Prazosin for ETOH or Cocaine Craving

• Sponsor: US Department of Veterans Affairs (U.S. Fed)
• Overall Status: Terminated
• CT.gov ID: NCT00240227
• Collaborator: (none)
• Enrollment: 8
• Location: 1
• Arms: 2
• Duration (Months): 57
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This double-blind placebo controlled crossover pilot trial will test the hypothesis that prazosin, an alpha-1 adrenergic receptor antagonist, reduces craving for their drug of choice in cocaine-dependent and alcohol-dependent veterans. Both the study medication period and the placebo period are each 4 weeks in duration.

Condition or Disease	Intervention/Treatment	Phase
Alcoholism; Cocaine Dependence	Drug: Prazosin; Drug: placebo	N/A

Detailed Description

1. Objective of the project: To evaluate the efficacy of prazosin on the reduction of craving in alcohol and cocaine dependent individuals. The investigators hypothesize that prazosin will be more effective than placebo in the reduction of craving that is stimulated by exposure to visual cues or to intolerance to stress in individuals dependent on cocaine and in individuals dependent on alcohol.

Specifically, the investigators hypothesize that in this laboratory study:

• Subjects in the prazosin condition will report a reduction in craving induced in the laboratory by exposure to visual cues compared to subjects in the placebo condition.

• Subjects in the prazosin condition will show less reaction of the noradrenergic system when craving is induced in the laboratory by exposure to visual cues compared to subjects in the placebo condition.

• Subjects will be less likely to relapse to their drug of choice while they are in the prazosin condition compared to when they are in the placebo condition. Most individuals who are able to achieve sobriety in chemical dependency treatment eventually relapse. Until the investigators can prevent the cravings for drugs, which usually precedes relapse, it is unlikely that the investigators will have more effective treatment for drug addiction. Our final hypothesis is that the alpha-1, adrenergic antagonist, prazosin, will prove to be an effective pharmacological agent for treatment of drug dependency.

1. Research plan study design: The proposed study will be a double-blind, placebo-controlled, crossover study of prazosin in subjects who are either dependent on alcohol or on cocaine, and who have been able to achieve one month of sobriety while in intensive outpatient treatment. The double-blind, crossover protocol will last 8 weeks and will include 32 subjects; 16 of whom are alcohol-dependent, and 16 of whom are cocaine-dependent. The focus of this first study will be on subjective and physiological measures of craving that will be induced in a controlled setting by exposure to visual cues.

2. Methodology Setting: This study will occur in room 6A-107 in Building 1 at the Veterans Administration Puget Sound Health Care System in Seattle. This is a soundproof room specifically designed and constructed for studies of this type. Participants: 16 alcohol-dependent adults and 16 cocaine-dependent adults presenting for chemical dependency treatment at the VA Puget Sound Health Care System (VAPSHCS) Addiction Treatment Center. Study Procedures: Once potential subjects have provided their consent to participate in the study, they will undergo a 2 hour baseline assessment that consists of some pencil and paper questionnaires, providing a medical and psychiatric history, and a physical exam. They will provide blood for some basic screening labs to insure they are healthy enough to proceed with the study, and have their baseline vital signs measured. Veterans who are screened for the study will then be enrolled once their lab results and the screening process have determined that they do not meet any medical exclusion criteria. At that point, participants will be randomized to either the study medication or placebo. During the course of the study, participants continue with their outpatient chemical dependency treatment through the Addiction Treatment Center at the VA Puget Sound. During the eight weeks of the study, participants will have weekly orthostatic vital sign and adverse events monitoring by the study nurse or physician. All serious or unexpected adverse events will be reported to the FDA and UW Human Subjects Committee in accordance with requirements. Participants will also provide self-reports of drug or alcohol use and urine drug analysis specimens at these weekly visits. At the end of week 4, each participant will be tested in a 1 hour craving session in room 6A-107 at VA Puget Sound. Subjects will have their heart rate and skin conductance response continuously measured, and have their blood pressure measured every 5 minutes. They will be shown 5 1-minute films, 3 of which are designed to be neutral and 2 of which are designed to provoke craving for their drug of choice. They will be asked to complete a subjective scale of craving prior to each video and after the last video. Participants will not be permitted to leave the craving lab after the last film, until they feel that they have subjectively returned to a level of normal physiological arousal and are no longer experiencing any craving.

