Clinical trial NCT00732901: Clinical Neurobiology of Serotonin and Addiction
Official title: Project 1: Clinical Neurobiology of Serotonin and Addiction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Cocaine Dependence
Keywords: substance abuse
cocaine
impulsivity
serotonin
Remeron
Mirtzapine
Lexapro
Escatilopram
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
name: The University of Texas Health Science Center, Houston
First posted: 2008-08-12
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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.

Primary outcomes:
measure: Immediate Memory Task
timeFrame: after acute dose and after chronic administration
Secondary outcomes:
measure: Attentional Bias as Measured by the Cocaine Stroop Task.
timeFrame: 5 weeks of treatment
measure: Cocaine Positive Urines
timeFrame: 5 weeks of treatment
Other outcomes:
Locations:
city: Houston
country: United States
facility: University of Texas Health Science Center-Houston; Substance Abuse Research Clinic
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: Frederick G Moeller, MD
role: PRINCIPAL_INVESTIGATOR
References:
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: 10.3109/00952990.2010.543204. Epub 2011 Jan 5.
citation: 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-HT(2)C receptor system aligns with vulnerability to cocaine cue reactivity. Transl Psychiatry. 2014 Mar 11;4(3):e369. doi: 10.1038/tp.2013.131.
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: 10.1177/0269881113492898. Epub 2013 Jun 12.