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The Effect of Yohimbine on Cocaine Cue Reactivity

Primary Purpose

Cocaine Related Disorders

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Yohimbine
Placebo
Sponsored by
Medical University of South Carolina
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cocaine Related Disorders focused on measuring Cocaine Addiction, Cocaine Dependence

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Subjects must be able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments.
  • Subjects must consent to remain abstinent from all drugs of abuse (except nicotine) for a three-day period immediately prior to the CTRC admission. Nicotine dependence can affect HPA function (Baron et al., 1995) therefore it would be ideal to exclude subjects with nicotine use. Because of the high comorbidity of cocaine and nicotine dependence, this would seriously compromise the feasibility of recruitment. Individuals with alcohol dependence will be excluded. However because of the high comorbidity of alcohol use and cocaine dependence, individuals with alcohol abuse will be included. Also, due to the high comorbidity of cocaine and marijuana dependence, and limited evidence that marijuana use affects HPA function, subjects with marijuana dependence will be included.
  • Subjects with ADHD will be included. Because ADHD is commonly characterized by impulsivity, ADHD severity ratings will be determined and controlled for in data analysis.
  • Subjects must consent to random assignment.
  • Subjects must consent to outpatient admission to the CTRC and two overnight admissions to the Medical University Hospital.

Exclusion Criteria:

  • Women who are pregnant, nursing or of childbearing potential and not practicing an effective means of birth control.
  • Women with premenstrual dysphoric disorder as this may impact on the response to the stress test procedure (Woods et al., 1994).
  • Women receiving depot medroxyprogesterone acetate as a form of birth control.
  • Subjects with evidence of or a history of significant hematological, endocrine, cardiovascular, pulmonary, renal, gastrointestinal, or neurological disease including diabetes, as these conditions may affect physiological/subjective responses.
  • Subjects with Addison's disease, Cushing's disease or other diseases of the adrenal cortex likely to affect hormonal/neuroendocrine status.
  • Subjects with a history of or current psychotic disorder or bipolar affective disorder as these may interfere with subjective measurements.
  • Subjects with current major depressive disorder or post-traumatic stress disorder as these disorders are associated with characteristic changes in stress response.
  • Subjects with panic disorder, as yohimbine may precipitate panic attacks.
  • Subjects receiving synthetic glucocorticoid therapy, any exogenous steroid therapy, or treatment with other agents that interfere with hormonal measurements within one month of test session.
  • Subjects taking any psychotropic medications,antidepressants, opiates or opiate antagonists because these may affect test response. Subjects taking SSRI's will be included.
  • Subjects with any acute illness or fever. Individuals who otherwise meet study criteria will be rescheduled for evaluation for participation.
  • Subjects who are obese (BMI>35) as this may interfere with hormonal status.
  • Subjects who are unwilling or unable to maintain abstinence from alcohol and other drugs of abuse (except nicotine) for three days prior to the stress task procedure.
  • Subjects meeting DSM-IV criteria for substance dependence (other than nicotine, alcohol, marijuana or cocaine as appropriate) within the past 60 days.

