Alcoholism
Conditions
Keywords
Alcoholism, alcohol abuse, therapy, drug resistance, naltrexone, patient care management, human subject
Brief summary
This is a study involving treatment for alcohol dependence (alcoholism). The study will combine motivational enhancement therapy and cognitive behavioral therapy (combined behavioral intervention, or CBI) and tests the benefits of continued/discontinued treatment with naltrexone in a randomized placebo-controlled trial. CBI may have advantages in motivating patients to greater medication adherence and may address psychosocial factors that may limit the effects of naltrexone.
Detailed description
Naltrexone has been established as an efficacious medication to treat alcohol dependence but studies thus far have focused mostly on the acute phase of treatment rather than long-term management and have not offered alternative treatment strategies when patients do not respond to an initial course of naltrexone. For these initial non-responders to naltrexone, it is unclear what adjustments to treatment should be made to increase the likelihood of treatment success. We are unaware of previous research focused specifically on naltrexone non-response. Pilot data from ongoing trials at our center, however, suggest that up to a third of patients fail to respond to naltrexone. Moreover, these non-responsive patients go on to have the worst outcomes during the next 6 months of treatment if maintained on the same combination of naltrexone and medication management (MM). We propose to augment medication management with a combination of motivational enhancement therapy and cognitive behavioral therapy (combined behavioral intervention - CBI) and to test the benefits of continued/discontinued treatment with naltrexone in a randomized placebo-controlled trial. Clinical strategies for second line treatments often favor switching treatments rather than augmentation. However, there may be synergies between naltrexone and CBI that were not apparent with medication management. Specifically, CBI may have advantages in motivating patients to greater medication adherence (a leading cause of naltrexone treatment failure) and CBI may address psychosocial factors that limited or attenuated the effects of naltrexone.
Interventions
DRUGplacebo
placebo comparer for 16 weeks in phase 2.
DRUGNaltrexone
100mg/day, up to 8 weeks during Phase 1, 16 weeks in phase 2.
BEHAVIORALMedication Management (MM)
Brief manual-based therapy for up to 8 weeks during phase 1, 16 during phase 2.
BEHAVIORALCombined Behavioral Intervention (CBI)
45-60 minute sessions with a certified therapist focused on resolving ambivalence and skill building. Number of sessions guided by achievement of goals identified within treatment plan; minimum 9, maximum 20 sessions over 16 weeks.
BEHAVIORALTelephone Counseling
Bi-weekly telephone calls lasting 15-20 minutes focused on the same content as MM.
Sponsors
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years of age or older * Current DSM-IV diagnosis of alcohol dependence using the MINI. * Meets the following drinking criteria as measured by the Timeline Followback (TLFB): \* drank within 30 days of randomization; \* reports a minimum of 48 standard alcoholic drinks (avg. 12 drinks/wk.) in a consecutive 30-day period over the 90-day period prior to intake; and \* has 2 or more days of heavy drinking (defined as over 5 drinks per day in males and over 4 drinks per day in females) in this same pre-treatment period, prior to intake. * Prior to starting NTX, scores below 8 on the Clinical Inventory of Withdrawal from Alcohol (CIWA), and at least 3 consecutive days of abstinence (2 days abstinence will be permitted with approval by the principal investigator) directly prior to randomization, as determined by Subject report and breathalyzer measures * Speaks, understands and prints in English.
Exclusion criteria
* Has abused or been dependent on opiates in the past 12 months, or evidence of opiate use in month prior to treatment, as assessed by subject report and intake urine drug screen. Use of prescription opioids prior to treatment entry is allowed at the discretion of the investigator. However, subjects must be free from use at the time of randomization. * Meets DSM IV criteria for current dependence, abuse, or dependence in partial remission on any substance other than alcohol (except nicotine and marijuana). Subjects who test positive on the urine drug screen (with the exception of THC) at the initial visit (a repeat UDSis permitted in cases that are not clear. The repeat UDS should be at least 5 days after the initial test) * Has a lifetime DSM-IV diagnosis of schizophrenia or any psychotic disorder. Has a current DSM-IV diagnosis of post-traumatic stress disorder (PTST) or bipolar disorder, or any disorder that may interfere with study participation, at the discretion of the investigator. * Hepatocellular disease indicated by elevations of SGPT (ALT) and SGOT (AST) of at least 5 times normal, or elevated bilirubin (of 1.3 or higher), as evidenced by the most recent lab results prior to randomization. (documentation of Gilberts syndrome will not constitute an exclusion despite elevated bilirubin). * Has evidence of significant hematological, pulmonary, endocrine, cardiovascular, renal or gastrointestinal disease that the principal investigator considers a risk to participation. * Has taken any psychotropic medications (or disulfiram) regularly within the last seven days prior to randomization or needs immediate treatment with a psychotropic medication (with the exception of detoxification medications or benadryl used sparingly for sleep). The required washout period for fluoxetine (Prozac®) is 14 days prior to randomization, and the required washout period for other psychotropic medications is 7 days prior to randomization. * Has taken any detoxification medication on the day of randomization. * Tests positive on a pregnancy test, is contemplating pregnancy in the next 12 months, is nursing, or is not using an effective contraceptive method if the subject is of child-bearing potential.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Count of Responders and Non-responders in Phase 1 | 8 weeks | This is the number of patients who responded to phase 1 treatment based on the definition that subjects were randomly assigned to. |
| Percentage of Heavy Drinking Days | 16 weeks | Percentage of days with heavy drinking, where heavy drinking is 4 (5) or more drinks for females (males) in a 24 hour period. |
Countries
United States
Participant flow
Recruitment details
Study participants were recruited through advertisements in the local media, referrals from physicians, or self referrals.
Pre-assignment details
All participants were offered medically monitored outpatient detox as needed.
Participants by arm
| Arm | Count |
|---|---|
| Phase1: Liberal Definition B of heavy drinker: 5+ days of binge drinking | 152 |
| Phase1: Stringent Definition A of heavy drinker: 2+ days of binge drinking | 150 |
| Total | 302 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Phase1 | Lost to Follow-up | 16 | 23 | 0 | 0 | 0 | 0 |
| Phase1 | Withdrawal by Subject | 9 | 4 | 0 | 0 | 0 | 0 |
| Phase2 | Death | 0 | 0 | 1 | 0 | 0 | 1 |
| Phase2 | Lost to Follow-up | 0 | 0 | 12 | 14 | 4 | 10 |
| Phase2 | Withdrawal by Subject | 0 | 0 | 2 | 1 | 2 | 1 |
Baseline characteristics
| Characteristic | Phase1: Stringent | Total | Phase1: Liberal |
|---|---|---|---|
| Age, Continuous Age | 48.49 years STANDARD_DEVIATION 10.36 | 48.6 years STANDARD_DEVIATION 10.4 | 48.70 years STANDARD_DEVIATION 10.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 10 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 146 Participants | 292 Participants | 146 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 45 Participants | 85 Participants | 40 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 103 Participants | 214 Participants | 111 Participants |
| Sex: Female, Male Female | 20 Participants | 42 Participants | 22 Participants |
| Sex: Female, Male Male | 130 Participants | 260 Participants | 130 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 152 | 0 / 150 | 1 / 91 | 0 / 92 | 0 / 34 | 1 / 33 |
| other Total, other adverse events | 0 / 152 | 0 / 150 | 0 / 91 | 0 / 92 | 0 / 34 | 0 / 33 |
| serious Total, serious adverse events | 0 / 152 | 0 / 150 | 0 / 91 | 0 / 92 | 0 / 34 | 0 / 33 |
Outcome results
Primary
Count of Responders and Non-responders in Phase 1
This is the number of patients who responded to phase 1 treatment based on the definition that subjects were randomly assigned to.
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1 Liberal Response | Count of Responders and Non-responders in Phase 1 | 103 Participants |
| Phase 1 Stringent Response | Count of Responders and Non-responders in Phase 1 | 80 Participants |
Primary
Percentage of Heavy Drinking Days
Percentage of days with heavy drinking, where heavy drinking is 4 (5) or more drinks for females (males) in a 24 hour period.
Time frame: 16 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1 Liberal Response | Percentage of Heavy Drinking Days | 0 percentage days of heavy drinking |
| Phase 1 Stringent Response | Percentage of Heavy Drinking Days | 0 percentage days of heavy drinking |
| Phase 2 Nalt, MM and CBI for NR | Percentage of Heavy Drinking Days | 27.7 percentage days of heavy drinking |
| Phase 2 Placebo, MM and CBI for NR | Percentage of Heavy Drinking Days | 17.8 percentage days of heavy drinking |