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

• ClinicalTrials.gov Identifier: NCT00259272
• Recruitment Status: Completed
• First Posted: November 29, 2005
• Results First Posted: June 24, 2009
• Last Update Posted: June 24, 2009
• Sponsor: Eli Lilly and Company
• Information provided by: Eli Lilly and Company

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Bipolar Disorder I or II	Drug: olanzapine	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 141 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Study Start Date: November 2005
• Actual Primary Completion Date: May 2008
• Actual Study Completion Date: May 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: A	Drug: olanzapine; 5 to 20 mg (flexible dose) administered orally as disintegrated tablets, daily for 24 weeks.; Other Names: LY170053; Velotab; Zydis

Outcome Measures

Primary Outcome Measures :

1. Mean Changes From Baseline to 6 Week and 24 Week Endpoints in the Multidimensional Assessment of THYmic States Scale (MATHYS) Total Score [ Time Frame: Baseline, 6 Weeks, 24 weeks ]
   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.
2. Baseline MATHYS Assessment - Principal Component Analysis and Orthogonal Transformation Matrix [ Time Frame: Baseline ]
   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.

Secondary Outcome Measures :

1. Mean Change From Baseline to 6 Week and 24 Week Endpoints in the Hamilton 17-Items Depression Scale (HAMD-17) Total Score [ Time Frame: Baseline, 6 Weeks, 24 Weeks ]
   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).
2. Mean Change From Baseline to 6 Week and 24 Week Endpoints in the Hamilton Anxiety Scale (HAMA) Total Score [ Time Frame: Baseline, 6 Weeks, 24 Weeks ]
   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).
3. Mean Change From Baseline to 6 Week and 24 Week Endpoints in the Young Mania Rating Scale (YMRS) Total Score [ Time Frame: Baseline, 6 Weeks, 24 Weeks ]
   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.
4. Mean Change From Baseline to 24 Week Endpoint in Glycaemia Levels (Glucose Fasting Levels) [ Time Frame: baseline and 24 weeks ]
5. Increases and Decreases in Fasting Glucose Levels [ Time Frame: over 24 weeks ]
6. Mean Change From Baseline to 24 Week Endpoint in Lipids [ Time Frame: Baseline and 24 Weeks ]
   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).
7. Increases and Decreases in Lipid Levels [ Time Frame: over 24 weeks ]
8. Mean Change From Baseline to 24 Week Endpoint in Weight [ Time Frame: Baseline and 24 weeks ]
9. Weight Gain Compared to Baseline [ Time Frame: over 24 weeks ]
   Weight gain at anytime more than 7%-15% or 25% of body weight compared to baseline
10. Wellness Interventional Program for Weight Gain Management in Patients (for Those Who Gain at Anytime More Than 7% of Body Weight, Compared to Baseline) [ Time Frame: 24 weeks ]
11. MATHYS Total Score at Baseline - According to Thymic Reactivity Assessment [ Time Frame: Baseline ]
    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.
12. Change From Baseline to 6 Week and 24 Week Endpoints in HAMA Total Scores - According to Thymic Reactivity Assessment [ Time Frame: Baseline, 6 Weeks, 24 Weeks ]
    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).
13. Change From Baseline to 6 Week and 24 Week Endpoints in HAMD-17 Total Scores - According to Thymic Reactivity Assessment [ Time Frame: Baseline, 6 Weeks, 24 Weeks ]
    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).
14. Change From Baseline to 6 Week and 24 Week Endpoints in YMRS Total Scores - According to Thymic Reactivity Assessment [ Time Frame: Baseline, 6 Weeks, 24 Weeks ]
    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.
15. Emotional Reactivity With the Physiological Measure of Heart Rate [ Time Frame: 12 weeks ]
    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
16. Emotional Reactivity With the Physiological Measure of Skin Conductance [ Time Frame: 12 weeks ]
    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.
17. Emotional Reactivity With the Physiological Measure of Startle Reflex Response - Latency of Blink [ Time Frame: 12 weeks ]
    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.
18. Emotional Reactivity With the Physiological Measure of Startle Reflex Response - Amplitude of Blink [ Time Frame: 12 weeks ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. 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).
2. Patients must be more than 18 of age at Visit 0.

Exclusion Criteria:

1. A valid current or lifetime DSM-IV-TR Axis I or II diagnosis which could interfere, at the investigator's opinion, with the evaluation.
2. 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.

Contacts and Locations

Locations

France

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Andilly, France, 95580

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Bordeaux, France, 33076

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Cornebarrieu, France, 31700

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Creteil, France, 94010

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La Rochelle, France, 17000

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La Seyne Sur Mer, France, 83500

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Lyon, France, 69322

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Marseille, France, 13385

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Montpellier, France, 34094

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Nimes, France, 30029

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Orvault, France, 44700

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Paris, France, 75019

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Pin Balma, France, 31130

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Plaisir, France, 78373

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Poitiers, France, 86021

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Toulouse, France, 31300

Sponsors and Collaborators

Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9 AM - 5 PM Eastern time (UTC/GMT-5 hours, EST); Eli Lilly and Company

More Information

• Responsible Party: Chief Medical Officer, Eli Lilly
• ClinicalTrials.gov Identifier: NCT00259272
• Other Study ID Numbers: 9675; F1D-FP-S057
• First Posted: November 29, 2005
• Results First Posted: June 24, 2009
• Last Update Posted: June 24, 2009
• Last Verified: April 2009

Additional relevant MeSH terms:

Bipolar Disorder; Bipolar and Related Disorders; Mental Disorders; Olanzapine; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents