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| ID | Type | Description | Link |
|---|---|---|---|
| R21MH062650 | U.S. NIH Grant/Contract | View source | |
| DSIR AT-SO |
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Funding Expiration
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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
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This study will compare triple and double drug regimens in the treatment of patients with depression, hypomania, or mania.
Early studies have shown lithium to produce a high percentage of satisfactory clinical response in patients with bipolar disorders. These studies, however, do not include lithium-refractory subgroups, such as bipolar II disorder patients. When the wide spectrum of bipolar disorders is considered, the lithium response rate decreases significantly. More broadly effective regimens are needed.
Participants in this study will be randomly assigned to receive either lithium plus divalproex or lithium, divalproex, and lamotrigine for 7 months. Symptoms of depression and mania will be assessed with scales and patient questionnaires.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lithium + divalproex + lamotrigine | Experimental |
| |
| Lithium + divalproex + placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lithium | Drug | Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over three weeks to a minimum blood level of 0.5 milliequivalent /L (mEq/L). |
|
| Measure | Description | Time Frame |
|---|---|---|
| The Proportion of Patients Who Experience a Marked and Persistent Bimodal Response | A marked bimodal response is defined by the following three conditions over four consecutive weeks while on triple therapy and after three weeks of ltg:
The MADRS measures the severity of a subject's depression symptoms with a possible total score ranging from 0 - 60, with higher scores indicating more severe depression. The YMRS measures the severity of a subject's manic symptoms with a possible total score ranging from 0 - 60, with higher scores indicating more severe mania. The GAS measures a used to rate subjectively the social, occupational, and psychological functioning of a subject and ranges in score from 0-100, with a higher score indicating better social, occupational, and psychological functioning. | Baseline and Week 28 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Keming Gao, MD, PhD | Case Western Reserve University / University Hospitals of Cleveland | Principal Investigator |
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The study was conducted by the Mood Disorders Program at Case Western Reserve University/University Hospitals Case Medical Center (Cleveland, OH, USA) from August 2002 to June 2007.
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| ID | Title | Description |
|---|---|---|
| FG000 | Lithium + Divalproex + Lamotrigine | Divalproex : Divalproex was then initiated at 250 mg twice daily and increased slowly over five weeks to a minimum blood level of 50 μg/mL. Lamotrigine : Patients were assigned in a one to one ratio to adjunctive lamotrigine versus placebo after stratification for illness type (bipolar I versus bipolar II), historical response to lithium (response versus non-response), and length of current exposure to combination treatment with lithium and divalproex (< 2 months versus ≥ 2 months). During Phase 2, patients were continued on the same doses of lithium and divalproex as during the open-label treatment phase and equal capsules of double-blind lamotrigine or matching placebo were gradually added per a structured dosing schedule up to a minimum dose of 150 mg and a maximum. dose of 200 mg per day. Lithium : Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over three weeks to a minimum blood level of 0.5 milliequivalent/L (mEq/L). |
| FG001 | Lithium + Divalproex + Placebo | Divalproex : Divalproex was then initiated at 250 mg twice daily and increased slowly over five weeks to a minimum blood level of 50 μg/mL. Lithium : Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over three weeks to a minimum blood level of 0.5 mEq/L. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Lithium + Divalproex + Lamotrigine | Divalproex : Divalproex was then initiated at 250 mg twice daily and increased slowly over five weeks to a minimum blood level of 50 μg/mL. Lamotrigine : Patients were assigned in a one to one ratio to adjunctive lamotrigine versus placebo after stratification for illness type (bipolar I versus bipolar II), historical response to lithium (response versus non-response), and length of current exposure to combination treatment with lithium and divalproex (< 2 months versus ≥ 2 months). During Phase 2, patients were continued on the same doses of lithium and divalproex as during the open-label treatment phase and equal capsules of double-blind lamotrigine or matching placebo were gradually added per a structured dosing schedule up to a minimum dose of 150 mg and a maximum. dose of 200 mg per day. Lithium : Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over three weeks to a minimum blood level of 0.5 mEq/L. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | The Proportion of Patients Who Experience a Marked and Persistent Bimodal Response | A marked bimodal response is defined by the following three conditions over four consecutive weeks while on triple therapy and after three weeks of ltg:
