Alcoholism
Conditions
Brief summary
The purpose of this study is to develop and validate a human laboratory model for prediction of medication efficacy in clinical trials for relapse prevention in alcohol dependence.
Detailed description
This is a double-blind, 3-cell, outpatient human laboratory study to determine the degree to which acamprosate and naltrexone will suppress subjective and physiological responsivity to alcohol cues relative to placebo in early abstinence.
Interventions
DRUGAcamprosate
Two 333mg capsules, 3 times daily (Total dose, 1998 mg daily), 1 week duration
DRUGNaltrexone
50mg capsule, Once daily, 1 week duration
DRUGPlacebo
Matched placebo capsule, 1 week duration
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
The Scripps Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Males or females ≥ 18 and ≤ 55 years of age * Meets Diagnostic and Statistical Manual-Fourth Edition (DSM-IV) criteria for current alcohol dependence * Does not desire treatment * Alcohol free, as verified by breath alcohol concentration, with a Clinical Institute Withdrawal Assessment (CIWA) ≤ 8, at the time of testing, with no evidence of drinking for at least 3 days but no more than 7 days prior to the cue reactivity session * Able to complete and understand questionnaires and study procedures in English * Verbal I.Q. estimate ≥ 85 * Signed informed consent
Exclusion criteria
* Currently meets DSM-IV criteria for dependence on substances other than alcohol or nicotine * Significant medical disorders that will increase potential risk or interfere with study participation * Sexually active women with childbearing potential who are pregnant, nursing, or refuse to use a reliable method of birth control * Meets DSM-IV criteria for a major Axis I disorder, including depression or anxiety disorders * Treatment within the month prior to screening with investigational medications or those which may influence drinking outcome, e.g., disulfiram (Antabuse), naltrexone (ReVia), acamprosate (Campral), antidepressants or other psychotropic agents * Chronic treatment with any narcotic-containing medications during the previous month or evidence of current opiate use * Liver function tests more than three times normal or elevated bilirubin * No fixed domicile and/or no availability by telephone or beeper * Current involvement in or plans for treatment prior to study completion * Patients who have a history of adverse drug reactions to the study drugs or their ingredients * Failure to take double-blind medication as prescribed * Inability to understand or comply with the provisions of the protocol or consent form
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Visual Analog Scale of Craving to Drink at 1 Week Following Administration of Acamprosate or Naltrexone or Placebo During the Double-Blind Period | 1 week | The four Visual Analog Scale questions assess domains of alcohol craving: the intention to drink, loss of control, relief craving, and urge intensity. The scale ranges from 0-20 where a zero indicates no craving and 20 indicates severe craving; thus, a higher score indicates a worse outcome. Total is a summation of the four subscales (i.e. Strength, Intent, Impulse, Relief) and ranges in value from 0-80 with higher scores indicative of a worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Standard Drinks Per Week at 1 Week | 1 week | Standard drinks are equivalent to 14 grams of pure alcohol and number of drinks are assessed with Timeline Follow-Back (TLFB) methods. Change = (Week 1 - Baseline). More negative values indicate less use of alcohol. |
| Change From Baseline in Mood on the Beck Depression Inventory (BDI-II) at Week 1 | 1 week | The BDI-II is a self-rating of severity of depressive symptoms. BDI-II Total scores range from 0-63; a lower score indicates less severe depressive systems and thus is a better outcome. Change = (Week 1 score - Baseline score). The Total score is a sum of the 21 items on the BDI-II instrument, with each item rated from 0-3. |
| Change From Baseline in Sleep Quality on the Pittsburgh Sleep Quality Index (PSQI) Total Score at Week 1 | 1 week | The PSQI is an instrument to assess subjective sleep quality and disturbance. The Total score ranges from 0 to 21 where a lower score is better sleep quality. Change = (Week 1 score - Baseline score). Seven subscales (range 0-3) are summed to compute the Total score. |
| Change From Screening in Craving on the Alcohol Craving Questionnaire-Short Form (ACQ-SF) Total Score at Week 1 | 2 weeks | The ACQ-SF is an assessment of current drinking urges, difficulty resisting urge and anticipation of positive outcome or relief from negative state by drinking. The Total score ranges from 0 to 7 where a lower score is a better outcome. Change = (Week 1 score - Screening score). The scale is comprised of twelve items (range 0-7) that are averaged to compute the Total score. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited for study participation at the Laboratory of Clinical Psychopharmacology at The Scripps Research Institute in La Jolla, California from 04/17/2008-12/10/2009. Sixty eight subjects were enrolled, and sixty two subjects completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Campral (Acamprosate) Acamprosate
Acamprosate: Total dose, 1998 mg daily, 1 week duration | 22 |
| ReVia (Naltrexone) Naltrexone
Naltrexone: 50mg capsule, Once daily, 1 week duration | 27 |
| Sugar Pill (Placebo) Placebo: Double-dummy placebo capsules, 1 week duration | 19 |
| Total | 68 |
Baseline characteristics
| Characteristic | Campral (Acamprosate) | ReVia (Naltrexone) | Sugar Pill (Placebo) | Total |
|---|---|---|---|---|
| Age, Continuous | 35.73 years STANDARD_DEVIATION 10.1 | 36.37 years STANDARD_DEVIATION 12.45 | 42.84 years STANDARD_DEVIATION 10.37 | 37.97 years STANDARD_DEVIATION 11.42 |
| Region of Enrollment United States | 22 participants | 27 participants | 19 participants | 68 participants |
| Sex: Female, Male Female | 10 Participants | 6 Participants | 6 Participants | 22 Participants |
| Sex: Female, Male Male | 12 Participants | 21 Participants | 13 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 20 | 9 / 25 | 3 / 17 |
| serious Total, serious adverse events | 0 / 20 | 0 / 25 | 0 / 17 |
Outcome results
Primary
Visual Analog Scale of Craving to Drink at 1 Week Following Administration of Acamprosate or Naltrexone or Placebo During the Double-Blind Period
The four Visual Analog Scale questions assess domains of alcohol craving: the intention to drink, loss of control, relief craving, and urge intensity. The scale ranges from 0-20 where a zero indicates no craving and 20 indicates severe craving; thus, a higher score indicates a worse outcome. Total is a summation of the four subscales (i.e. Strength, Intent, Impulse, Relief) and ranges in value from 0-80 with higher scores indicative of a worse outcome.
Time frame: 1 week
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Campral (Acamprosate) | Visual Analog Scale of Craving to Drink at 1 Week Following Administration of Acamprosate or Naltrexone or Placebo During the Double-Blind Period | Strength | 2.12 units on a scale | Standard Deviation 3.1 |
| Campral (Acamprosate) | Visual Analog Scale of Craving to Drink at 1 Week Following Administration of Acamprosate or Naltrexone or Placebo During the Double-Blind Period | Relief | 0.07 units on a scale | Standard Deviation 1.67 |
| Campral (Acamprosate) | Visual Analog Scale of Craving to Drink at 1 Week Following Administration of Acamprosate or Naltrexone or Placebo During the Double-Blind Period | Total | 5.00 units on a scale | Standard Deviation 6.24 |
| Campral (Acamprosate) | Visual Analog Scale of Craving to Drink at 1 Week Following Administration of Acamprosate or Naltrexone or Placebo During the Double-Blind Period | Intent | 1.65 units on a scale | Standard Deviation 1.56 |
| Campral (Acamprosate) | Visual Analog Scale of Craving to Drink at 1 Week Following Administration of Acamprosate or Naltrexone or Placebo During the Double-Blind Period | Impulse | 1.17 units on a scale | Standard Deviation 1.94 |
| ReVia (Naltrexone) | Visual Analog Scale of Craving to Drink at 1 Week Following Administration of Acamprosate or Naltrexone or Placebo During the Double-Blind Period | Intent | 2.99 units on a scale | Standard Deviation 3.67 |
| ReVia (Naltrexone) | Visual Analog Scale of Craving to Drink at 1 Week Following Administration of Acamprosate or Naltrexone or Placebo During the Double-Blind Period | Total | 10.09 units on a scale | Standard Deviation 12.12 |
| ReVia (Naltrexone) | Visual Analog Scale of Craving to Drink at 1 Week Following Administration of Acamprosate or Naltrexone or Placebo During the Double-Blind Period | Relief | 2.01 units on a scale | Standard Deviation 3.56 |
| ReVia (Naltrexone) | Visual Analog Scale of Craving to Drink at 1 Week Following Administration of Acamprosate or Naltrexone or Placebo During the Double-Blind Period | Strength | 3.40 units on a scale | Standard Deviation 3.87 |
| ReVia (Naltrexone) | Visual Analog Scale of Craving to Drink at 1 Week Following Administration of Acamprosate or Naltrexone or Placebo During the Double-Blind Period | Impulse | 1.69 units on a scale | Standard Deviation 2.78 |
| Sugar Pill (Placebo) | Visual Analog Scale of Craving to Drink at 1 Week Following Administration of Acamprosate or Naltrexone or Placebo During the Double-Blind Period | Relief | 3.57 units on a scale | Standard Deviation 4.14 |
| Sugar Pill (Placebo) | Visual Analog Scale of Craving to Drink at 1 Week Following Administration of Acamprosate or Naltrexone or Placebo During the Double-Blind Period | Total | 17.96 units on a scale | Standard Deviation 15.83 |
| Sugar Pill (Placebo) | Visual Analog Scale of Craving to Drink at 1 Week Following Administration of Acamprosate or Naltrexone or Placebo During the Double-Blind Period | Strength | 5.86 units on a scale | Standard Deviation 4.79 |
| Sugar Pill (Placebo) | Visual Analog Scale of Craving to Drink at 1 Week Following Administration of Acamprosate or Naltrexone or Placebo During the Double-Blind Period | Impulse | 4.31 units on a scale | Standard Deviation 4.82 |
| Sugar Pill (Placebo) | Visual Analog Scale of Craving to Drink at 1 Week Following Administration of Acamprosate or Naltrexone or Placebo During the Double-Blind Period | Intent | 4.22 units on a scale | Standard Deviation 4.34 |
Secondary
Change From Baseline in Mood on the Beck Depression Inventory (BDI-II) at Week 1
The BDI-II is a self-rating of severity of depressive symptoms. BDI-II Total scores range from 0-63; a lower score indicates less severe depressive systems and thus is a better outcome. Change = (Week 1 score - Baseline score). The Total score is a sum of the 21 items on the BDI-II instrument, with each item rated from 0-3.
Time frame: 1 week
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Campral (Acamprosate) | Change From Baseline in Mood on the Beck Depression Inventory (BDI-II) at Week 1 | BDI-II Total Week 1 | 4.75 units on a scale | Standard Deviation 4.81 |
| Campral (Acamprosate) | Change From Baseline in Mood on the Beck Depression Inventory (BDI-II) at Week 1 | BDI-II Total Baseline | 4.40 units on a scale | Standard Deviation 5.14 |
| Campral (Acamprosate) | Change From Baseline in Mood on the Beck Depression Inventory (BDI-II) at Week 1 | BDI-II Total Change | 0.35 units on a scale | Standard Deviation 4.16 |
| ReVia (Naltrexone) | Change From Baseline in Mood on the Beck Depression Inventory (BDI-II) at Week 1 | BDI-II Total Week 1 | 3.84 units on a scale | Standard Deviation 4.02 |
| ReVia (Naltrexone) | Change From Baseline in Mood on the Beck Depression Inventory (BDI-II) at Week 1 | BDI-II Total Baseline | 4.04 units on a scale | Standard Deviation 4.33 |
| ReVia (Naltrexone) | Change From Baseline in Mood on the Beck Depression Inventory (BDI-II) at Week 1 | BDI-II Total Change | -0.20 units on a scale | Standard Deviation 2.84 |
| Sugar Pill (Placebo) | Change From Baseline in Mood on the Beck Depression Inventory (BDI-II) at Week 1 | BDI-II Total Baseline | 3.53 units on a scale | Standard Deviation 4.74 |
| Sugar Pill (Placebo) | Change From Baseline in Mood on the Beck Depression Inventory (BDI-II) at Week 1 | BDI-II Total Change | 1.41 units on a scale | Standard Deviation 4.3 |
| Sugar Pill (Placebo) | Change From Baseline in Mood on the Beck Depression Inventory (BDI-II) at Week 1 | BDI-II Total Week 1 | 4.94 units on a scale | Standard Deviation 5.7 |
Secondary
Change From Baseline in Sleep Quality on the Pittsburgh Sleep Quality Index (PSQI) Total Score at Week 1
The PSQI is an instrument to assess subjective sleep quality and disturbance. The Total score ranges from 0 to 21 where a lower score is better sleep quality. Change = (Week 1 score - Baseline score). Seven subscales (range 0-3) are summed to compute the Total score.
