Human Behavioral Pharmacology Laboratory (HBPL) Study of Varenicline's Impact on Cocaine and Alcohol Craving

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT01151813
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 15
• Location: 1
• Arms: 2
• Duration (Months): 41
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This is a Phase II within-subjects double-blind placebo-controlled human laboratory study. The purpose of the study is to determine the efficacy of varenicline (Chantix) for reducing cue-induced cocaine and alcohol craving.

Condition or Disease	Intervention/Treatment	Phase
Alcohol Dependence; Cocaine Dependence	Drug: Varenicline; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Study Start Date: Jul 1, 2010
• Actual Primary Completion Date: Aug 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Varenicline Varenicline, oral administration for 1 week	Drug: Varenicline; Varenicline, oral target dose of 1.0 mg BID, one week titration.; Other Names: Chantix
Placebo Comparator: Placebo Placebo, oral administration for 1 week	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Visual Analog Scale Alcohol Craving [average value over one week]

   Visual Analog Scale specific to alcohol craving. The VAS has a 100 mm line anchored by 0 and 100. Participants mark the line to indicate how strong their craving is for alcohol. 0 indicates no craving 100 indicates strongest possible craving.

2. Visual Analog Scale Cocaine Craving [average value over one week]

   Visual Analog Scale specific to cocaine craving. The VAS has a 100 mm line anchored by 0 and 100. Participants mark the line to indicate how strong their craving is for cocaine. 0 indicated no craving, 100 represents the worst craving imaginable. The subject draws a hatch mark line along the line closer to where there current craving is rated.

3. Visual Analog Scale Alcohol Craving 2 [average over one week]

   Visual Analog Scale specific to alcohol craving. The VAS has a 100 mm line anchored by 0 and 100. Participants mark the line to indicate how strong their craving is for alcohol. 0 indicated no craving, 100 represents the worst craving imaginable. The subject draws a hatch mark line along the line closer to where there current craving is rated. Closer to the 0 means less craving, closer to the 100 means more craving

4. Visual Analog Scale Cocaine Craving 2 [average over one week]

   Visual Analog Scale specific to cocaine craving. The VAS has a 100 mm line anchored by 0 and 100. Participants mark the line to indicate how strong their craving is for cocaine. 0 indicated no craving, 100 represents the worst craving imaginable. The subject draws a hatch mark line along the line closer to where there current craving is rated. Closer to the 0 means less craving, closer to the 100 means more craving

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subject is male or female and is between 21 and 65 years of age.

2. The subject has used cocaine, alcohol, or cocaine and alcohol at least once per month for at least the past year, and has used cocaine, alcohol, or cocaine and alcohol within the past 30 days.

3. Live within a commutable distance of the Treatment Research Center (TRC) at the Penn/VA Center for Studies of Addiction, University of Pennsylvania. We define this to be a distance within the service area of Septa, within an hour drive, or a distance that both the patient and Principal Investigator (PI) find acceptable.

4. Understands and signs the informed consent.

Exclusion Criteria:

1. Meets DSM-IV criteria for current dependence on any substance other than nicotine, cocaine, alcohol or marijuana.

2. Subjects who are currently taking anti-depressant medications (e.g., SSRIs such as citalopram)

3. Patients who are diagnosed during screening with clinical depression using the HAM-D rating scale and present with a score >10.

4. Subjects who are diagnosed with anxiety as diagnosed using the HAM-A anxiety scale with a score >17

5. Subjects who meet current- or lifetime DSM-IV criteria for a psychotic disorder (e.g., schizophrenia)

6. Requires treatment with any psychotropic medication (e.g., antidepressant, antipsychotic, benzodiazepine, or mood stabilizing medication).

7. Subjects who test positive on the urine drug screen for any illicit drugs other than cocaine and marijuana during screening will be allowed a single retest. Those individuals who test positive for amphetamine during screening, given that they provide a copy of a prescription, will only be included if they can safely discontinue amphetamine use for the duration of the study. Subjects will need to provide a urine free of all illicit drugs other than cocaine and marijuana at study onset to be randomized. Subjects who test positive for any drugs other than marijuana prior to a study session will be allowed a single retest and a chance to reschedule their session. If the subject tests positive for any drug other than marijuana at the retest, their participation in the study will be terminated.

