Montgomery-Asberg Depression Rating Scale (MADRS) score, a 0-60 point scale rating depressive symptoms. Higher scores indicate more severe clinical symptoms.
Time frame: baseline and after 15 days medication period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine | Change in Montgomery-Asberg Depression Rating Scale (MADRS) Score | -0.88 score on a scale | Standard Deviation 3 |
Other Pre-specified
Change in Pittsburgh Sleep Quality Index Score
Change in Pittsburgh Sleep Quality Index score, a measurement of sleep quality. The index measures 7 sleep components on a 0-3 scale; each of the 7 raw scores is summed to get a global score. The global score ranges from 0-21, with higher scores indicating poor sleep quality. Scores \>5 are typically considered poor sleep quality.
Time frame: baseline and after 15 days medication period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine | Change in Pittsburgh Sleep Quality Index Score | -0.63 score on a scale | Standard Deviation 1.92 |
Other Pre-specified
Change in Prolactin Levels
Change prolactin serum levels
Time frame: baseline and after 15 days medication period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine | Change in Prolactin Levels | 11.77 ng/mL | Standard Deviation 20.69 |
Other Pre-specified
Change in Serum Insulin Levels
Change in insulin fasting serum levels
Time frame: baseline and after 15 days medication period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine | Change in Serum Insulin Levels | -0.94 uIU/mL | Standard Deviation 1.73 |
Other Pre-specified
Change in The Columbia Suicide Severity Rating Scale Score
Change in The Columbia Suicide Severity Rating Scale score, a self-report scale measuring suicidality. Only the total score, not subscale of suicidal ideation intensity, will be measured. Total scores can range from 0-10, with higher scores indicating increased suicidality.
Time frame: baseline and 2, 5, 10, 15 days during medication period
Population: Data for this measure was collected for 10 participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change in The Columbia Suicide Severity Rating Scale Score | Baseline | 0 score on a scale | Standard Deviation 0 |
| Olanzapine | Change in The Columbia Suicide Severity Rating Scale Score | After 2 days medication | 0 score on a scale | Standard Deviation 0 |
| Olanzapine | Change in The Columbia Suicide Severity Rating Scale Score | After 5 days medication | 0 score on a scale | Standard Deviation 0 |
| Olanzapine | Change in The Columbia Suicide Severity Rating Scale Score | After 10 days medication | 0 score on a scale | Standard Deviation 0 |
| Olanzapine | Change in The Columbia Suicide Severity Rating Scale Score | After 15 days medication | 0 score on a scale | Standard Deviation 0 |
Other Pre-specified
Change in the Early Psychosis Social Scale Survey Score
Change in the Early Psychosis Social Scale score item of missed absences from school or work. Scores range from 1-5, with higher scores indicating more absences from school or work.
Time frame: baseline and after 15 days medication period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine | Change in the Early Psychosis Social Scale Survey Score | -0.13 score on a scale | Standard Deviation 0.35 |
Other Pre-specified
Change in the Prodromal Questionnaire, Brief Version Total Score
Change in the Prodromal Questionnaire, Brief Version score, a 21 item self-report questionnaire designed to help identify those at ultra-high risk for developing psychotic symptoms. The total score is derived as the sum of all 21 items, with a possible range of 0-21. Higher scores indicate greater psychopathology.
Time frame: baseline and after 15 days medication period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine | Change in the Prodromal Questionnaire, Brief Version Total Score | 0 score on a scale | Standard Deviation 0 |
Other Pre-specified
Change in the State-Trait Anxiety Inventory for Adults Scores
Change in the State-Trait Anxiety Inventory for Adults, which measures both state and trait anxiety using 2 subscales for a total of 40 items. Each subscale has a range of 20-80, with higher scores indicating greater state or trait anxiety, respectively.
Time frame: baseline and after 15 days medication period
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change in the State-Trait Anxiety Inventory for Adults Scores | Change in State-anxiety scale | -0.25 score on a scale | Standard Deviation 2.38 |
| Olanzapine | Change in the State-Trait Anxiety Inventory for Adults Scores | Change in Trait-anxiety scale | -0.75 score on a scale | Standard Deviation 2.38 |
Other Pre-specified
Change in the Symptoms Checklist - 90 - Revised Global Severity Score
Changes in the Symptoms Checklist - 90 - Revised scale, which measures 9 domains of psychological dysfunction, summing to create an overall psychological distress (Global Severity Score). The scores of each of the 9 domains - somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation and psychoticism - combine for a total of 90 items, each measured on a 5-point scale. The sums of all 90 item scores, ranging 0-360, creates the Global Severity score. Higher scores indicate greater psychopathology.