Time frame: 1 week
Population: Seven participants who completed the double blind portion of the trial were unable to be analyzed for change in PSQI Total score due to incomplete PSQI questionnaire at baseline and/or Week 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Campral (Acamprosate) | Change From Baseline in Sleep Quality on the Pittsburgh Sleep Quality Index (PSQI) Total Score at Week 1 | PSQI Total Week 1 | 4.69 units on a scale | Standard Deviation 3.88 |
| Campral (Acamprosate) | Change From Baseline in Sleep Quality on the Pittsburgh Sleep Quality Index (PSQI) Total Score at Week 1 | PSQI Total Change | 0.19 units on a scale | Standard Deviation 3.78 |
| Campral (Acamprosate) | Change From Baseline in Sleep Quality on the Pittsburgh Sleep Quality Index (PSQI) Total Score at Week 1 | PSQI Total Baseline | 4.50 units on a scale | Standard Deviation 3.14 |
| ReVia (Naltrexone) | Change From Baseline in Sleep Quality on the Pittsburgh Sleep Quality Index (PSQI) Total Score at Week 1 | PSQI Total Change | -0.17 units on a scale | Standard Deviation 2.08 |
| ReVia (Naltrexone) | Change From Baseline in Sleep Quality on the Pittsburgh Sleep Quality Index (PSQI) Total Score at Week 1 | PSQI Total Baseline | 4.74 units on a scale | Standard Deviation 3.62 |
| ReVia (Naltrexone) | Change From Baseline in Sleep Quality on the Pittsburgh Sleep Quality Index (PSQI) Total Score at Week 1 | PSQI Total Week 1 | 4.57 units on a scale | Standard Deviation 3.55 |
| Sugar Pill (Placebo) | Change From Baseline in Sleep Quality on the Pittsburgh Sleep Quality Index (PSQI) Total Score at Week 1 | PSQI Total Change | 0.13 units on a scale | Standard Deviation 2.68 |
| Sugar Pill (Placebo) | Change From Baseline in Sleep Quality on the Pittsburgh Sleep Quality Index (PSQI) Total Score at Week 1 | PSQI Total Baseline | 4.25 units on a scale | Standard Deviation 2.82 |
| Sugar Pill (Placebo) | Change From Baseline in Sleep Quality on the Pittsburgh Sleep Quality Index (PSQI) Total Score at Week 1 | PSQI Total Week 1 | 4.38 units on a scale | Standard Deviation 3.67 |
Secondary
Change From Baseline in Standard Drinks Per Week at 1 Week
Standard drinks are equivalent to 14 grams of pure alcohol and number of drinks are assessed with Timeline Follow-Back (TLFB) methods. Change = (Week 1 - Baseline). More negative values indicate less use of alcohol.