Sites / Locations

  • Medical University of South Carolina-GCRC

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Other

Other

Other

Other

Other

Other

Other

Other

Arm Label

Cocaine Females, Yohimbine then Placebo

Cocaine Females, Placebo the Yohimbine

Cocaine Males, Yohimbine then Placebo

Cocaine Males, Placebo thenYohimbine

Control Females, Yohimbine then Placebo

Control Females, Placebo then Yohimbine

Control Males, Yohimbine then Placebo

Control Males, Placebo then Yohimbine

Arm Description

Cocaine dependent females, received yohimbine day 1 and placebo day 2

Cocaine dependent females, received placebo day 1 and yohimbine day 2

Cocaine dependent males, received yohimbine day 1 and placebo day 2

Cocaine dependent males, received placebo day 1 and yohimbine day 2

Non-dependent females, received yohimbine day 1 and placebo day 2

Non-dependent females, received placebo day 1 and yohimbine day 2

Non-dependent males, received yohimbine day 1 and placebo day 2

Non-dependent males, received placebo day 1 and yohimbine day 2

Outcomes

Primary Outcome Measures

Cocaine Craving
Cocaine-dependent participants were pre-treated with either yohimbine or placebo provided subjective ratings of cocaine craving immediately following cocaine cue exposure. The scale used was the Within Sessions Ratings Scales (Childress AR, McLellan AT, O'Brien CP (1986) Conditioned responses in a methadone population. A comparison of laboratory, clinic, and natural settings. Journal of Substance Abuse Treatment 3:173-179.) Craving was rated on a scale of 0-10 with 0 being Not At All and 10 being Extremely.

Secondary Outcome Measures

Full Information

First Posted
September 21, 2007
Last Updated
May 4, 2017
Sponsor
Medical University of South Carolina
Collaborators
National Institute on Drug Abuse (NIDA), Office of Research on Women's Health (ORWH)
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1. Study Identification

Unique Protocol Identification Number
NCT00535002
Brief Title
The Effect of Yohimbine on Cocaine Cue Reactivity
Official Title
SCOR on Sex and Gender Factors Affecting Women's Health
Study Type
Interventional

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
September 2007 (undefined)
Primary Completion Date
August 2012 (Actual)
Study Completion Date
August 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medical University of South Carolina
Collaborators
National Institute on Drug Abuse (NIDA), Office of Research on Women's Health (ORWH)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Stress and cues reminiscent of cocaine use promote craving and relapse in cocaine dependent individuals. In addition, there appears to be gender differences in determinants of relapse to drug use following abstinence in cocaine-dependent individuals. Therefore the purpose of the present study is to study the role of hormonal status on the response to cocaine-related cues with or without stress in cocaine-dependent women and men.
Detailed Description
Cocaine dependence is an insidious disease underscored by a strong propensity to relapse despite knowledge of the repercussions of continued drug-use. Stress and cocaine cues produce craving and ultimately relapse in cocaine dependent individuals. Pre-clinical research has demonstrated sex differences in response to cocaine-conditioned cues and cocaine-primed reinstatement, which correlates well with reduced plasma progesterone levels. Interestingly, this is consistent with a growing body of clinical literature indicating that progesterone may decrease the reinforcing properties of stimulants in women. Gender differences in the response to a social stressor and cocaine cues in cocaine-dependent individuals have been demonstrated in human laboratory studies, however, the interaction of stress and cues and the effect of hormonal status on response have not been explored. This study examines the role of hormonal status on the response to cocaine-related cues with or without a pharmacological stressor (yohimbine) in cocaine-dependent women and men. As a further integration of the research focus this study also explores the relationship between impulsivity and craving.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cocaine Related Disorders
Keywords
Cocaine Addiction, Cocaine Dependence

