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| ID | Type | Description | Link |
|---|---|---|---|
| R01MH069801 | U.S. NIH Grant/Contract | View source | |
| DSIR 83-ATSO |
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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
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This study will determine the effectiveness of three different drug therapies in treating the symptoms of mania.
Mania is a serious condition characterized by extreme excitement, mental and physical hyperactivity, insomnia, and disconnected thoughts. Symptoms of mania are common in patients with schizophrenia or bipolar disorder. When associated with these conditions, mania reaches psychotic proportions and often includes hallucinations, paranoia, and feelings of omnipotence. Such symptoms may put individuals with mania and those around them at risk for physical harm. Drug therapies that can safely and effectively treat symptoms of mania are needed. This study will compare three drug combinations in their ability to treat symptoms of mania in people with schizophrenia or bipolar I disorder.
This study will comprise a 12-week acute phase and a 14-week continuation phase. While the acute phase is the primary component of this study, the continuation phase will provide extended data on the characteristics and course of responders to the initial treatment combinations. Results from the continuation phase will be reported elsewhere. In the acute phase, participants will be randomly assigned to receive one of three treatments: divalproex-extended release (DV-ER) and lithium, DV-ER and quetiapine, or DV-ER and placebo. Participants will receive their intervention for 12 weeks. Participants will have weekly study visits for the first 4 weeks of the acute phase; biweekly study visits will occur for the following 8 weeks. After the acute phase, participants who have not responded to their drug regimen will complete their participation in the study.
Participants whose symptoms of mania have decreased will be offered enrollment in the 14-week continuation phase, during which time participants will continue the drug regimen they began in the acute phase. Participants will have biweekly study visits in the continuation phase. During each study visit in both phases, participants will be interviewed about their mania symptoms. Mania, depression, quality of life, and overall functioning scales will assess participants at study entry, at the end of the acute phase, and at the end of the continuation phase. Participants over 50 years of age will have an electrocardiogram (EKG) at study entry to determine cardiac function.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DVP + placebo | Placebo Comparator | Participants will receive divalproex ER at a therapeutic dose, plus placebo |
|
| DVP + Quetiapine | Active Comparator | Participants will receive divalproex ER at a therapeutic dose, plus quetiapine up to 800 mg |
|
| DVP + Lithium | Active Comparator | Participants will receive divalproex ER at a therapeutic dose, plus lithium at a therapeutic blood level |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Divalproex-extended release (DVP-ER) | Drug | Divalproex ER will be given in 250 mg or 500 mg tablets. Dosing is once a day, every day, for the duration of study participation, either 12 or 26 weeks. |
| Measure | Description | Time Frame |
|---|---|---|
| Symptoms of Mania, as Measured by Young Mania Rating Scale | Symptoms of mania, as measured by Young Mania Rating Scale. The scale is eleven-item multiple choice diagnostic questionnaire (range 0-60), which psychiatrists use to measure the severity of manic episodes in children and young adults. Typically, 20 is the minimum score required for mania. Higher scores represent increased severity of mania symptoms. | Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Hamilton Rating Scale for Depression (HAM-D,17) | The Hamilton Rating Scale for Depression is a multiple item questionnaire used to provide an indication of depression, and as a guide to evaluate recovery. The questionnaire is designed for adults and is used to rate the severity of their depression by probing mood, feelings of guilt, suicide ideation, insomnia, agitation or retardation, anxiety, weight loss, and somatic symptoms. The 17-item Likert-type scale (range 0-50) includes eight questions with a 5-point scale (ranging from 0=not present to 4=severe) and nine items scored from 0 to 2. Higher scores indicate increased depression severity. The total sum of these 17 answers is used to arrive at the final score: normal (0-7), mild (8-13), moderate (14-18), severe (19-22), or very severe (>=23). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Trisha Suppes, MD, PhD | Stanford School of Medicine and VA Palo Alto Health Care System | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| VA Palo Alto Health Care System | Palo Alto | California | 94304 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35235061 | Derived | Cosgrove VE, Allende S, Gwizdowski I, Grace Fischer E, Ostacher M, Suppes T. A pilot trial of quetiapine, lithium, or placebo added to divalproex sodium for hypomanic or manic episodes in ambulatory adults with bipolar I disorder. Int J Bipolar Disord. 2022 Mar 2;10(1):7. doi: 10.1186/s40345-022-00252-w. |
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| ID | Title | Description |
|---|---|---|
| FG000 | DVP + Placebo | Participants will receive divalproex ER at a therapeutic dose, plus placebo Divalproex-extended release (DVP-ER): Divalproex ER will be given in 250 mg or 500 mg tablets. Dosing is once a day, every day, for the duration of study participation, either 12 or 26 weeks. |
| FG001 | DVP + Quetiapine | Participants will receive divalproex ER at a therapeutic dose, plus quetiapine up to 800 mg Divalproex-extended release (DVP-ER): Divalproex ER will be given in 250 mg or 500 mg tablets. Dosing is once a day, every day, for the duration of study participation, either 12 or 26 weeks. Quetiapine: Quetiapine will be dosed to efficacy, provided in 50 mg, 100 mg, 200 mg, or 300 mg pills. |
| FG002 | DVP + Lithium | Participants will receive divalproex ER at a therapeutic dose, plus lithium at a therapeutic blood level Divalproex-extended release (DVP-ER): Divalproex ER will be given in 250 mg or 500 mg tablets. Dosing is once a day, every day, for the duration of study participation, either 12 or 26 weeks. Lithium: Extended release lithium will be provided in 300 mg capsules. Participants will be dosed to a therapeutic blood level of lithium from 0.8 to 1.2 mcg/L. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | DVP + Placebo | Participants will receive divalproex ER at a therapeutic dose, plus placebo Divalproex-extended release (DVP-ER): Divalproex ER will be given in 250 mg or 500 mg tablets. Dosing is once a day, every day, for the duration of study participation, either 12 or 26 weeks. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Symptoms of Mania, as Measured by Young Mania Rating Scale | Symptoms of mania, as measured by Young Mania Rating Scale. The scale is eleven-item multiple choice diagnostic questionnaire (range 0-60), which psychiatrists use to measure the severity of manic episodes in children and young adults. Typically, 20 is the minimum score required for mania. Higher scores represent increased severity of mania symptoms. | Posted | Mean | Standard Deviation | units on a scale | Week 12 |
|
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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 | DVP + Placebo | Participants will receive divalproex ER at a therapeutic dose, plus placebo Divalproex-extended release (DVP-ER): Divalproex ER will be given in 250 mg or 500 mg tablets. Dosing is once a day, every day, for the duration of study participation, either 12 or 26 weeks. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Increased Appetite | Metabolism and nutrition disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Patricia Suppes | Stanford University | 6504935000 | 62567 | tsuppes@Stanford.edu |
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| ID | Term |
|---|---|
| D001714 | Bipolar Disorder |
| D012559 | Schizophrenia |
| D000087122 | Mania |
| D011618 | Psychotic Disorders |
| ID | Term |
|---|---|
| D000068105 | Bipolar and Related Disorders |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
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| ID | Term |
|---|---|
| D014635 | Valproic Acid |
| D008094 | Lithium |
| D016651 | Lithium Carbonate |
| D000069348 | Quetiapine Fumarate |
| ID | Term |
|---|---|
| D010421 | Pentanoic Acids |
| D014631 | Valerates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
