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)
• Enrollment: 30
• Location: 1
• Arms: 2
• Duration (Months): 24
• Patients Per Site Per Month: 1.2

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 Disease	Intervention/Treatment	Phase
Bipolar Disorder	Drug: divalproex ER; Drug: quetiapine	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. 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.

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

Arm	Intervention/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

	Site	City	State	Country	Postal Code
1	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

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: quetiapine; divalproex
• Additional relevant MeSH terms: Bipolar Disorder; Valproic Acid; Quetiapine Fumarate

Study Results

Participant Flow

Arm/Group Title	1 Divalproex ER	2 Quetiapine Fumarate
Arm/Group Description	Divalproex ER	quetiapine fumarate
Period Title: Overall Study
STARTED	14	16
COMPLETED	13	15
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	1 Divalproex ER	2 Quetiapine Fumarate	Total
Arm/Group Description	Divalproex ER	quetiapine fumarate	Total of all reporting groups
Overall Participants	13	15	28
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

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 Divalproex ER	2 Quetiapine Fumarate
Arm/Group Description	Divalproex ER	quetiapine fumarate
Measure Participants	10	15
Mean (Standard Error) [units on a scale]	14.8 (2.1)	13.9 (1.9)

2. Secondary Outcome

Title	Young Mania Rating Scale (YMRS) Secondary Endpoints
Time Frame	weekly - Day 3, 14, 21

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Clinical Global Impression: Severity (CGI:S)
Time Frame	each visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Clinical Global Impression: Improvement (CGI:I)
Time Frame	each week/visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Readiness to Discharge Questionnaire (RDQ)
Time Frame	each week/visit in the hospital

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Montgomery-Asberg Depression Rating Scale (MADRS)
Time Frame	each week/visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Behavioral Activity Rating Scale (BARS)
Time Frame	each week/visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Extrapyramidal Symptoms Rating Scale (ESRS)
Time Frame	each week/visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	1 Divalproex ER		2 Quetiapine Fumarate
Arm/Group Description	Divalproex ER		quetiapine fumarate
All Cause Mortality
	1 Divalproex ER		2 Quetiapine Fumarate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	1 Divalproex ER		2 Quetiapine Fumarate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	1 Divalproex ER		2 Quetiapine Fumarate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/13 (7.7%)		5/15 (33.3%)
Nervous system disorders
Neurological (fainting, dizziness, headaches)	1/13 (7.7%)	1	5/15 (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.