Clinical Neurobiology of Serotonin and Addiction

• ClinicalTrials.gov Identifier: NCT00732901
• Recruitment Status: Completed
• First Posted: August 12, 2008
• Results First Posted: March 30, 2017
• Last Update Posted: March 8, 2019
• Sponsor: Virginia Commonwealth University
• Collaborators: National Institute on Drug Abuse (NIDA); The University of Texas Health Science Center, Houston
• Information provided by (Responsible Party): Virginia Commonwealth University

Tracking Information

• First Submitted Date: August 8, 2008
• First Posted Date: August 12, 2008
• Results First Submitted Date: July 20, 2016
• Results First Posted Date: March 30, 2017
• Last Update Posted Date: March 8, 2019
• Study Start Date: June 2008
• Actual Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 10, 2017)

Immediate Memory Task [ Time Frame: after acute dose and after chronic administration ]

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.

• Original Primary Outcome Measures (submitted: August 8, 2008): impulsivity [ Time Frame: 5 weeks of treatment ]

Current Secondary Outcome Measures (submitted: February 10, 2017)

• Attentional Bias as Measured by the Cocaine Stroop Task. [ Time Frame: 5 weeks of treatment ]
  Attentional bias is the difference in reaction time to cocaine related words and neutral words. A slower reaction time indicates greater attentional bias.
• Cocaine Positive Urines [ Time Frame: 5 weeks of treatment ]
  Number of urine drug screens positive for cocaine metabolite benzoylecgonine.

Original Secondary Outcome Measures (submitted: August 8, 2008)

• cue reactivity [ Time Frame: 5 weeks of treatment ]
• cocaine positive urines [ Time Frame: 5 weeks of treatment ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Clinical Neurobiology of Serotonin and Addiction
• Official Title: Project 1: Clinical Neurobiology of Serotonin and Addiction
• Brief 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.

Detailed 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.

• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Basic Science
• Condition: Cocaine Dependence

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
  Other Name: Lexapro
• Drug: Placebo
  Once daily days 1-28

Study Arms

• Experimental: A (escitalopram)
  Escitalopram
  Intervention: Drug: Escitalopram
• Experimental: B (placebo)
  Placebo
  Intervention: Drug: Placebo

Publications *

• 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: 10.3109/00952990.2010.543204. Epub 2011 Jan 5.
• 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:e369. doi: 10.1038/tp.2013.131.
• 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: 10.1177/0269881113492898. Epub 2013 Jun 12.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 8, 2008): 160
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: February 2013
• Actual Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00732901
• Other Study ID Numbers: HM15289 - 2; P20DA024157 ( U.S. NIH Grant/Contract ); DA 024157 ( Other Identifier )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Virginia Commonwealth University
• Original Responsible Party: Frederick Gerard Moeller, MD, The University of Texas Health Science Center-Houston
• Current Study Sponsor: Virginia Commonwealth University
• Original Study Sponsor: National Institute on Drug Abuse (NIDA)

Collaborators

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

Investigators

• Principal Investigator: Frederick G Moeller, MD; The University of Texas Health Science Center, Houston

• PRS Account: Virginia Commonwealth University
• Verification Date: June 2017