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Effect of Clonidine on Responses to Imagery Scripts

Primary Purpose

Cocaine Abuse, Heroin Abuse

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Clonidine
Placebo
Sponsored by
National Institute on Drug Abuse (NIDA)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cocaine Abuse focused on measuring Drug Cue, Relapse, Stress, Craving

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

INCLUSION CRITERIA: Age between 18 and 55; Evidence of current cocaine and/or heroin use (by self-report) with a minimum lifetime drug-use duration of 1 year and a minimum current drug use of once in the last 30 days; EXCLUSION CRITERIA: Hypersensitivity to clonidine or any component of the formulation Schizophrenia or any other DSM-IV psychotic disorder; history of anxiety disorder, panic disorder, bipolar disorder; current Major Depressive Disorder Current physical dependence on opioids, cocaine, alcohol, benzodiazepines or other sedative-hypnotic; this is an exclusion criterion because we want to evaluate the ability of clonidine to affect stress- and cue-induced drug craving independent of its effects on drug withdrawal Cognitive impairment severe enough to preclude informed consent or valid responses on questionnaires Pregnancy or breast feeding Severely impaired hepatic function Severely impaired renal function, with CLcr < 10 ml/minute Medical conditions that contraindicate or that could complicate clonidine administration: hypotension (SBP <95 or DBP < 40 mm Hg) over several readings hypertension(SBP >160 mm Hg, DBP >95 mm Hg) over several readings orthostatic hypotension over several readings or as a consequence of any underlying medical disorder (e.g., autonomic insufficiency) bradycardia (heart rate < 50 bpm) over several readings cerebrovascular disease or any history of CVA or transient ischemic attack (TIA) documented coronary disease serious arrhythmia or conduction defect (e.g., second or third degree heart block, atrial fibrillation) sinus node dysfunction, severe bradycardia or symptomatic bradycardia congestive heart failure Medications that could interact adversely with clonidine: antipsychotics; antihypertensives (e.g., beta blockers); antiepileptics; CNS depressants (e.g. barbiturates, benzodiazepines, narcotic analgesics, alcohol, or other sedatives); cyclosporine; oral hypoglycemic agents or insulin; levodopa; tricyclic antidepressants; herbals such as dong quai, ephedra, yohimbe, ginseng, valerian, St. John s wort, kava kava, gotu kola Women who are able to get pregnant and are not abstinent from sexual activity must agree to use a medically effective form of contraception while in the study. Those include: Hormonal contraceptives (birth control pills, injectable hormones, vaginal ring hormones), Surgical sterility (tubal ligation or hysterectomy) IUD Diaphragm with spermicide Condom with spermicide Women who do not agree to use these medically effective forms of contraception while in the study will be excluded.

Sites / Locations

  • National Institute on Drug Abuse

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

ARM 1

ARM 2

Arm Description

Outcomes

Primary Outcome Measures

Subjective ratings of drug craving and mood
Autonomic response (galvanic skin response [GSR])
Heart rate and blood pressure
Endocrine responses (salivary cortisol and salivary alpha-amylase)

Secondary Outcome Measures

Full Information

First Posted
April 25, 2006
Last Updated
April 4, 2018
Sponsor
National Institute on Drug Abuse (NIDA)
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1. Study Identification

Unique Protocol Identification Number
NCT00318760
Brief Title
Effect of Clonidine on Responses to Imagery Scripts
Official Title
Effect of Clonidine on Responses to Imagery Scripts
Study Type
Interventional

2. Study Status

Record Verification Date
July 8, 2014
Overall Recruitment Status
Completed
Study Start Date
June 14, 2005 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
August 7, 2013 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
National Institute on Drug Abuse (NIDA)

4. Oversight

5. Study Description

Brief Summary
Background: - Research has shown that clonidine, a drug originally prescribed to treat high blood pressure and some symptoms of opioid withdrawal, can help block stress-induced relapse to heroin and cocaine seeking in rats. However, it does not seem to block cue-induced relapse in rats. Researchers are interested in studying whether clonidine shows the same pattern of effects on stress- and cue-induced cravings for heroin or cocaine in humans. Objectives: - To compare the ability of clonidine to reduce stress- and cue-induced cocaine and heroin craving in drug abusers. Eligibility: - Individuals between 18 and 55 years of age who are current cocaine or heroin users. Design: This study will consist of two visits: a screening visit to determine eligibility and an experimental/script session. Before the script session, participants will provide urine and breath samples for testing. Participants will complete questionnaires to measure their current drug craving and days since last use of cocaine or heroin. At the start of the script session, participants will receive a dose of clonidine or placebo as directed by the study researchers. Three hours after dosing, participants will be read four scripts (two neutral, one stress-inducing, and one drug-cue-related) with breaks in between each script. After each script, participants will respond to questions about levels of stress and craving. Participants will provide saliva samples immediately before and during the script readings, and will also be measured for skin response to the scripts.
Detailed Description
Background. Stress and exposure to drug-related cues (environmental stimuli previously associated with drug availability) are considered factors that increase the risk of relapse to heroin and/or cocaine use. The two factors may act through different neural mechanisms. Alpha-2 adrenergic agonists, such as clonidine, have been shown to block stress-induced relapse, but not cue-induced relapse, to heroin and cocaine self-administration in rodents. The ability of clonidine to attenuate stress- or cue-induced heroin and cocaine craving in drug abusers has not been tested. It is important to determine, in humans, whether clonidine blocks the acute effects of only one putative class of relapse precipitants, or whether its effects are more general. Scientific goal. To compare the ability of clonidine to reduce stress-induced and cue-induced cocaine and heroin craving in drug abusers. Participant population. A total of up to 160 drug abusers using cocaine, heroin, or both will be enrolled. Target enrollment will include 40% women and 60% minorities (mostly African-American). Experimental design and methods. Participants will be randomized to one of three groups receiving clonidine 0.1 mg, clonidine 0.2 mg, or placebo orally under double-blind conditions. The study will consist of a single 5-6 hr experimental session in which there will be baseline measures, drug administration, and four script-guided imagery sets, each followed by a period of data collection. Three hours after dosing (when peak plasma clonidine concentrations are reached), participants will be exposed to four scripts: one stress-inducing, one describing drug cues, and two with neutral content. The standardized script-guided imagery procedure has previously been shown to reliably induce negative affective states (stress scripts) and/or craving (stress and drug-cue scripts) compared to the neutral scripts and to have internal and external validity (Tiffany and Drobes, 1990; Maude-Griffin and Tiffany, 1996; Taylor et al., 2000; Sinha et al., 1999, 2000, 2003; Singleton et al., 2003; Tiffany and Haekeneworth, 1991; Elash et al., 1995; Drobes and Tiffany, 1997; Taylor et al., 2000; Singleton et al., 2003). Outcome measures will include subjective ratings of drug craving and mood, autonomic response (galvanic skin response [GSR]), and endocrine responses (salivary cortisol and salivary ?-amylase, a measure of endogenous adrenergic activity during stress (Chatterton et al., 1996; Nater et al., 2005; van Stegeren et al., 2005)). Benefits to participants and/or society. There are no direct benefits to participants. However, if clonidine is effective in blocking stress-induced and/or cue-induced craving, then the results will be used as a basis for designing a treatment trial, and drug abusers and society may benefit from the eventual use of clonidine or other alpha agonists for prevention of relapse in cocaine and heroin users. In addition, this research will provide information on the clinical relevance of a preclinical model of relapse, possibly strengthening arguments for its use in medication development. Risks to participants. Participants may experience side effects from clonidine such as sedation and are expected to experience brief, mild psychological stress and drug craving from the laboratory script procedures. Prior to leaving the session, participants will be assessed for the presence of continued drug effects. If participants are experiencing any stress or craving at the end of the session, they will undergo a 10-minute guided relaxation session, which will be repeated until feelings of stress or craving dissipate, before being released from the laboratory. Participants may be kept longer than the planned session length, up to and including staying overnight on the inpatient ward, because of continued side effects or elevated stress or craving. If the MRP deems it medically necessary, participants will be sent to JHBMC emergency department for further evaluation and treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cocaine Abuse, Heroin Abuse
Keywords
Drug Cue, Relapse, Stress, Craving

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Allocation
Randomized
Enrollment
92 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ARM 1
Arm Type
Experimental
Arm Title
ARM 2
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Clonidine
Intervention Description
0.1 or 0.2 mg oral, one dose
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
oral capsule 1 dose
Primary Outcome Measure Information:
Title
Subjective ratings of drug craving and mood
Time Frame
1 hr
Title
Autonomic response (galvanic skin response [GSR])
Time Frame
1 hr
Title
Heart rate and blood pressure
Time Frame
1 hr
Title
Endocrine responses (salivary cortisol and salivary alpha-amylase)
Time Frame
1 hr

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA: Age between 18 and 55; Evidence of current cocaine and/or heroin use (by self-report) with a minimum lifetime drug-use duration of 1 year and a minimum current drug use of once in the last 30 days; EXCLUSION CRITERIA: Hypersensitivity to clonidine or any component of the formulation Schizophrenia or any other DSM-IV psychotic disorder; history of anxiety disorder, panic disorder, bipolar disorder; current Major Depressive Disorder Current physical dependence on opioids, cocaine, alcohol, benzodiazepines or other sedative-hypnotic; this is an exclusion criterion because we want to evaluate the ability of clonidine to affect stress- and cue-induced drug craving independent of its effects on drug withdrawal Cognitive impairment severe enough to preclude informed consent or valid responses on questionnaires Pregnancy or breast feeding Severely impaired hepatic function Severely impaired renal function, with CLcr < 10 ml/minute Medical conditions that contraindicate or that could complicate clonidine administration: hypotension (SBP <95 or DBP < 40 mm Hg) over several readings hypertension(SBP >160 mm Hg, DBP >95 mm Hg) over several readings orthostatic hypotension over several readings or as a consequence of any underlying medical disorder (e.g., autonomic insufficiency) bradycardia (heart rate < 50 bpm) over several readings cerebrovascular disease or any history of CVA or transient ischemic attack (TIA) documented coronary disease serious arrhythmia or conduction defect (e.g., second or third degree heart block, atrial fibrillation) sinus node dysfunction, severe bradycardia or symptomatic bradycardia congestive heart failure Medications that could interact adversely with clonidine: antipsychotics; antihypertensives (e.g., beta blockers); antiepileptics; CNS depressants (e.g. barbiturates, benzodiazepines, narcotic analgesics, alcohol, or other sedatives); cyclosporine; oral hypoglycemic agents or insulin; levodopa; tricyclic antidepressants; herbals such as dong quai, ephedra, yohimbe, ginseng, valerian, St. John s wort, kava kava, gotu kola Women who are able to get pregnant and are not abstinent from sexual activity must agree to use a medically effective form of contraception while in the study. Those include: Hormonal contraceptives (birth control pills, injectable hormones, vaginal ring hormones), Surgical sterility (tubal ligation or hysterectomy) IUD Diaphragm with spermicide Condom with spermicide Women who do not agree to use these medically effective forms of contraception while in the study will be excluded.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kenzie Preston, Ph.D.
Organizational Affiliation
National Institute on Drug Abuse (NIDA)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institute on Drug Abuse
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
9097890
Citation
Abduljawad KA, Langley RW, Bradshaw CM, Szabadi E. Effects of clonidine and diazepam on the acoustic startle response and on its inhibition by 'prepulses' in man. J Psychopharmacol. 1997;11(1):29-34. doi: 10.1177/026988119701100110.
Results Reference
background
PubMed Identifier
8647351
Citation
Benschop RJ, Jacobs R, Sommer B, Schurmeyer TH, Raab JR, Schmidt RE, Schedlowski M. Modulation of the immunologic response to acute stress in humans by beta-blockade or benzodiazepines. FASEB J. 1996 Mar;10(4):517-24. doi: 10.1096/fasebj.10.4.8647351.
Results Reference
background
PubMed Identifier
8596268
Citation
Berger SP, Hall S, Mickalian JD, Reid MS, Crawford CA, Delucchi K, Carr K, Hall S. Haloperidol antagonism of cue-elicited cocaine craving. Lancet. 1996 Feb 24;347(9000):504-8. doi: 10.1016/s0140-6736(96)91139-3.
Results Reference
background

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Effect of Clonidine on Responses to Imagery Scripts

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