Naturalistic Study, Comparison of Divalproex Extended Release (ER) and Quetiapine for Adults With Acute Mania or Mixed Episodes

Sponsor
University of California, San Diego (Other)
Overall Status
Completed
CT.gov ID
NCT00397020
Collaborator
Abbott (Industry)
30
Enrollment
1
Location
2
Arms
24
Duration (Months)
1.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this study is to compare the efficacy and tolerability of quetiapine versus divalproex extended-release administered in a rapid oral loading fashion in the treatment of acute episodes of mania or mixed mania in bipolar disorder. Three hypotheses will be tested:

Hypothesis 1: treatment ( 3 weeks) of divalproex extended-release is similar to quetiapine in the symptomatic control of mania or mixed mania

Hypothesis 2: divalproex extended-release orally loaded may produce significant improvements in symptoms of mania sooner than quetiapine

Hypothesis 3: divalproex extended-release may produce significantly less sedation

Condition or DiseaseIntervention/TreatmentPhase
Phase 4

Detailed Description

This will be a rater-blinded, head-to-head comparison (no placebo) of divalproex ER and quetiapine in patients with symptoms of an active manic or mixed mania (symptoms of mania and depression). Forty subjects are expected to be enrolled. After screening for eligibility, eligible subjects will be randomized while hospitalized in a 1:1 ratio into 2 treatment groups: divalproex ER or quetiapine. DepakoteĀ® ER will be given orally at 30 mg/kg day initially taken at night and rounded up to nearest 500 mg dose with adjustments made through the trial as needed to obtain serum valproic acid levels of 85-125 mcg/ml. Quetiapine will be given orally at an initial dose of 200mg/day on Day 1, and titrate up to 800 mg/day. The duration of the study will be 21 days from baseline and the total number of visits including screening is five. Patients will be released from the hospital once stable and visits for the study will then take place on an outpatient basis.

Study Design

Study Type:
Interventional
Actual Enrollment :
30 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Single-Blind, Randomized, Naturalistic Pilot Study, Comparison of Divalproex ER and Quetiapine for Adults With Acute Mania or Mixed Episodes
Study Start Date :
Dec 1, 2006
Actual Primary Completion Date :
Dec 1, 2008
Actual Study Completion Date :
Dec 1, 2008

Arms and Interventions

ArmIntervention/Treatment
Experimental: 1 Divalproex ER

Divalproex ER

Drug: divalproex ER
Dose: 30mg per kg, rounded to nearest 500mg, dosed PO QHS. Adjustments made through trial to obtain serum valproic acid levels of 85-125 mcg/ml
Other Names:
  • Depakote ER
  • Active Comparator: 2 Quetiapine Fumarate

    quetiapine fumarate

    Drug: quetiapine
    Dose: 200mg PO QHS, titrated up to therapeutic dose of 600-800mg.
    Other Names:
  • Seroquel
  • Outcome Measures

    Primary Outcome Measures

    1. Primary Measure: Young Mania Rating Scale (YMRS) Primary Endpoint: Day 7 [Day 7]

      Minimum: 0 Maximum: 60 Higher scores indicate worse outcome

    Secondary Outcome Measures

    1. Young Mania Rating Scale (YMRS) Secondary Endpoints [weekly - Day 3, 14, 21]

    2. Clinical Global Impression: Severity (CGI:S) [each visit]

    3. Clinical Global Impression: Improvement (CGI:I) [each week/visit]

    4. Readiness to Discharge Questionnaire (RDQ) [each week/visit in the hospital]

    5. Montgomery-Asberg Depression Rating Scale (MADRS) [each week/visit]

    6. Behavioral Activity Rating Scale (BARS) [each week/visit]

    7. Extrapyramidal Symptoms Rating Scale (ESRS) [each week/visit]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    For inclusion, patients must fulfill all of the following criteria at enrollment:
    1. Provide written informed consent before initiation of any study-related procedures

    2. A diagnosis of Bipolar I Disorder, Most Recent Episode Manic (296.4x), or Bipolar I Disorder, Most Recent Episode Mixed (296.5x), with or without psychotic features, as defined by Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSMIV)

    3. Male or female, at least 18 years old

    4. YMRS score equal to or greater than 17 and a CGI of 4 (moderate) or greater.

    5. Female patients of childbearing potential must be using a reliable method of contraception. Reliable methods of contraception include hormonal contraceptives (e.g., oral contraceptive or long-term injectable or implantable hormonal contraceptive), double-barrier methods (e.g., condom and diaphragm, condom and foam, condom and sponge), intrauterine devices, and tubal ligation.

    Exclusion Criteria:
    1. Known intolerance or lack of response to quetiapine fumarate or Divalproex ER as judged by the investigator.

    2. Unwilling or not able to provide informed consent

    3. Positive urine toxicology result on screening for cocaine, phencyclidine (PCP), opiates or amphetamines that confirms the current manic/mixed episode is better accounted by a substance intoxication or withdrawal as judged by PI.

    4. History of schizophrenia or schizoaffective disorder

    5. Treatment with a depot antipsychotic within 1 treatment cycle

    6. Unstable medical condition including hepatic, renal, gastroenterologic, neurologic, immunologic, or hematologic diseases that is deemed by the principle investigator to likely to result in hospitalization in 6 months or death within one year

    7. A female subject who is pregnant or lactating

    8. Lorazepam will be provided for agitation and insomnia as needed for rescue only. Not to exceed 6 mg in the first 7 days; Not to exceed 4 mg for the next 3 days and note to exceed 2 mg/day for the remainder of the study. Those that require a greater amount of Lorazepam will be excluded.

    9. Hospitalized for more than 1 week for current episode at the screen

    10. Substance or alcohol dependence at enrollment and within the three months prior to enrollment (except dependence in full remission, and except for caffeine or nicotine dependence), as defined by DSM-IV criteria.

    11. Known diagnosis of dementia or MCI

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1UCSD Medical CenterSan DiegoCaliforniaUnited States92103

    Sponsors and Collaborators

    • University of California, San Diego
    • Abbott

    Investigators

    • Principal Investigator: David Feifel, MD, PhD, UCSD

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    David Feifel, Professor, University of California, San Diego
    ClinicalTrials.gov Identifier:
    NCT00397020
    Other Study ID Numbers:
    • Bipolar Mania
    First Posted:
    Nov 8, 2006
    Last Update Posted:
    Sep 11, 2019
    Last Verified:
    Aug 1, 2019
    Keywords provided by David Feifel, Professor, University of California, San Diego
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title1 Divalproex ER2 Quetiapine Fumarate
    Arm/Group DescriptionDivalproex ERquetiapine fumarate
    Period Title: Overall Study
    STARTED1416
    COMPLETED1315
    NOT COMPLETED11

    Baseline Characteristics

    Arm/Group Title1 Divalproex ER2 Quetiapine FumarateTotal
    Arm/Group DescriptionDivalproex ERquetiapine fumarateTotal of all reporting groups
    Overall Participants131528
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    13
    100%
    15
    100%
    28
    100%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    Age (years) [Mean (Full Range) ]
    Mean (Full Range) [years]
    42.4
    36.9
    39.65
    Sex: Female, Male (Count of Participants)
    Female
    5
    38.5%
    7
    46.7%
    12
    42.9%
    Male
    8
    61.5%
    8
    53.3%
    16
    57.1%
    Region of Enrollment (participants) [Number]
    United States
    13
    100%
    15
    100%
    28
    100%

    Outcome Measures

    1. Primary Outcome
    TitlePrimary Measure: Young Mania Rating Scale (YMRS) Primary Endpoint: Day 7
    DescriptionMinimum: 0 Maximum: 60 Higher scores indicate worse outcome
    Time FrameDay 7

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title1 Divalproex ER2 Quetiapine Fumarate
    Arm/Group DescriptionDivalproex ERquetiapine fumarate
    Measure Participants1015
    Mean (Standard Error) [units on a scale]
    14.8
    (2.1)
    13.9
    (1.9)
    2. Secondary Outcome
    TitleYoung Mania Rating Scale (YMRS) Secondary Endpoints
    Description
    Time Frameweekly - Day 3, 14, 21

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    3. Secondary Outcome
    TitleClinical Global Impression: Severity (CGI:S)
    Description
    Time Frameeach visit

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    4. Secondary Outcome
    TitleClinical Global Impression: Improvement (CGI:I)
    Description
    Time Frameeach week/visit

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    5. Secondary Outcome
    TitleReadiness to Discharge Questionnaire (RDQ)
    Description
    Time Frameeach week/visit in the hospital

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    6. Secondary Outcome
    TitleMontgomery-Asberg Depression Rating Scale (MADRS)
    Description
    Time Frameeach week/visit

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    7. Secondary Outcome
    TitleBehavioral Activity Rating Scale (BARS)
    Description
    Time Frameeach week/visit

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    8. Secondary Outcome
    TitleExtrapyramidal Symptoms Rating Scale (ESRS)
    Description
    Time Frameeach week/visit

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title1 Divalproex ER2 Quetiapine Fumarate
    Arm/Group DescriptionDivalproex ERquetiapine fumarate
    All Cause Mortality
    1 Divalproex ER2 Quetiapine Fumarate
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total/ (NaN) / (NaN)
    Serious Adverse Events
    1 Divalproex ER2 Quetiapine Fumarate
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/13 (0%) 0/15 (0%)
    Other (Not Including Serious) Adverse Events
    1 Divalproex ER2 Quetiapine Fumarate
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total1/13 (7.7%) 5/15 (33.3%)
    Nervous system disorders
    Neurological (fainting, dizziness, headaches)1/13 (7.7%) 15/15 (33.3%) 5

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleDr. David Feifel
    OrganizationUCSD Medical Center
    Phone619-543-2485
    Emaildfeifel@ucsd.edu
    Responsible Party:
    David Feifel, Professor, University of California, San Diego
    ClinicalTrials.gov Identifier:
    NCT00397020
    Other Study ID Numbers:
    • Bipolar Mania
    First Posted:
    Nov 8, 2006
    Last Update Posted:
    Sep 11, 2019
    Last Verified:
    Aug 1, 2019