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

Primary Purpose

Bipolar Disorder

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

divalproex ER

quetiapine

About this trial

This is an interventional treatment trial for Bipolar Disorder focused on measuring quetiapine, divalproex

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

For inclusion, patients must fulfill all of the following criteria at enrollment:

Provide written informed consent before initiation of any study-related procedures
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)
Male or female, at least 18 years old
YMRS score equal to or greater than 17 and a CGI of 4 (moderate) or greater.
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:

Known intolerance or lack of response to quetiapine fumarate or Divalproex ER as judged by the investigator.
Unwilling or not able to provide informed consent
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.
History of schizophrenia or schizoaffective disorder
Treatment with a depot antipsychotic within 1 treatment cycle
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
A female subject who is pregnant or lactating
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.
Hospitalized for more than 1 week for current episode at the screen
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.
Known diagnosis of dementia or MCI

Sites / Locations

UCSD Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

1 Divalproex ER

2 Quetiapine Fumarate

Arm Description

Divalproex ER

quetiapine fumarate

Outcomes

Primary Outcome Measures

Primary Measure: Young Mania Rating Scale (YMRS) Primary Endpoint: Day 7

Minimum: 0 Maximum: 60 Higher scores indicate worse outcome

Secondary Outcome Measures

Young Mania Rating Scale (YMRS) Secondary Endpoints

Clinical Global Impression: Severity (CGI:S)

Clinical Global Impression: Improvement (CGI:I)

Readiness to Discharge Questionnaire (RDQ)

Montgomery-Asberg Depression Rating Scale (MADRS)

Behavioral Activity Rating Scale (BARS)

Extrapyramidal Symptoms Rating Scale (ESRS)

Full Information

NCT ID

NCT00397020

First Posted

November 6, 2006

Last Updated

August 16, 2019

Sponsor

University of California, San Diego

Collaborators

Abbott

1. Study Identification

Unique Protocol Identification Number

NCT00397020

Brief Title

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

Official Title

A Single-Blind, Randomized, Naturalistic Pilot Study, Comparison of Divalproex ER and Quetiapine for Adults With Acute Mania or Mixed Episodes

Study Type

Interventional

2. Study Status

Record Verification Date

August 2019

Overall Recruitment Status

Completed

Study Start Date

December 2006 (undefined)

Primary Completion Date

December 2008 (Actual)

Study Completion Date

December 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of California, San Diego

Collaborators

Abbott

4. Oversight

Data Monitoring Committee

5. 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

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. Depakote® 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Bipolar Disorder

Keywords

quetiapine, divalproex

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

Outcomes Assessor

Allocation

Randomized

Enrollment

30 (Actual)

8. Arms, Groups, and Interventions

Arm Title

1 Divalproex ER

Arm Type

Experimental

Arm Description

Divalproex ER

Arm Title

2 Quetiapine Fumarate

Arm Type

Active Comparator

Arm Description

quetiapine fumarate

Intervention Type

Drug

Intervention Name(s)

divalproex ER

Other Intervention Name(s)

Depakote ER

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

quetiapine

Other Intervention Name(s)

Seroquel

Intervention Description

Dose: 200mg PO QHS, titrated up to therapeutic dose of 600-800mg.

Primary Outcome Measure Information:

Title

Primary Measure: Young Mania Rating Scale (YMRS) Primary Endpoint: Day 7

Description

Minimum: 0 Maximum: 60 Higher scores indicate worse outcome

Time Frame

Day 7

Secondary Outcome Measure Information:

Title

Young Mania Rating Scale (YMRS) Secondary Endpoints

Time Frame

weekly - Day 3, 14, 21

Title

Clinical Global Impression: Severity (CGI:S)

Time Frame

each visit

Title

Clinical Global Impression: Improvement (CGI:I)

Time Frame

each week/visit

Title

Readiness to Discharge Questionnaire (RDQ)

Time Frame

each week/visit in the hospital

Title

Montgomery-Asberg Depression Rating Scale (MADRS)

Time Frame

each week/visit

Title

Behavioral Activity Rating Scale (BARS)

Time Frame

each week/visit

Title

Extrapyramidal Symptoms Rating Scale (ESRS)

Time Frame

each week/visit

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: For inclusion, patients must fulfill all of the following criteria at enrollment: Provide written informed consent before initiation of any study-related procedures 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) Male or female, at least 18 years old YMRS score equal to or greater than 17 and a CGI of 4 (moderate) or greater. 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: Known intolerance or lack of response to quetiapine fumarate or Divalproex ER as judged by the investigator. Unwilling or not able to provide informed consent 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. History of schizophrenia or schizoaffective disorder Treatment with a depot antipsychotic within 1 treatment cycle 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 A female subject who is pregnant or lactating 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. Hospitalized for more than 1 week for current episode at the screen 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. Known diagnosis of dementia or MCI

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David Feifel, MD, PhD

Organizational Affiliation

UCSD

Official's Role

Principal Investigator

Facility Information:

Facility Name

UCSD Medical Center

City

San Diego

State/Province

California

ZIP/Postal Code

92103

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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