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|
| Lithium | Drug | Extended release lithium will be provided in 300 mg capsules. Participants will be dosed to a therapeutic blood level of lithium from 0.8 to 1.2 mcg/L. |
|
|
| Quetiapine | Drug | Quetiapine will be dosed to efficacy, provided in 50 mg, 100 mg, 200 mg, or 300 mg pills. |
|
|
| Week 12 |
| Clinical Global Impression Scale for Bipolar Disorder (CGI-BD) | The Clinical Global Impression (CGI) rating scale was modified by Spearing and colleagues (1997) for use in bipolar disorder. CGI scales are measures of symptom severity, treatment response and the efficacy of treatments in treatment studies of patients with mental disorders. The revised CGI-Bipolar Version (CGI-BP) is effective in rating severity of manic and depressive episodes and the degree of change from the immediately preceding phase and from the worst phase of illness. The CGI-BP is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal, not ill) to 7 (very severely ill). Each component of the CGI is rated separately; the instrument does not yield a global score. Only severity of illness scores are reported. Increased scores represent increased illness severity | Week 12 |
| Global Assessment of Functioning | The Global Assessment of Functioning (GAF) is a numeric scale used by mental health clinicians and physicians to rate subjectively the social, occupational, and psychological functioning of an individual, e.g., how well one is meeting various problems-in-living. Scores range from 100 (extremely high functioning) to 1 (severely impaired). | Week 12 |
| Social and Occupational Functioning Assessment Scale (SOFAS) | The Social and Occupational Functioning Assessment Scale (SOFAS) provides a rating of global social and occupational function independent of clinical symptoms. SOFAS is provided in the Diagnostic and Statistical Manual (DSM-IV) as an Axis V measure. The SOFAS is a global rating of current functioning, which is scored positively on a scale from 0 to 100. Higher scores represent higher levels of functioning. This instrument is a one-item rating of consumer functioning. | Week 12 |
| DVP + Quetiapine |
Participants will receive divalproex ER at a therapeutic dose, plus quetiapine up to 800 mg Divalproex-extended release (DVP-ER): Divalproex ER will be given in 250 mg or 500 mg tablets. Dosing is once a day, every day, for the duration of study participation, either 12 or 26 weeks. Quetiapine: Quetiapine will be dosed to efficacy, provided in 50 mg, 100 mg, 200 mg, or 300 mg pills. |
| BG002 | DVP + Lithium | Participants will receive divalproex ER at a therapeutic dose, plus lithium at a therapeutic blood level Divalproex-extended release (DVP-ER): Divalproex ER will be given in 250 mg or 500 mg tablets. Dosing is once a day, every day, for the duration of study participation, either 12 or 26 weeks. Lithium: Extended release lithium will be provided in 300 mg capsules. Participants will be dosed to a therapeutic blood level of lithium from 0.8 to 1.2 mcg/L. |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Mean Number of Lifetime Episodes of Depression | Mean | Standard Deviation | episodes of depression |
|
Participants will receive divalproex ER at a therapeutic dose, plus quetiapine up to 800 mg Divalproex-extended release (DVP-ER): Divalproex ER will be given in 250 mg or 500 mg tablets. Dosing is once a day, every day, for the duration of study participation, either 12 or 26 weeks. Quetiapine: Quetiapine will be dosed to efficacy, provided in 50 mg, 100 mg, 200 mg, or 300 mg pills. |
| OG002 | DVP + Lithium | Participants will receive divalproex ER at a therapeutic dose, plus lithium at a therapeutic blood level Divalproex-extended release (DVP-ER): Divalproex ER will be given in 250 mg or 500 mg tablets. Dosing is once a day, every day, for the duration of study participation, either 12 or 26 weeks. Lithium: Extended release lithium will be provided in 300 mg capsules. Participants will be dosed to a therapeutic blood level of lithium from 0.8 to 1.2 mcg/L. |
|
|