The MADRS measures the severity of a subject's depression symptoms with a possible total score ranging from 0 - 60, with higher scores indicating more severe depression. The YMRS measures the severity of a subject's manic symptoms with a possible total score ranging from 0 - 60, with higher scores indicating more severe mania. The GAS measures a used to rate subjectively the social, occupational, and psychological functioning of a subject and ranges in score from 0-100, with a higher score indicating better social, occupational, and psychological functioning. | Posted | Number | participants | Baseline and Week 28 |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Lithium + Divalproex + Lamotrigine | Divalproex : Divalproex was then initiated at 250 mg twice daily and increased slowly over five weeks to a minimum blood level of 50 μg/mL. Lamotrigine : Patients were assigned in a one to one ratio to adjunctive lamotrigine versus placebo after stratification for illness type (bipolar I versus bipolar II), historical response to lithium (response versus non-response), and length of current exposure to combination treatment with lithium and divalproex (< 2 months versus ≥ 2 months). During Phase 2, patients were continued on the same doses of lithium and divalproex as during the open-label treatment phase and equal capsules of double-blind lamotrigine or matching placebo were gradually added per a structured dosing schedule up to a minimum dose of 150 mg and a maximum. dose of 200 mg per day. Lithium : Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over three weeks to a minimum blood level of 0.5 mEq/L. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Itching | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Keming Gao | University Hospitals Case Medical Center | 216-844-2865 | keming.gao@UHhospitals.org |
| ID | Term |
|---|---|
| D001714 | Bipolar Disorder |
| D003863 | Depression |
| ID | Term |
|---|---|
| D000068105 | Bipolar and Related Disorders |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
| D001526 | Behavioral Symptoms |
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| ID | Term |
|---|---|
| D008094 | Lithium |
| D016651 | Lithium Carbonate |
| D000077213 | Lamotrigine |
| D014635 | Valproic Acid |
| ID | Term |
|---|---|
| D008672 | Metals, Alkali |
| D004602 | Elements |
| D007287 | Inorganic Chemicals |
| D019565 | Metals, Light |
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|
| Lamotrigine | Drug | Patients were assigned in a one to one ratio to adjunctive lamotrigine versus placebo after stratification for illness type (bipolar I versus bipolar II), historical response to lithium (response versus non-response), and length of current exposure to combination treatment with lithium and divalproex (< 2 months versus ≥ 2 months). During Phase 2, patients were continued on the same doses of lithium and divalproex as during the open-label treatment phase and equal capsules of double-blind lamotrigine or matching placebo were gradually added per a structured dosing schedule up to a minimum dose of 150 mg and a maximum dose of 200 mg per day. |
|
|
| Divalproex | Drug | Divalproex was then initiated at 250 mg twice daily and increased slowly over five weeks to a minimum blood level of 50 μg/mL. |
|
|
| Placebo | Drug | Patients were assigned in a one to one ratio to adjunctive lamotrigine versus placebo after stratification for illness type (bipolar I versus bipolar II), historical response to lithium (response versus non-response), and length of current exposure to combination treatment with lithium and divalproex (< 2 months versus ≥ 2 months). During Phase 2, patients were continued on the same doses of lithium and divalproex as during the open-label treatment phase and equal capsules of double-blind lamotrigine or matching placebo were gradually added per a structured dosing schedule up to a minimum dose of 150 mg and a maximum dose of 200 mg per day. |
|
| BG001 | Lithium + Divalproex + Placebo | Divalproex : Divalproex was then initiated at 250 mg twice daily and increased slowly over five weeks to a minimum blood level of 50 μg/mL. Lithium : Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over three weeks to a minimum blood level of 0.5 mEq/L. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Bipolar Subtype | Bipolar I Disorder is mainly defined by manic or mixed episodes that last at least seven days, or by manic symptoms that are so severe that the person needs immediate hospital care. Bipolar II Disorder is defined by a pattern of depressive episodes shifting back and forth with hypomanic episodes, but no full manic or mixed episodes | Number | participants |
|
Divalproex : Divalproex was then initiated at 250 mg twice daily and increased slowly over five weeks to a minimum blood level of 50 μg/mL. Lamotrigine : Patients were assigned in a one to one ratio to adjunctive lamotrigine versus placebo after stratification for illness type (bipolar I versus bipolar II), historical response to lithium (response versus non-response), and length of current exposure to combination treatment with lithium and divalproex (< 2 months versus ≥ 2 months). During Phase 2, patients were continued on the same doses of lithium and divalproex as during the open-label treatment phase and equal capsules of double-blind lamotrigine or matching placebo were gradually added per a structured dosing schedule up to a minimum dose of 150 mg and a maximum. dose of 200 mg per day. Lithium : Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over three weeks to a minimum blood level of 0.5 mEq/L. |
| OG001 | Lithium + Divalproex + Placebo | Divalproex : Divalproex was then initiated at 250 mg twice daily and increased slowly over five weeks to a minimum blood level of 50 μg/mL. Lithium : Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over three weeks to a minimum blood level of 0.5 mEq/L. |
|
|
| 0 |
| 23 |
| 2 |
| 23 |
| EG001 | Lithium + Divalproex + Placebo | Divalproex : Divalproex was then initiated at 250 mg twice daily and increased slowly over five weeks to a minimum blood level of 50 μg/mL. Lithium : Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over three weeks to a minimum blood level of 0.5 mEq/L. | 0 | 26 | 1 | 26 |
| Rash | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
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| D001519 |
| Behavior |
| D008670 |
| Metals |
| D002254 | Carbonates |
| D000468 | Alkalies |
| D002255 | Carbonic Acid |
| D017554 | Carbon Compounds, Inorganic |
| D018020 | Lithium Compounds |
| D014227 | Triazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D010421 | Pentanoic Acids |
| D014631 | Valerates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D005232 | Fatty Acids, Volatile |
| D005227 | Fatty Acids |
| D008055 | Lipids |