Brain Function and Structure in Cocaine Dependence

• Sponsor: Virginia Commonwealth University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02080832
• Collaborator: The University of Texas Health Science Center, Houston (Other), National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 54
• Location: 1
• Arms: 3
• Actual Duration (Months): 72
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The purpose of this study is to examine the role of brain MRI findings in predicting treatment outcomes among individuals with cocaine dependence.

Condition or Disease	Intervention/Treatment	Phase
Cocaine Dependence	Drug: Citalopram; Drug: Placebo	Phase 2

Detailed Description

The Specific Aims of this project are:

Aim 1: To determine whether pretreatment brain activation on fMRI while performing a Go-Nogo task predicts response to pharmacotherapy in cocaine dependent subjects.

Hypothesis related to Aim 1:

Pretreatment fMRI BOLD activation in cocaine dependent subjects during impulsive responding on the Go-Nogo task predicts 8-week outcome from medication known to enhance serotonin function (citalopram). The regression coefficient of TES on pretreatment mean BOLD activation on the Go-Nogo task will be significantly greater for the citalopram group than the placebo group.

Aim 2: To determine whether pretreatment brain activation on fMRI while performing an attentional bias (cocaine Stroop) task predicts response to pharmacotherapy in cocaine dependent subjects.

Hypothesis related to Aim 2:

Pretreatment fMRI BOLD activation in cocaine dependent subjects during cocaine related words on the cocaine Stroop task predicts 8-week outcome from medication known to enhance serotonin function (citalopram). The regression coefficient of TES on pretreatment mean BOLD activation from the cocaine Stroop task will be significantly greater for the citalopram group than the placebo group.

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Brain Function and Structure in Cocaine Dependence
• Actual Study Start Date: Feb 1, 2010
• Actual Primary Completion Date: Feb 1, 2016
• Actual Study Completion Date: Feb 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Medication (Citalopram 20mg) Citalopram (20mg dose)	Drug: Citalopram; 20 mg or 40 mg daily for 8 weeks; Other Names: Celexa Citalopram HBr
Placebo Comparator: Placebo	Drug: Placebo; Placebo daily for 8 weeks
Experimental: Medication (Citalopram 40mg) Citalopram 40mg dose	Drug: Citalopram; 20 mg or 40 mg daily for 8 weeks; Other Names: Celexa Citalopram HBr

Outcome Measures

Primary Outcome Measures

1. Cocaine Use/Treatment Effectiveness Score (TES) [8 weeks of treatment]

   Number of benzoylecgonine negative urines divided by the total number of urines collected

Other Outcome Measures

1. fMRI Brain Activation in Right Inferior Frontal Gyrus [Baseline]

   Brain activation on fMRI while participants undergo a Go/Nogo task. Percent of significant cluster in Statistical Parametric Mapping (SPM) for contrast of Hard Nogo minus Easy Nogo correlation with treatment effectiveness score.

2. fMRI Brain Activation in Right Precentral Gyrus [Baseline]

   Brain activation on fMRI while participants undergo a Go/Nogo task. Percent of significant cluster in Statistical Parametric Mapping (SPM) for contrast of Hard Nogo minus Easy Nogo correlation with treatment effectiveness score.

3. fMRI Brain Activation in Right Orlandic Operculum [Baseline]

   Brain activation on fMRI while participants undergo a Go/Nogo task. Percent of significant cluster in Statistical Parametric Mapping (SPM) for contrast of Hard Nogo minus Easy Nogo correlation with treatment effectiveness score.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male and female subjects age 18 to 50 who meet current DSM-IV criteria for cocaine dependence who are seeking treatment.

Exclusion Criteria:

1. Current DSM-IV diagnosis of any psychoactive substance dependence other than cocaine, marijuana, nicotine, or alcohol

2. Have a DSM-IV axis I psychiatric disorder or neurological disease or disorder requiring ongoing treatment and/or making study participation unsafe

3. Significant current suicidal or homicidal ideation

4. Medical conditions contraindicating citalopram pharmacotherapy (liver disease, seizure disorder, bleeding disorder, or prolonged QT interval on EKG)

5. Taking CNS active concomitant medications

6. Taking medications known to have significant drug interactions with the study medication

7. Having conditions of probation or parole requiring reports of drug use to officers of the court

8. Impending incarceration

9. Pregnant or breast feeding for female patients

10. Inability to read, write, or speak English

11. Having plans to leave the immediate geographical area within 3 months

12. Unwillingness or not competent to sign a written informed consent form

13. Individuals who have pacemakers, metal or electromechanical implants or metallic foreign bodies

14. Patients who are known to be HIV positive will not be included due to possible CNS effects of HIV.

15. Alcohol withdrawal symptoms or history of significant previous alcohol withdrawal symptoms.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Virginia Commonwealth University	Richmond	Virginia	United States	23298

Sponsors and Collaborators

• Virginia Commonwealth University
• The University of Texas Health Science Center, Houston
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Frederick G Moeller, M.D., Virginia Commonwealth University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Virginia Commonwealth University
• ClinicalTrials.gov Identifier: NCT02080832
• Other Study ID Numbers: HM15378; 2P50DA009262-16A1
• First Posted: Mar 6, 2014
• Last Update Posted: Dec 26, 2017
• Last Verified: Nov 1, 2017

• Keywords provided by Virginia Commonwealth University: substance abuse; cocaine; impulsivity; serotonin; MRI
• Additional relevant MeSH terms: Cocaine-Related Disorders; Dexetimide; Citalopram

Study Results

Participant Flow

Pre-assignment Detail	For some consented participants, the imaging scan (MRI) quality was not sufficient to include those participants in the outcome analysis. These participants are captured by the"excluded from analysis by MRI" category. fMRI data was only analyzed from participants who underwent MRI scans at UT Houston which can't be combined with MRI scans at VCU.

