Valproate Efficacy in Cocaine-Bipolar Comorbidity

• Sponsor: University of Miami (Other)
• Overall Status: Completed
• CT.gov ID: NCT00240110
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 152
• Locations: 2
• Arms: 2
• Duration (Months): 96
• Patients Per Site: 76
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

This proposal will test the efficacy of a promising pharmacological approach for the treatment of comorbid cocaine dependence and bipolar disorder. We propose a randomized, double blind, placebo controlled 12-week trial to test the efficacy of Divalproex sodium (Valproate) plus treatment as usual compared to placebo plus treatment as usual in decreasing cocaine use and stabilizing mood symptoms among patients with comorbid cocaine dependence and bipolar disorder. Treatment as usual includes the use of lithium carbonate for mood stabilization plus supportive psychosocial treatment.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder; Cocaine Dependence	Drug: Valproate; Drug: Placebo; Drug: Lithium Carbonate	Phase 1/Phase 2

Detailed Description

Bipolar disorder has the highest rate of association with cocaine and other substance use disorders than any other major severe psychiatric syndrome. This comorbidity represents a major treatment challenge and is associated with severe disability, morbidity, and heightened risk for suicide.

The aims of this study are:

1. Examine the efficacy of valproate plus treatment as usual compared to placebo plus treatment as usual in decreasing cocaine use in patients with cocaine dependence and comorbid bipolar disorder.

2. Determine whether primary vs. secondary cocaine dependence, bipolar subtype (depressed vs. manic/mixed) and the presence of additional substance use disorders moderate the association between treatment and cocaine use outcome.

3. Assess the effects of medication compliance and mood symptoms as mediators of cocaine use outcome.

Study Design

• Study Type: Interventional
• Actual Enrollment: 152 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Valproate Efficacy in Cocaine-Bipolar Comorbidity
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Mar 1, 2014
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Lithium carbonate add on Placebo Lithium carbonate started and stabilized then participants randomized to placebo	Drug: Placebo; Control arm; Other Names: Placebo control ; Drug: Lithium Carbonate; All participants were started and stabilized on lithium carbonate as a standard treatment for bipolar disorder; Other Names: Standard treatment
Experimental: Lithium carbonate add on Valproate Lithium carbonate started and stabilized then participants randomized to Valproate	Drug: Valproate; Valproate with dose titration to achieve blood levels within the therapeutic range; Other Names: Divalproex sodium ; Drug: Lithium Carbonate; All participants were started and stabilized on lithium carbonate as a standard treatment for bipolar disorder; Other Names: Standard treatment

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Percentage of Cocaine-abstinent Days [Week 12]

   Change from baseline in percentage of self-report cocaine-abstinent (non-use) days (difference in base percent values)

Secondary Outcome Measures

1. Change From Baseline in Percentage of Money Spent on Cocaine [week 12]

   Change from baseline in percentage of the amount of money spent on cocaine

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Meet DSM-IV criteria for cocaine dependence and a concurrent bipolar disorder

Exclusion Criteria:

• Schizophrenia, schizoaffective, and any non-bipolar psychotic disorder, unipolar major depression, primary anxiety disorder, mental retardation, and signs of impaired cognitive functioning.

• Current DSM-IV criteria for dependence on substances other than cocaine, alcohol, cannabis, nicotine, or caffeine

• Neurological conditions including epilepsy, history of brain injury, encephalitis, or any organic brain syndrome or documented focally abnormal EEG

• Medical conditions including severe cardiac, liver, kidney, or liver disease.

• Pregnancy

• Inability or unwillingness to use contraceptive methods

• Any medical condition or other reason that in the opinion of the investigator would prevent the subject from completing the protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Miami Miller School of Medicine, Department of Psychiatry	Miami	Florida	United States	33136
2	University of Miami Miller School of Medicine	Miami	Florida	United States	33136

Sponsors and Collaborators

• University of Miami
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Ihsan M Salloum, MD, MPH, University of Miami

Study Documents (Full-Text)

None provided.

More Information

Publications

• Salloum IM, Douaihy A, Cornelius JR, Kirisci L, Kelly TM, Hayes J. Divalproex utility in bipolar disorder with co-occurring cocaine dependence: a pilot study. Addict Behav. 2007 Feb;32(2):410-5. Epub 2006 Jun 30.

• Responsible Party: Ihsan Salloum, Professor of Psychiatry, University of Miami
• ClinicalTrials.gov Identifier: NCT00240110
• Other Study ID Numbers: 20070289; R01DA019992; 05080018; DPMCDA
• First Posted: Oct 17, 2005
• Last Update Posted: Oct 17, 2016
• Last Verified: Aug 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Ihsan Salloum, Professor of Psychiatry, University of Miami: Bipolar; Cocaine; Comorbidity
• Additional relevant MeSH terms: Cocaine-Related Disorders; Bipolar Disorder; Valproic Acid; Lithium Carbonate

Study Results

Participant Flow

Pre-assignment Detail	High screen failure for not meeting inclusion/exclusion criteria and for lost to follow-up during screening

Arm/Group Title	Lithium Carbonate Add on Placebo	Lithium Carbonate Add on Valproate
Arm/Group Description	Lithium started and then participants randomized to placebo	Lithium carbonate started and participants randomized to valproate
Period Title: Overall Study
STARTED	13	13
COMPLETED	7	6
NOT COMPLETED	6	7

Baseline Characteristics

Arm/Group Title	Lithium Carbonate Add on Placebo	Lithium Carbonate Add on Valproate	Total
Arm/Group Description	Lithium carbonate started with titration to achieve blood levels within the therapeutic range and then participants randomized to placebo	Lithium carbonate started with titration to achieve blood levels within the therapeutic range and then participants randomized to valproate	Total of all reporting groups
Overall Participants	13	13	26
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	13 100%	13 100%	26 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.7 (7.4)	44 (7.7)	45.4 (7.6)
Sex: Female, Male (Count of Participants)
Female	5 38.5%	5 38.5%	10 38.5%
Male	8 61.5%	8 61.5%	16 61.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 15.4%	4 30.8%	6 23.1%
Not Hispanic or Latino	11 84.6%	9 69.2%	20 76.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	7 53.8%	7 53.8%	14 53.8%
White	6 46.2%	6 46.2%	12 46.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Percentage of Cocaine-abstinent Days
Description	Change from baseline in percentage of self-report cocaine-abstinent (non-use) days (difference in base percent values)
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

All subjects with available data after assignment to study medications

Arm/Group Title	Lithium Carbonate Add on Placebo	Lithium Carbonate Add on Valproate
Arm/Group Description	Lithium carbonate started with titration to achieve blood levels within the therapeutic range and then participants randomized to placebo	Lithium carbonate started with titration to achieve blood levels within the therapeutic range and then participants randomized to valproate
Measure Participants	11	12
Mean (Standard Deviation) [percentage of days cocaine abstinent]	16.4 (29.7)	14.5 (20.3)

2. Secondary Outcome

Title	Change From Baseline in Percentage of Money Spent on Cocaine
Description	Change from baseline in percentage of the amount of money spent on cocaine
Time Frame	week 12

Outcome Measure Data

Analysis Population Description

All subjects with available data after assignment to study medications

Arm/Group Title	Lithium Carbonate Add on Placebo	Lithium Carbonate Add on Valproate
Arm/Group Description	Open label lithium carbonate as standard treatment and double blinded placebo	Open label lithium carbonate as standard treatment and double blinded valproate
Measure Participants	11	12
Mean (Standard Deviation) [Percentage of Money Spent on Cocaine]	-43.6 (58.4)	-34.9 (56.1)

Adverse Events

Arm/Group Title	Lithium Carbonate Add on Placebo		Lithium Carbonate Add on Valproate
Arm/Group Description	Lithium carbonate as standard treatment add on double blind placebo		Lithium carbonate as standard treatment add on double blind valproate
All Cause Mortality
	Lithium Carbonate Add on Placebo		Lithium Carbonate Add on Valproate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Lithium Carbonate Add on Placebo		Lithium Carbonate Add on Valproate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		1/13 (7.7%)
Psychiatric disorders
Hospitalization	0/13 (0%)	0	1/13 (7.7%)	1
Other (Not Including Serious) Adverse Events
	Lithium Carbonate Add on Placebo		Lithium Carbonate Add on Valproate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/13 (76.9%)		10/13 (76.9%)
Cardiac disorders
Heart palpatation	1/13 (7.7%)		1/13 (7.7%)
Gastrointestinal disorders
Nausea, diarrhea	6/13 (46.2%)		6/13 (46.2%)
General disorders
Headache	4/13 (30.8%)		3/13 (23.1%)
Fall	0/13 (0%)		2/13 (15.4%)
Musculoskeletal and connective tissue disorders
Back wrist pain	3/13 (23.1%)		5/13 (38.5%)
Psychiatric disorders
Restless, sleepless	4/13 (30.8%)		5/13 (38.5%)
Renal and urinary disorders
Increased urination	3/13 (23.1%)		3/13 (23.1%)
Reproductive system and breast disorders
sexual dysfunction	1/13 (7.7%)		1/13 (7.7%)
increased menses	1/13 (7.7%)		0/13 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.