3. Findings: No findings to date.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Role of the Alpha 1-adrenergic Antagonist, Prazosin, in the Reduction of Craving and Relapse in Alcohol and Cocaine-dependent Individuals: a Double-blind, Randomized, Controlled Clinical Trial
• Study Start Date: Apr 1, 2004
• Actual Primary Completion Date: Jan 1, 2009
• Actual Study Completion Date: Jan 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Other: Placebo Placebo no active medication	Drug: placebo
Active Comparator: prazosin Prazosin flexible dose titration up to 12 mg per day.	Drug: Prazosin; FDA approved medication for hypertension; Other Names: Mini Press

Outcome Measures

Primary Outcome Measures

1. Change in Skin Conductance Response in Response to Provocative Visual Cues Designed to Elicit Craving, Compared to Placebo Group [During lab session]

Secondary Outcome Measures

1. Change in Heart Rate Response in Response to Provocative Visual Cues Designed to Elicit Craving, Compared to Placebo Group [During lab session]

2. Change in Blood Pressure Response in Response to Provocative Visual Cues Designed to Elicit Craving, Compared to Placebo Group [During lab session]

3. Change in Subjective Experience of Craving in Response to Provocative Visual Cues Designed to Elicit Craving, as Measured by the Within Session Rating for Cocaine/Alcohol Craving [During lab session]

4. Change in Self-reports of Substance Use Between Study Medication and Placebo Periods [4 weeks]

5. Change in Urine Drug Analysis Results Between Study Medication and Placebo Periods [4 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 18-70 years

• Current DSM-IV diagnosis of alcohol dependence or cocaine dependence with no use in last 30 days

• Capacity to provide informed consent

• Actively enrolled in chemical dependency treatment at VA Puget Sound English fluency

Exclusion Criteria:

• Evidence of significant abuse of opiates, PCP, sedatives or anxiolytics

• Suicidal ideation

• DSM IV diagnosis of bipolar mood disorder, schizophrenia or schizoaffective disorder

• Significant acute or chronic medical illness, including unstable angina, recent myocardial infarction, history of congestive heart failure, preexisting hypotension (systolic < 110), or orthostatic hypotension (systolic drop > 20mmHg after two minutes standing or any drop with dizziness), insulin-dependent diabetes mellitus; chronic renal or hepatic failure, pancreatitis, gout, M ni re's disease, benign positional vertigo, narcolepsy

• Concomitant use of alpha-1 antagonists History of prazosin-sensitivity Women who are pregnant, nursing infant(s), or of childbearing potential and not using a contraceptive method judged by the investigator to be effective

• Non-compliance with outpatient chemical dependency treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Puget Sound Health Care System	Seattle	Washington	United States	98109

Sponsors and Collaborators

• US Department of Veterans Affairs

Investigators

• Principal Investigator: Andrew J. Saxon, MD, VA Puget Sound Health Care System

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: US Department of Veterans Affairs
• ClinicalTrials.gov Identifier: NCT00240227
• Other Study ID Numbers: REAP 05-0020
• First Posted: Oct 17, 2005
• Last Update Posted: Aug 31, 2018
• Last Verified: Aug 1, 2018

• Keywords provided by US Department of Veterans Affairs: Alcoholism; Cocaine Dependence; Prazosin; Substance use disorders
• Additional relevant MeSH terms: Alcoholism; Cocaine-Related Disorders; Prazosin

Study Results

Participant Flow

Pre-assignment Detail	Participants were randomized to one of two sequences, either placebo first or prazosin first. However, the precise numbers of which sequence participants were randomized to are no longer available considering the time (7 years) since the study was completed.

Arm/Group Title	All Study Participants
Arm/Group Description	No active medication Prazosin flexible dose titration up to 12 mg per day. Prazosin: FDA approved medication for hypertension
Period Title: Overall Study
STARTED	8
COMPLETED	8
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	All Study Paricipants
Arm/Group Description	No active medication Prazosin FDA approved medication for hypertension
Overall Participants	8
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	8 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42 (8)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	8 100%
Region of Enrollment (participants) [Number]
United States	8 100%

Outcome Measures

1. Primary Outcome

Title	Change in Skin Conductance Response in Response to Provocative Visual Cues Designed to Elicit Craving, Compared to Placebo Group
Time Frame	During lab session

Outcome Measure Data

Analysis Population Description

Study was terminated early. No final analyses completed.

Arm/Group Title	Placebo	Prazosin
Arm/Group Description	No active medication	Prazosin flexible dose titration up to 12 mg per day. Prazosin: FDA approved medication for hypertension
Measure Participants	0	0

2. Secondary Outcome

Title	Change in Heart Rate Response in Response to Provocative Visual Cues Designed to Elicit Craving, Compared to Placebo Group
Time Frame	During lab session

Outcome Measure Data

Analysis Population Description

Study was terminated early. No final analyses completed.

Arm/Group Title	Placebo	Prazosin
Arm/Group Description	No active medication
Measure Participants	0	0

3. Secondary Outcome

Title	Change in Blood Pressure Response in Response to Provocative Visual Cues Designed to Elicit Craving, Compared to Placebo Group
Time Frame	During lab session

Outcome Measure Data

Analysis Population Description

Study was terminated early. No final analyses completed.

Arm/Group Title	Placebo	Prazosin
Arm/Group Description	No active medication	Prazosin flexible dose titration up to 12 mg per day. Prazosin: FDA approved medication for hypertension
Measure Participants	0	0

4. Secondary Outcome

Title	Change in Subjective Experience of Craving in Response to Provocative Visual Cues Designed to Elicit Craving, as Measured by the Within Session Rating for Cocaine/Alcohol Craving
Time Frame	During lab session

Outcome Measure Data

Analysis Population Description

Study was terminated early. No final analyses completed.

Arm/Group Title	Placebo	Prazosin
Arm/Group Description	No active medication	Prazosin flexible dose titration up to 12 mg per day. Prazosin: FDA approved medication for hypertension
Measure Participants	0	0

5. Secondary Outcome

Title	Change in Self-reports of Substance Use Between Study Medication and Placebo Periods
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Study was terminated early. No final analyses completed.

Arm/Group Title	Placebo	Prazosin
Arm/Group Description	No active medication	Prazosin flexible dose titration up to 12 mg per day. Prazosin: FDA approved medication for hypertension
Measure Participants	0	0

6. Secondary Outcome

Title	Change in Urine Drug Analysis Results Between Study Medication and Placebo Periods
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Study was terminated early. No final analyses completed.

Arm/Group Title	Placebo	Prazosin
Arm/Group Description	No active medication	Prazosin flexible dose titration up to 12 mg per day. Prazosin: FDA approved medication for hypertension
Measure Participants	0	0

Adverse Events

Arm/Group Title	Placebo		Prazosin
Arm/Group Description	Placebo no active medication placebo		Prazosin flexible dose titration up to 12 mg per day. Prazosin: FDA approved medication for hypertension
All Cause Mortality
	Placebo		Prazosin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Prazosin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Prazosin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		1/8 (12.5%)
Nervous system disorders
dizziness	0/8 (0%)	0	1/8 (12.5%)	1

Limitations/Caveats

The study procedure intended to induce substance craving failed to induce craving. Thus, any difference between placebo and active medication conditions could not be measured and so the study was terminated.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.