8. Use of any investigational medication within the past 30 days.

9. Concomitant use of any one of the following drugs or classes of drugs:

Anti-depressant drugs such as citalopram, fluoxetine; antipsychotic drugs such as haloperidol; benzodiazepines or other anxiolytic medications; Antihypertensive drugs such as Reserpine, Verapamil; Blood thinners Medications used to treat respiratory diseases such as theophylline; Trimethoprim; Cimetidine; Antiepileptic drugs (AEDs) such as phenytoin or valproic acid.

1. Patients with a known hypersensitivity to varenicline.

2. Patients with severe unstable or serious medical illness such as a seizure disorder, unstable cerebrovascular disease, bronchospastic disease, hyperthyroidism, or diabetes mellitus.

3. Patients with known AIDS or other serious illnesses that may require hospitalization during the study.

4. Female subjects who are pregnant, plan to become pregnant, are currently lactating, or are of child-bearing potential and are not using acceptable methods of birth control; acceptable methods of birth control would include:

5. Barrier method (diaphragm or condom)

6. Intrauterine progesterone contraceptive system

7. Levonorgesterel implant

8. Medroxyprogesterone acetate contraceptive injection, or

9. Oral contraceptives.

10. Patients with impaired renal function, as indicated by corrected creatinine clearance below 60 ml/min as determined by the modified Cockcroft equation (CDC, 1986).

11. An unacceptable liver panel (liver function tests; LFTs) that may be indicative of hepatic dysfunction.

12. Clinical laboratory tests (e.g., CBC, blood chemistries, urinalysis) outside normal limits, as determined by PI.

13. History of significant heart disease or dysfunction (e.g., an arrhythmia which required medication, Wolff Parkinson -White Syndrome, angina pectoris, documented history of myocardial infarction, heart failure).

14. Electrocardiography (EKG) indicative of 1st degree heart block, sinus tachycardia, left-axis deviation, non-specific ST or T-wave changes.

15. History of chest pain associated with cocaine use that prompted a visit to a physician.

16. Any medical or psychological condition that could jeopardize the subject's safe participation in the trial as determined by the PI.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pennsylvania, Treatment Research Center	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• University of Pennsylvania
• National Institute on Drug Abuse (NIDA)

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT01151813
• Other Study ID Numbers: 811289; K01DA025073
• First Posted: Jun 28, 2010
• Last Update Posted: Aug 18, 2020
• Last Verified: Aug 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Alcoholism; Cocaine-Related Disorders; Varenicline

Study Results

Participant Flow

Arm/Group Title	Varenicline First, Then Placebo	Placebo First, Then Varenicline
Arm/Group Description	Varenicline, oral target dose of 1.0 mg BID, one week titration; followed by placebo, matched for one week.	Placebo for one week, followed by Varenicline, oral target dose of 1.0 mg BID, one week titration.
Period Title: Period 1
STARTED	8	7
COMPLETED	8	7
NOT COMPLETED	0	0
Period Title: Period 1
STARTED	8	7
COMPLETED	8	7
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Within-subjects Design
Arm/Group Description	Varenicline, oral target dose of 1.0 mg BID, one week titration; placebo, matched for one week. Double-blind counterbalanced order
Overall Participants	15
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	15 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	3 20%
Male	12 80%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 6.7%
Not Hispanic or Latino	14 93.3%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	12 80%
White	3 20%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	15 100%

Outcome Measures

1. Primary Outcome

Title	Visual Analog Scale Alcohol Craving
Description	Visual Analog Scale specific to alcohol craving. The VAS has a 100 mm line anchored by 0 and 100. Participants mark the line to indicate how strong their craving is for alcohol. 0 indicates no craving 100 indicates strongest possible craving.
Time Frame	average value over one week

Outcome Measure Data

Analysis Population Description

Comparing alcohol craving during Varenicline treatment in participants initially treated with Varenicline (Group 1) to those initially treated with Placebo (Group 2).