| Secondary | Hamilton Rating Scale for Depression (HAM-D,17) | The Hamilton Rating Scale for Depression is a multiple item questionnaire used to provide an indication of depression, and as a guide to evaluate recovery. The questionnaire is designed for adults and is used to rate the severity of their depression by probing mood, feelings of guilt, suicide ideation, insomnia, agitation or retardation, anxiety, weight loss, and somatic symptoms. The 17-item Likert-type scale (range 0-50) includes eight questions with a 5-point scale (ranging from 0=not present to 4=severe) and nine items scored from 0 to 2. Higher scores indicate increased depression severity. The total sum of these 17 answers is used to arrive at the final score: normal (0-7), mild (8-13), moderate (14-18), severe (19-22), or very severe (>=23). | Posted | Mean | Standard Deviation | units on a scale | Week 12 |
|
|
|
| Secondary | Clinical Global Impression Scale for Bipolar Disorder (CGI-BD) | The Clinical Global Impression (CGI) rating scale was modified by Spearing and colleagues (1997) for use in bipolar disorder. CGI scales are measures of symptom severity, treatment response and the efficacy of treatments in treatment studies of patients with mental disorders. The revised CGI-Bipolar Version (CGI-BP) is effective in rating severity of manic and depressive episodes and the degree of change from the immediately preceding phase and from the worst phase of illness. The CGI-BP is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal, not ill) to 7 (very severely ill). Each component of the CGI is rated separately; the instrument does not yield a global score. Only severity of illness scores are reported. Increased scores represent increased illness severity | Posted | Mean | Standard Deviation | units on a scale | Week 12 |
|
|
|
| Secondary | Global Assessment of Functioning | The Global Assessment of Functioning (GAF) is a numeric scale used by mental health clinicians and physicians to rate subjectively the social, occupational, and psychological functioning of an individual, e.g., how well one is meeting various problems-in-living. Scores range from 100 (extremely high functioning) to 1 (severely impaired). | Posted | Mean | Standard Deviation | units on a scale | Week 12 |
|
|
|
| Secondary | Social and Occupational Functioning Assessment Scale (SOFAS) | The Social and Occupational Functioning Assessment Scale (SOFAS) provides a rating of global social and occupational function independent of clinical symptoms. SOFAS is provided in the Diagnostic and Statistical Manual (DSM-IV) as an Axis V measure. The SOFAS is a global rating of current functioning, which is scored positively on a scale from 0 to 100. Higher scores represent higher levels of functioning. This instrument is a one-item rating of consumer functioning. | Posted | Mean | Standard Deviation | units on a scale | Week 12 |
|
|
|
| 0 |
| 24 |
| 7 |
| 24 |
| EG001 | DVP + Quetiapine | Participants will receive divalproex ER at a therapeutic dose, plus quetiapine up to 800 mg Divalproex-extended release (DVP-ER): Divalproex ER will be given in 250 mg or 500 mg tablets. Dosing is once a day, every day, for the duration of study participation, either 12 or 26 weeks. Quetiapine: Quetiapine will be dosed to efficacy, provided in 50 mg, 100 mg, 200 mg, or 300 mg pills. | 0 | 26 | 1 | 26 |
| EG002 | DVP + Lithium | Participants will receive divalproex ER at a therapeutic dose, plus lithium at a therapeutic blood level Divalproex-extended release (DVP-ER): Divalproex ER will be given in 250 mg or 500 mg tablets. Dosing is once a day, every day, for the duration of study participation, either 12 or 26 weeks. Lithium: Extended release lithium will be provided in 300 mg capsules. Participants will be dosed to a therapeutic blood level of lithium from 0.8 to 1.2 mcg/L. | 0 | 25 | 1 | 25 |
| Sedation | General disorders | Systematic Assessment |
|
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| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009930 |
| Organic Chemicals |
| D005232 | Fatty Acids, Volatile |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D008672 | Metals, Alkali |
| D004602 | Elements |
| D007287 | Inorganic Chemicals |
| D019565 | Metals, Light |
| D008670 | Metals |
| D002254 | Carbonates |
| D000468 | Alkalies |
| D002255 | Carbonic Acid |
| D017554 | Carbon Compounds, Inorganic |
| D018020 | Lithium Compounds |
| D003987 | Dibenzothiazepines |
| D013841 | Thiazepines |
| D013846 | Thiepins |
| D013457 | Sulfur Compounds |
| D006575 | Heterocyclic Compounds, 3-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |