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

This study has been completed.
Sponsor:
Collaborator:
Abbott
Information provided by:
University of California, San Diego
ClinicalTrials.gov Identifier:
NCT00397020
First received: November 6, 2006
Last updated: June 3, 2009
Last verified: June 2009
  Purpose

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 Intervention Phase
Bipolar Disorder
Drug: divalproex ER
Drug: quetiapine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (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

Resource links provided by NLM:


Further study details as provided by University of California, San Diego:

Primary Outcome Measures:
  • Primary Measure: Young Mania Rating Scale (YMRS) Primary Endpoint: Day 7 [ Time Frame: one week or since last visit ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Young Mania Rating Scale (YMRS) Secondary endpoints [ Time Frame: weekly - Day 3, 14, 21 ] [ Designated as safety issue: No ]
  • Clinical Global Impression: Severity (CGI:S) [ Time Frame: each visit ] [ Designated as safety issue: No ]
  • Clinical Global Impression: Improvement (CGI:I) [ Time Frame: each week/visit ] [ Designated as safety issue: No ]
  • Readiness to Discharge Questionnaire (RDQ) [ Time Frame: each week/visit in the hospital ] [ Designated as safety issue: No ]
  • Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: each week/visit ] [ Designated as safety issue: No ]
  • Behavioral Activity Rating Scale (BARS) [ Time Frame: each week/visit ] [ Designated as safety issue: Yes ]
  • Extrapyramidal Symptoms Rating Scale (ESRS) [ Time Frame: each week/visit ] [ Designated as safety issue: Yes ]

Enrollment: 39
Study Start Date: December 2006
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Divalproex ER
Divalproex ER
Drug: divalproex ER
Other Name: Depakote ER
Active Comparator: 2 Quetiapine Fumarate
quetiapine fumarate
Drug: quetiapine
Other Name: Seroquel

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00397020

Locations
United States, California
UCSD Medical Center
San Diego, California, United States, 92103
Sponsors and Collaborators
University of California, San Diego
Abbott
Investigators
Principal Investigator: David Feifel, MD, PhD UCSD
  More Information

No publications provided

Responsible Party: Dr.Feifel, UCSD Medical Center
ClinicalTrials.gov Identifier: NCT00397020     History of Changes
Other Study ID Numbers: Bipolar Mania
Study First Received: November 6, 2006
Last Updated: June 3, 2009
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Diego:
quetiapine
divalproex

Additional relevant MeSH terms:
Bipolar Disorder
Affective Disorders, Psychotic
Mental Disorders
Mood Disorders
Quetiapine
Antipsychotic Agents
Central Nervous System Agents
Central Nervous System Depressants
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on November 20, 2014