Arm/Group Title	Varenicline First, Then Placebo	Placebo First, Then Varenicline
Arm/Group Description	Varenicline, oral target dose of 1.0 mg BID, one week titration; followed by placebo, matched for one week.	Placebo for one week; followed by Varenicline, oral target dose of 1.0 mg BID, one week titration.
Measure Participants	8	7
Mean (Full Range) [units on a scale]	20	35

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Varenicline First, Then Placebo, Placebo First, Then Varenicline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	.02
	Comments
	Method	t-test, 2 sided
	Comments

2. Primary Outcome

Title	Visual Analog Scale Cocaine Craving
Description	Visual Analog Scale specific to cocaine craving. The VAS has a 100 mm line anchored by 0 and 100. Participants mark the line to indicate how strong their craving is for cocaine. 0 indicated no craving, 100 represents the worst craving imaginable. The subject draws a hatch mark line along the line closer to where there current craving is rated.
Time Frame	average value over one week

Outcome Measure Data

Analysis Population Description

Comparing cocaine craving during Varenicline treatment in participants initially treated with Varenicline (Group 1) to those initially treated with Placebo (Group 2).

Arm/Group Title	Varenicline First, Then Placebo	Placebo First, Then Varenicline
Arm/Group Description	Varenicline, oral target dose of 1.0 mg BID, one week titration; placebo, matched for one week.	Placebo for one week; followed by Varenicline, oral target dose of 1.0 mg BID, one week titration.
Measure Participants	8	7
Mean (Full Range) [units on a scale]	25	65

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Varenicline First, Then Placebo, Placebo First, Then Varenicline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	t-test, 2 sided
	Comments

3. Primary Outcome

Title	Visual Analog Scale Alcohol Craving 2
Description	Visual Analog Scale specific to alcohol craving. The VAS has a 100 mm line anchored by 0 and 100. Participants mark the line to indicate how strong their craving is for alcohol. 0 indicated no craving, 100 represents the worst craving imaginable. The subject draws a hatch mark line along the line closer to where there current craving is rated. Closer to the 0 means less craving, closer to the 100 means more craving
Time Frame	average over one week

Outcome Measure Data

Analysis Population Description

Comparing alcohol craving during Placebo treatment in participants initially treated with Varenicline (Group 1) to those initially treated with Placebo (Group 2).

Arm/Group Title	Varenicline First, Then Placebo	Placebo First, Then Varenicline
Arm/Group Description	Varenicline, oral target dose of 1.0 mg BID, one week titration; followed by placebo, matched for one week.	Placebo for one week; followed by Varenicline, oral target dose of 1.0 mg BID, one week titration.
Measure Participants	8	7
Mean (Full Range) [units on a scale]	35	55

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Varenicline First, Then Placebo, Placebo First, Then Varenicline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	t-test, 2 sided
	Comments

4. Primary Outcome

Title	Visual Analog Scale Cocaine Craving 2
Description	Visual Analog Scale specific to cocaine craving. The VAS has a 100 mm line anchored by 0 and 100. Participants mark the line to indicate how strong their craving is for cocaine. 0 indicated no craving, 100 represents the worst craving imaginable. The subject draws a hatch mark line along the line closer to where there current craving is rated. Closer to the 0 means less craving, closer to the 100 means more craving
Time Frame	average over one week

Outcome Measure Data

Analysis Population Description

Comparing cocaine craving during Placebo treatment in participants initially treated with Varenicline (Group 1) to those initially treated with Placebo (Group 2).

Arm/Group Title	Varenicline First, Then Placebo	Placebo First, Then Varenicline
Arm/Group Description	Varenicline, oral target dose of 1.0 mg BID, one week titration; placebo, matched for one week.	Placebo for one week; followed by Varenicline, oral target dose of 1.0 mg BID, one week titration.
Measure Participants	8	7
Mean (Full Range) [units on a scale]	65	80

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Varenicline First, Then Placebo, Placebo First, Then Varenicline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	through study completion, two weeks
Adverse Event Reporting Description	Participants were asked to report adverse events at each study visit by nurses using a checklist of known (previously reported) adverse events, as well as novel adverse events.
Arm/Group Title	Varenicline		Placebo
Arm/Group Description	While receiving Varenicline, oral target dose of 1.0 mg BID, one week titration		While receiving Placebo, one week
All Cause Mortality
	Varenicline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)
Serious Adverse Events
	Varenicline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Varenicline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/15 (20%)		1/15 (6.7%)
Gastrointestinal disorders
Flatulence	3/15 (20%)	3	1/15 (6.7%)	1

Limitations/Caveats

[Not Specified]

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.