Clinical Neurobiology of Serotonin and Addiction

Cocaine Dependence Clinical Trial

Official title:

Project 1: Clinical Neurobiology of Serotonin and Addiction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00732901
• Other study ID #: HM15289 - 2
• Secondary ID: P20DA024157DA 02
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: June 2008
• Est. completion date: February 2013

Study information

• Verified date: June 2017
• Source: Virginia Commonwealth University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to examine the relationship between 5-HT2R function, impulsivity and cue reactivity in cocaine dependent subjects and healthy controls and examine specific effects of escitalopram and mirtazapine on impulsivity and cue reactivity in human cocaine users.

Description:

Specific Aim 1: We will test the hypothesis that cocaine-dependent subjects will exhibit greater impulsivity than controls as determined by a battery of impulsivity measures and that impulsivity will be associated with specific profiles of 5-HT2AR and/or 5-HT2CR expression in platelets. We predict that treatment of cocaine-dependent subjects with escitalopram and/or mirtazapine will reduce impulsivity and cocaine-positive urines, in concert with a normalized balance of platelet 5-HT2AR and/or 5-HT2CR expression.

Specific Aim 2: We will test the hypothesis that cocaine-dependent subjects will exhibit greater cue reactivity than controls as determined by a modified Stroop task, and that cue reactivity will be associated with specific profiles of 5-HT2AR and/or 5-HT2CR expression in platelets. We predict that treatment of cocaine-dependent subjects with escitalopram and/or mirtazapine will reduce cue reactivity and cocaine-positive urines, in concert with a normalized balance of platelet 5-HT2AR and/or 5-HT2CR expression.

Specific Aim 3: We will test the hypothesis that specific polymorphisms in the 5-HT2AR and/or 5-HT2CR will predict baseline impulsivity and/or cue reactivity as well as treatment response to serotonergic medications in cocaine-dependent subjects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Non-Drug Abusing Control Subjects: Male and female subjects age 18 to 55 who do not meet current or past DSM-IV criteria for any Axis I disorder including substance abuse or dependence.

• Cocaine Dependent Subjects: Male and female subjects age 18 to 55 who meet current DSM-IV criteria for cocaine dependence.

• Female subjects: a negative pregnancy test.

Exclusion Criteria:

• Non-Drug Abusing Control Subjects:

1. Current or past DSM-IV Axis I disorder

2. Any serious non-psychiatric medical illness requiring ongoing medical treatment or which could affect the central nervous system.

3. Positive HIV test.

4. For female subjects: a positive pregnancy test or breast feeding.

5. Concomitant use of prescription medications that could affect the central nervous system.

6. Active suicidal ideation.

7. Hamilton Depression or Anxiety Scale score greater than 15

• Cocaine Dependent Subjects:

1. Current DSM-IV Axis I disorder other than substance abuse/dependence

2. Current diagnosis of other substance dependence besides cocaine.

3. Any serious non-psychiatric medical illness requiring ongoing medical treatment or which could affect the central nervous system.

4. Positive HIV test.

5. For female subjects: a positive pregnancy test or breast feeding.

6. Concomitant use of prescription medications that could affect the central nervous system.

7. Active suicidal ideation.

8. Subjects within 14 days of discontinuing a monoamine oxidase inhibitor.

9. Subjects with cardiac arrythmias.

10. Subjects with known hypersensitivity to escitalopram or citalopram, or mirtazapine

11. Hamilton Depression or Anxiety Scale score greater than 15.

12. Current alcohol abuse or dependence.

Related Conditions & MeSH terms

• Cocaine Dependence
• Cocaine-Related Disorders

Intervention

Drug:
• Escitalopram
Escitalopram: once daily 10 mg on days 1-3, 20 mg on days 4-24 and 10 mg on days 25-28
• Placebo
Once daily days 1-28

Locations

Country	Name	City	State
United States	University of Texas Health Science Center-Houston; Substance Abuse Research Clinic	Houston	Texas

Sponsors (3)

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

Country where clinical trial is conducted

United States, 

References & Publications (3)

Anastasio NC, Liu S, Maili L, Swinford SE, Lane SD, Fox RG, Hamon SC, Nielsen DA, Cunningham KA, Moeller FG. Variation within the serotonin (5-HT) 5-HT2C receptor system aligns with vulnerability to cocaine cue reactivity. Transl Psychiatry. 2014 Mar 11;4 — View Citation

Liu S, Lane SD, Schmitz JM, Cunningham KA, John VP, Moeller FG. Effects of escitalopram on attentional bias to cocaine-related stimuli and inhibitory control in cocaine-dependent subjects. J Psychopharmacol. 2013 Sep;27(9):801-7. doi: 10.1177/026988111349 — View Citation

Liu S, Lane SD, Schmitz JM, Waters AJ, Cunningham KA, Moeller FG. Relationship between attentional bias to cocaine-related stimuli and impulsivity in cocaine-dependent subjects. Am J Drug Alcohol Abuse. 2011 Mar;37(2):117-22. doi: 10.3109/00952990.2010.54 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immediate Memory Task	The IMT was used to measure impulsivity. The IMT is a continuous performance test. Subjects were instructed to respond on the computer's left mouse button when a five-digit number the target stimulus appeared that was exactly like the preceding stimulus. A catch stimulus was a number that differed only slightly from the preceding number. Only one of the five digits was changed its position and value was determined randomly. Responses errors made to catch stimuli were considered commission errors or 'false alarms'. Immediate Memory Task Commission Errors to catch stimuli were the primary measure of impulsivity in this study. Scale is percentage of overall responses to a catch stimulus that were commission errors, ranging from 0 to 100. Zero would equate to no impulsivity and 100 would equate to 100% impulsive responses.	after acute dose and after chronic administration
Secondary	Attentional Bias as Measured by the Cocaine Stroop Task.	Attentional bias is the difference in reaction time to cocaine related words and neutral words. A slower reaction time indicates greater attentional bias.	5 weeks of treatment
Secondary	Cocaine Positive Urines	Number of urine drug screens positive for cocaine metabolite benzoylecgonine.	5 weeks of treatment