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
112 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cocaine Females, Yohimbine then Placebo
Arm Type
Other
Arm Description
Cocaine dependent females, received yohimbine day 1 and placebo day 2
Arm Title
Cocaine Females, Placebo the Yohimbine
Arm Type
Other
Arm Description
Cocaine dependent females, received placebo day 1 and yohimbine day 2
Arm Title
Cocaine Males, Yohimbine then Placebo
Arm Type
Other
Arm Description
Cocaine dependent males, received yohimbine day 1 and placebo day 2
Arm Title
Cocaine Males, Placebo thenYohimbine
Arm Type
Other
Arm Description
Cocaine dependent males, received placebo day 1 and yohimbine day 2
Arm Title
Control Females, Yohimbine then Placebo
Arm Type
Other
Arm Description
Non-dependent females, received yohimbine day 1 and placebo day 2
Arm Title
Control Females, Placebo then Yohimbine
Arm Type
Other
Arm Description
Non-dependent females, received placebo day 1 and yohimbine day 2
Arm Title
Control Males, Yohimbine then Placebo
Arm Type
Other
Arm Description
Non-dependent males, received yohimbine day 1 and placebo day 2
Arm Title
Control Males, Placebo then Yohimbine
Arm Type
Other
Arm Description
Non-dependent males, received placebo day 1 and yohimbine day 2
Intervention Type
Drug
Intervention Name(s)
Yohimbine
Intervention Description
Participants were pre-treated with either yohimbine or placebo.
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Cocaine Craving
Description
Cocaine-dependent participants were pre-treated with either yohimbine or placebo provided subjective ratings of cocaine craving immediately following cocaine cue exposure. The scale used was the Within Sessions Ratings Scales (Childress AR, McLellan AT, O'Brien CP (1986) Conditioned responses in a methadone population. A comparison of laboratory, clinic, and natural settings. Journal of Substance Abuse Treatment 3:173-179.) Craving was rated on a scale of 0-10 with 0 being Not At All and 10 being Extremely.
Time Frame
Post cocaine cue exposure

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Subjects must be able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments. Subjects must consent to remain abstinent from all drugs of abuse (except nicotine) for a three-day period immediately prior to the CTRC admission. Nicotine dependence can affect HPA function (Baron et al., 1995) therefore it would be ideal to exclude subjects with nicotine use. Because of the high comorbidity of cocaine and nicotine dependence, this would seriously compromise the feasibility of recruitment. Individuals with alcohol dependence will be excluded. However because of the high comorbidity of alcohol use and cocaine dependence, individuals with alcohol abuse will be included. Also, due to the high comorbidity of cocaine and marijuana dependence, and limited evidence that marijuana use affects HPA function, subjects with marijuana dependence will be included. Subjects with ADHD will be included. Because ADHD is commonly characterized by impulsivity, ADHD severity ratings will be determined and controlled for in data analysis. Subjects must consent to random assignment. Subjects must consent to outpatient admission to the CTRC and two overnight admissions to the Medical University Hospital. Exclusion Criteria: Women who are pregnant, nursing or of childbearing potential and not practicing an effective means of birth control. Women with premenstrual dysphoric disorder as this may impact on the response to the stress test procedure (Woods et al., 1994). Women receiving depot medroxyprogesterone acetate as a form of birth control. Subjects with evidence of or a history of significant hematological, endocrine, cardiovascular, pulmonary, renal, gastrointestinal, or neurological disease including diabetes, as these conditions may affect physiological/subjective responses. Subjects with Addison's disease, Cushing's disease or other diseases of the adrenal cortex likely to affect hormonal/neuroendocrine status. Subjects with a history of or current psychotic disorder or bipolar affective disorder as these may interfere with subjective measurements. Subjects with current major depressive disorder or post-traumatic stress disorder as these disorders are associated with characteristic changes in stress response. Subjects with panic disorder, as yohimbine may precipitate panic attacks. Subjects receiving synthetic glucocorticoid therapy, any exogenous steroid therapy, or treatment with other agents that interfere with hormonal measurements within one month of test session. Subjects taking any psychotropic medications,antidepressants, opiates or opiate antagonists because these may affect test response. Subjects taking SSRI's will be included. Subjects with any acute illness or fever. Individuals who otherwise meet study criteria will be rescheduled for evaluation for participation. Subjects who are obese (BMI>35) as this may interfere with hormonal status. Subjects who are unwilling or unable to maintain abstinence from alcohol and other drugs of abuse (except nicotine) for three days prior to the stress task procedure. Subjects meeting DSM-IV criteria for substance dependence (other than nicotine, alcohol, marijuana or cocaine as appropriate) within the past 60 days.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kathleen T Brady, M.D., Ph.D.
Organizational Affiliation
Medical University of South Carolina
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical University of South Carolina-GCRC
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States

12. IPD Sharing Statement

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The Effect of Yohimbine on Cocaine Cue Reactivity

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