Time frame: 1 week
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Campral (Acamprosate) | Change From Baseline in Standard Drinks Per Week at 1 Week | Drinks/week Baseline | 44.90 drinks/week | Standard Deviation 61.89 |
| Campral (Acamprosate) | Change From Baseline in Standard Drinks Per Week at 1 Week | Drinks/week Week 1 | 24.37 drinks/week | Standard Deviation 22.81 |
| Campral (Acamprosate) | Change From Baseline in Standard Drinks Per Week at 1 Week | Drinks/week Change | -20.53 drinks/week | Standard Deviation 60.68 |
| ReVia (Naltrexone) | Change From Baseline in Standard Drinks Per Week at 1 Week | Drinks/week Change | -21.23 drinks/week | Standard Deviation 23.93 |
| ReVia (Naltrexone) | Change From Baseline in Standard Drinks Per Week at 1 Week | Drinks/week Week 1 | 25.79 drinks/week | Standard Deviation 14.32 |
| ReVia (Naltrexone) | Change From Baseline in Standard Drinks Per Week at 1 Week | Drinks/week Baseline | 47.02 drinks/week | Standard Deviation 24.08 |
| Sugar Pill (Placebo) | Change From Baseline in Standard Drinks Per Week at 1 Week | Drinks/week Baseline | 48.87 drinks/week | Standard Deviation 58.53 |
| Sugar Pill (Placebo) | Change From Baseline in Standard Drinks Per Week at 1 Week | Drinks/week Week 1 | 21.51 drinks/week | Standard Deviation 18.88 |
| Sugar Pill (Placebo) | Change From Baseline in Standard Drinks Per Week at 1 Week | Drinks/week Change | -27.35 drinks/week | Standard Deviation 44.84 |
Secondary
Change From Screening in Craving on the Alcohol Craving Questionnaire-Short Form (ACQ-SF) Total Score at Week 1
The ACQ-SF is an assessment of current drinking urges, difficulty resisting urge and anticipation of positive outcome or relief from negative state by drinking. The Total score ranges from 0 to 7 where a lower score is a better outcome. Change = (Week 1 score - Screening score). The scale is comprised of twelve items (range 0-7) that are averaged to compute the Total score.
Time frame: 2 weeks
Population: One participant in the naltrexone arm who completed the double blind portion of the trial was unable to be analyzed for change in ACQ-SF Total score due to incomplete ACQ-SF questionnaire at Week 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Campral (Acamprosate) | Change From Screening in Craving on the Alcohol Craving Questionnaire-Short Form (ACQ-SF) Total Score at Week 1 | ACQ-SF Total Screening | 3.80 units on a scale | Standard Deviation 1.38 |
| Campral (Acamprosate) | Change From Screening in Craving on the Alcohol Craving Questionnaire-Short Form (ACQ-SF) Total Score at Week 1 | ACQ-SF Total Change | -0.44 units on a scale | Standard Deviation 1.02 |
| Campral (Acamprosate) | Change From Screening in Craving on the Alcohol Craving Questionnaire-Short Form (ACQ-SF) Total Score at Week 1 | ACQ-SF Total Week 1 | 3.36 units on a scale | Standard Deviation 1.28 |
| ReVia (Naltrexone) | Change From Screening in Craving on the Alcohol Craving Questionnaire-Short Form (ACQ-SF) Total Score at Week 1 | ACQ-SF Total Change | -0.12 units on a scale | Standard Deviation 1.56 |
| ReVia (Naltrexone) | Change From Screening in Craving on the Alcohol Craving Questionnaire-Short Form (ACQ-SF) Total Score at Week 1 | ACQ-SF Total Screening | 3.81 units on a scale | Standard Deviation 1.55 |
| ReVia (Naltrexone) | Change From Screening in Craving on the Alcohol Craving Questionnaire-Short Form (ACQ-SF) Total Score at Week 1 | ACQ-SF Total Week 1 | 3.69 units on a scale | Standard Deviation 1.26 |
| Sugar Pill (Placebo) | Change From Screening in Craving on the Alcohol Craving Questionnaire-Short Form (ACQ-SF) Total Score at Week 1 | ACQ-SF Total Screening | 3.99 units on a scale | Standard Deviation 1.34 |
| Sugar Pill (Placebo) | Change From Screening in Craving on the Alcohol Craving Questionnaire-Short Form (ACQ-SF) Total Score at Week 1 | ACQ-SF Total Change | -0.48 units on a scale | Standard Deviation 1.12 |
| Sugar Pill (Placebo) | Change From Screening in Craving on the Alcohol Craving Questionnaire-Short Form (ACQ-SF) Total Score at Week 1 | ACQ-SF Total Week 1 | 3.51 units on a scale | Standard Deviation 0.98 |