Validation of Multidimensional Assessment of THYmic States (MATHYS): A Study in a Population of Bipolar Patients Treated With Olanzapine

Study Overview
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Brief Summary
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A non randomized study to validate the MATHYS Scale in a population of in and outpatients greater than or equal to 18 years of age, suffering from Bipolar Disorder I or II, and treated with olanzapine.

Official Title
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Phase IIIb, Multicenter, Single-Arm Open-Label Study, Supporting the Development and the Validation of the MATHYS Scale (Multidimensional Assessment of THYmic States) in a Population of Bipolar Patients Treated With Olanzapine, Either in-Label (Manic and Mixed Patients) and Off-Label (Hypomanic and Bipolar Depression)

Conditions
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Bipolar Disorder I or II

Intervention / Treatment
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* Drug: olanzapine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) disease diagnostic criteria for Bipolar Disorder currently or most recently in a Manic Episode (Single Manic Episode or Most Recent Episode Manic) or currently or most recently in a Hypomanic Episode or currently or most recently in a Mixed Episode or currently or most recently in a Major Depressive Episode and confirmed by the module D of the SCID (Semi-Structured Interview). Patients must be more than 18 of age at Visit 0. Exclusion Criteria: A valid current or lifetime DSM-IV-TR Axis I or II diagnosis which could interfere, at the investigator's opinion, with the evaluation. Patients on antidepressant or mood stabilizer therapy one week (four weeks with fluoxetine) prior to Visit 1, with the exception of mood stabilizer therapy considered in the opinion of the investigator as an efficient treatment for at least one year prior to the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: olanzapine<br>* 5 to 20 mg (flexible dose) administered orally as disintegrated tablets, daily for 24 weeks.<br>* Other names: Zydis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Changes From Baseline to 6 Week and 24 Week Endpoints in the Multidimensional Assessment of THYmic States Scale (MATHYS) Total Score | A visual analogic scale consisting of 20 items. Item scores vary from 0 (inhibition of the state evaluated by the item) to 10 (excitation for the evaluated state), except for items 5 to 10 and 17 and 18 which are inversed and are consequently to be reversed before the analysis. Total score is sum of the 20 items and can vary from 0 to 200. | Baseline, 6 Weeks, 24 weeks | 
| Baseline MATHYS Assessment - Principal Component Analysis and Orthogonal Transformation Matrix | This analysis indicates whether the total score is correct and provides enough information, or if subscores need to be calculated. Eigen value, proportion and cumulative are statistical parameters from the Principal Component Analysis, given for each factor. | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline to 6 Week and 24 Week Endpoints in the Hamilton 17-Items Depression Scale (HAMD-17) Total Score | The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (not at all depressed) to 52 (severely depressed). | Baseline, 6 Weeks, 24 Weeks | 
| Mean Change From Baseline to 6 Week and 24 Week Endpoints in the Hamilton Anxiety Scale (HAMA) Total Score | The 14-item HAMA assesses the severity of anxiety. The investigator talked to the patient about their symptoms over the previous week before the study visit. Each item was scored using a 5-point scale, i.e. 0 = absent to 4 = severe. The total score of HAMA-14 may range from 0 (not present) to 56 (very severe). | Baseline, 6 Weeks, 24 Weeks | 
| Mean Change From Baseline to 6 Week and 24 Week Endpoints in the Young Mania Rating Scale (YMRS) Total Score | The YMRS is an 11-item scale that measures the severity of manic episodes. Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60. | Baseline, 6 Weeks, 24 Weeks | 
| Mean Change From Baseline to 24 Week Endpoint in Glycaemia Levels (Glucose Fasting Levels) |  | baseline and 24 weeks | 
| Increases and Decreases in Fasting Glucose Levels |  | over 24 weeks | 
| Mean Change From Baseline to 24 Week Endpoint in Lipids | Baseline, change from baseline, and percent change for the following lipids are presented: Total Cholesterol (TC), High Density Lipoproteins (HDL), Low Density Lipoproteins (LDL), and Triglycerides (TG). | Baseline and 24 Weeks | 
| Increases and Decreases in Lipid Levels |  | over 24 weeks | 
| Mean Change From Baseline to 24 Week Endpoint in Weight |  | Baseline and 24 weeks | 
| Weight Gain Compared to Baseline | Weight gain at anytime more than 7%-15% or 25% of body weight compared to baseline | over 24 weeks | 
| Wellness Interventional Program for Weight Gain Management in Patients (for Those Who Gain at Anytime More Than 7% of Body Weight, Compared to Baseline) |  | 24 weeks | 
| MATHYS Total Score at Baseline - According to Thymic Reactivity Assessment | A visual analogic scale consisting of 20 items. Items scores vary from 0 (inhibition of the state evaluated by the item) to 10 (excitation for the evaluated state), except for items 5 to 10 and 17 and 18, which are inversed and are consequently to be reversed before the analysis. Total score is sum of the 20 items and can vary from 0 to 200. | Baseline | 
| Change From Baseline to 6 Week and 24 Week Endpoints in HAMA Total Scores - According to Thymic Reactivity Assessment | The 14-item HAMA assesses the severity of anxiety. The investigator talked to the patient about their symptoms over the previous week before the study visit. Each item was scored using a 5-point scale, i.e. 0 = absent to 4 = severe. The total score of HAMA-14 may range from 0 (not present) to 56 (very severe). | Baseline, 6 Weeks, 24 Weeks | 
| Change From Baseline to 6 Week and 24 Week Endpoints in HAMD-17 Total Scores - According to Thymic Reactivity Assessment | The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (not at all depressed) to 52 (severely depressed). | Baseline, 6 Weeks, 24 Weeks | 
| Change From Baseline to 6 Week and 24 Week Endpoints in YMRS Total Scores - According to Thymic Reactivity Assessment | The YMRS is an 11-item scale that measures the severity of manic episodes. Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60. | Baseline, 6 Weeks, 24 Weeks | 
| Emotional Reactivity With the Physiological Measure of Heart Rate | to assess emotional reactivity with the physiological measure of heart rate, recorded as a function of slides sessions from the International Affective Picture System, in a defined subgroup of patients | 12 weeks | 
| Emotional Reactivity With the Physiological Measure of Skin Conductance | To assess emotional reactivity with the physiological measure of skin conductance, recorded as a function of slides sessions from the International Affective Picture System, in a defined subgroup of patients. | 12 weeks | 
| Emotional Reactivity With the Physiological Measure of Startle Reflex Response - Latency of Blink | To assess emotional reactivity with the physiological measure of startle reflex response by measuring the latency of the blink, recorded as a function of slides sessions from the International Affective Picture System, in a defined subgroup of patients. | 12 weeks | 
| Emotional Reactivity With the Physiological Measure of Startle Reflex Response - Amplitude of Blink | To assess emotional reactivity with the physiological measure of startle reflex response - by measuring the amplitude of the blink, recorded as a function of slides sessions from the International Affective Picture System, in a defined subgroup of patients. | 12 weeks |