Time frame: baseline and after 15 days medication period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine | Change in the Symptoms Checklist - 90 - Revised Global Severity Score | -2.33 score on a scale | Standard Deviation 5.66 |
Other Pre-specified
Change in The Wisconsin Schizotypy Scales - Short Form Scores
Change in Wisconsin Schizotypy Scales (WSS) Short Form score, a self-report questionnaire assessing schizotypy in clinical and non-clinical samples. The measure has four scales, each with 15 True/False questions. There are 13 red-herring questions, that, if answered True invalidate the test. Each false response is scored 0, and each true response is scored 1. Scores for each scale range from 0 - 15, with higher scores indicating greater schizotypy. The WSS positive schizotypy score consists of the summed score of the perceptual aberration and magical ideation scales and scores range from 0-30, with higher scores indicating greater positive schizotypy. The WSS negative schizotypy score sums scores from the physical anhedonia and social anhedonia scales and ranges from 0-30, with higher scores indicating greater negative schizotypy.
Time frame: baseline and after 15 days medication period
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change in The Wisconsin Schizotypy Scales - Short Form Scores | Change in positive schizotypy subscales | 0.06 score on a scale | Standard Deviation 0.12 |
| Olanzapine | Change in The Wisconsin Schizotypy Scales - Short Form Scores | Change in negative schizotypy subscales | 0.09 score on a scale | Standard Deviation 0.42 |
Other Pre-specified
Change in the World Health Organization Quality of Life Questionnaire Score
Change in the World Health Organization Quality of Life questionnaire score, a 26-item assessment of overall quality of life. The questionnaire encompasses 4 domains: physical health, psychological health, social relationships, and environment. There are two additional questions, which assess the participant's perceptions of their own quality of life and physical health. Higher scores indicate better quality of life. Scores are summed within each domain. Total score is obtained by transforming for a total range of 0-100 within each domain.
Time frame: baseline and after 15 days medication period
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change in the World Health Organization Quality of Life Questionnaire Score | Change in physical health score | 2.25 score on a scale | Standard Deviation 7.61 |
| Olanzapine | Change in the World Health Organization Quality of Life Questionnaire Score | Change in psychological health score | -4.38 score on a scale | Standard Deviation 7.25 |
| Olanzapine | Change in the World Health Organization Quality of Life Questionnaire Score | Change in social relationships score | 0.75 score on a scale | Standard Deviation 3.85 |
| Olanzapine | Change in the World Health Organization Quality of Life Questionnaire Score | Change in environment score | -7.875 score on a scale | Standard Deviation 12.15 |
Other Pre-specified
Change in Total Caloric Intake
Change in total caloric intake as assessed by the ASA24 Dietary Recall and Food Frequency Questionnaire - Revised. The ASA24 is a self-administered 24-hour dietary recall assessment.
Time frame: baseline and after 15 days medication period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine | Change in Total Caloric Intake | 151.94 kcal | Standard Deviation 1180.23 |
Other Pre-specified
Change in Waist Circumference
Change in waist circumference measurements, taken as an average of 3 measures by tape measure.
Time frame: baseline and 2, 5, 10 and 15 days (or final assessment) during medication period
Population: Data was collected for 10 participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change in Waist Circumference | Baseline | 0 cm | Standard Deviation 0 |
| Olanzapine | Change in Waist Circumference | After 2 days medication | -0.47 cm | Standard Deviation 3.21 |
| Olanzapine | Change in Waist Circumference | After 5 days medication | 0.22 cm | Standard Deviation 1.36 |
| Olanzapine | Change in Waist Circumference | After 10 days medication | -0.23 cm | Standard Deviation 3.3 |
| Olanzapine | Change in Waist Circumference | Endpoint | -0.15 cm | Standard Deviation 3.06 |
Other Pre-specified
Change in Young Mania Rating Scale (YMRS) Score
Change in Young Mania Rating Scale (YMRS) score, an interview-based, 11-item scale that measures the severity of core features of clinical mania. 7 items are scored on a 0-4 point scale, while the remaining 4 are scored on a 0-8 point scale, for a total possible range of 0-64. Higher scores indicate more severe manic symptoms.
Time frame: baseline and after 15 days medication period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine | Change in Young Mania Rating Scale (YMRS) Score | -0.875 score on a scale | Standard Deviation 1.126 |