Arm/Group Title	Medication Citalopram (20mg Dose)	Placebo	Medication Citalopram (40mg Dose)
Arm/Group Description	Citalopram (20mg dose) Citalopram: 20 mg daily for 8 weeks	Placebo: Placebo daily for 8 weeks	Citalopram (40mg dose) 40mg daily for 8 weeks
Period Title: Overall Study
STARTED	15	17	22
COMPLETED	6	5	6
NOT COMPLETED	9	12	16

Baseline Characteristics

Arm/Group Title	Medication Citalopram 20mg	Placebo	Medication Citalopram 40mg	Total
Arm/Group Description	Citalopram (20mg dose) Citalopram: 20 mg daily for 8 weeks	Placebo: Placebo daily for 8 weeks	Citalopram (40mg dose) 40mg daily for 8 weeks	Total of all reporting groups
Overall Participants	15	17	22	54
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	15 100%	17 100%	22 100%	54 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	1 6.7%	3 17.6%	5 22.7%	9 16.7%
Male	14 93.3%	14 82.4%	17 77.3%	45 83.3%
Race/Ethnicity, Customized (Count of Participants)
African American	12 80%	13 76.5%	18 81.8%	43 79.6%
Caucasian	1 6.7%	3 17.6%	2 9.1%	6 11.1%
Hispanic	2 13.3%	1 5.9%	2 9.1%	5 9.3%
Region of Enrollment (participants) [Number]
United States	15 100%	17 100%	22 100%	54 100%

Outcome Measures

1. Primary Outcome

Title	Cocaine Use/Treatment Effectiveness Score (TES)
Description	Number of benzoylecgonine negative urines divided by the total number of urines collected
Time Frame	8 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Medication (Citalopram 20mg)	Placebo	Medication (Citalopram 40mg)
Arm/Group Description	Citalopram (20mg dose) Citalopram: 20 mg or 40 mg daily for 8 weeks	Placebo: Placebo daily for 8 weeks	Citalopram 40mg dose Citalopram: 20 mg or 40 mg daily for 8 weeks
Measure Participants	6	5	6
Number [percentage of negative urines]	6.6	8.3	29

2. Other Pre-specified Outcome

Title	fMRI Brain Activation in Right Inferior Frontal Gyrus
Description	Brain activation on fMRI while participants undergo a Go/Nogo task. Percent of significant cluster in Statistical Parametric Mapping (SPM) for contrast of Hard Nogo minus Easy Nogo correlation with treatment effectiveness score.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Citalopram (20mg or 40mg)	Placebo
Arm/Group Description	Participants treated with citalopram, either 20mg or 40mg
Measure Participants	13	4
Number [Percent of significant voxels in cluster]	83	0

3. Other Pre-specified Outcome

Title	fMRI Brain Activation in Right Precentral Gyrus
Description	Brain activation on fMRI while participants undergo a Go/Nogo task. Percent of significant cluster in Statistical Parametric Mapping (SPM) for contrast of Hard Nogo minus Easy Nogo correlation with treatment effectiveness score.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Citalopram (20mg or 40mg)	Placebo
Arm/Group Description	Participants treated with citalopram, either 20mg or 40mg
Measure Participants	13	4
Number [percent of significant voxels in cluster]	9	0

4. Other Pre-specified Outcome

Title	fMRI Brain Activation in Right Orlandic Operculum
Description	Brain activation on fMRI while participants undergo a Go/Nogo task. Percent of significant cluster in Statistical Parametric Mapping (SPM) for contrast of Hard Nogo minus Easy Nogo correlation with treatment effectiveness score.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Citalopram (20mg or 40mg)	Placebo
Arm/Group Description	Participants treated with citalopram, either 20mg or 40mg
Measure Participants	13	4
Number [percent of significant voxels in cluster]	8	0

Adverse Events

Time Frame	12 weeks
Arm/Group Title	Medication (Citalopram 20mg)		Placebo		Medication (Citalopram 40mg)
Arm/Group Description	Citalopram (20mg dose) Citalopram: 20 mg or 40 mg daily for 8 weeks		Placebo: Placebo daily for 8 weeks		Citalopram 40mg dose Citalopram: 20 mg or 40 mg daily for 8 weeks
All Cause Mortality
	Medication (Citalopram 20mg)		Placebo		Medication (Citalopram 40mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/5 (0%)		0/6 (0%)
Serious Adverse Events
	Medication (Citalopram 20mg)		Placebo		Medication (Citalopram 40mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/5 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Medication (Citalopram 20mg)		Placebo		Medication (Citalopram 40mg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/5 (0%)		0/6 (0%)

Limitations/Caveats

Results should be viewed with caution due to small sample size. Data was only analyzed from participants who underwent MRI scans at UT Houston as data could not be combined with MRI scans at VCU.

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.