Alcohol Dependence, Cocaine Dependence
Conditions
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.
Interventions
DRUGVarenicline
Varenicline, oral target dose of 1.0 mg BID, one week titration.
DRUGPlacebo
Placebo
Sponsors
National Institute on Drug Abuse (NIDA)
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
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. 10. Patients with a known hypersensitivity to varenicline. 11. Patients with severe unstable or serious medical illness such as a seizure disorder, unstable cerebrovascular disease, bronchospastic disease, hyperthyroidism, or diabetes mellitus. 12. Patients with known AIDS or other serious illnesses that may require hospitalization during the study. 13. 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: 1. Barrier method (diaphragm or condom) 2. Intrauterine progesterone contraceptive system 3. Levonorgesterel implant 4. Medroxyprogesterone acetate contraceptive injection, or 5. Oral contraceptives. 14. Patients with impaired renal function, as indicated by corrected creatinine clearance below 60 ml/min as determined by the modified Cockcroft equation (CDC, 1986). 15. An unacceptable liver panel (liver function tests; LFTs) that may be indicative of hepatic dysfunction. 16. Clinical laboratory tests (e.g., CBC, blood chemistries, urinalysis) outside normal limits, as determined by PI. 17. 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). 18. Electrocardiography (EKG) indicative of 1st degree heart block, sinus tachycardia, left-axis deviation, non-specific ST or T-wave changes. 19. History of chest pain associated with cocaine use that prompted a visit to a physician. 20. Any medical or psychological condition that could jeopardize the subject's safe participation in the trial as determined by the PI.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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 |
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Within-subjects Design Varenicline, oral target dose of 1.0 mg BID, one week titration; placebo, matched for one week. Double-blind counterbalanced order | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Within-subjects Design |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 3 / 15 | 1 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
Visual Analog Scale Alcohol Craving
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
Population: Comparing alcohol craving during Varenicline treatment in participants initially treated with Varenicline (Group 1) to those initially treated with Placebo (Group 2).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Varenicline First, Then Placebo | Visual Analog Scale Alcohol Craving | 20 units on a scale |
| Placebo First, Then Varenicline | Visual Analog Scale Alcohol Craving | 35 units on a scale |
p-value: 0.02t-test, 2 sided
Primary
Visual Analog Scale Alcohol Craving 2
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
Population: Comparing alcohol craving during Placebo treatment in participants initially treated with Varenicline (Group 1) to those initially treated with Placebo (Group 2).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Varenicline First, Then Placebo | Visual Analog Scale Alcohol Craving 2 | 35 units on a scale |
| Placebo First, Then Varenicline | Visual Analog Scale Alcohol Craving 2 | 55 units on a scale |
p-value: 0.03t-test, 2 sided
Primary
Visual Analog Scale Cocaine Craving
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
Population: Comparing cocaine craving during Varenicline treatment in participants initially treated with Varenicline (Group 1) to those initially treated with Placebo (Group 2).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Varenicline First, Then Placebo | Visual Analog Scale Cocaine Craving | 25 units on a scale |
| Placebo First, Then Varenicline | Visual Analog Scale Cocaine Craving | 65 units on a scale |
p-value: 0.03t-test, 2 sided
Primary
Visual Analog Scale Cocaine Craving 2
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
Population: Comparing cocaine craving during Placebo treatment in participants initially treated with Varenicline (Group 1) to those initially treated with Placebo (Group 2).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Varenicline First, Then Placebo | Visual Analog Scale Cocaine Craving 2 | 65 units on a scale |
| Placebo First, Then Varenicline | Visual Analog Scale Cocaine Craving 2 | 80 units on a scale |
p-value: 0.04t-test, 2 sided