Alcohol Use Disorder
Conditions
Keywords
harm reduction, naltrexone, alcohol use disorder, homelessness
Brief summary
The goal of this study is to test the efficacy of extended-release naltrexone and harm reduction counseling in reducing alcohol-related harm among homeless people with alcohol dependence.
Detailed description
Homelessness and alcohol dependence are commonly co-occurring and serious public health issues. Unfortunately, abstinence-based alcohol treatment approaches are minimally effective in engaging and successfully treating homeless individuals with alcohol dependence. There have therefore been calls for more flexible and client-centered approaches tailored to this population's needs. Innovative, low-barrier approaches (e.g., Housing First and alcohol management programs) have been applied with this population and are efficacious in reducing alcohol use and related problems as well as utilization of publicly funded services and associated costs. Such approaches have been referred to as harm-reduction interventions because they focus on reducing alcohol-related harm for affected individuals and their communities without requiring a commitment to abstinence-based goals. Although psychosocial, harm-reduction approaches are beginning to proliferate for this population, there are few pharmacological counterparts to support and enhance these efforts. One medication that could address this treatment gap is extended-release naltrexone (XR-NTX; marketed as Vivitrol®). XR-NTX is a 30-day, extended release formulation of the opioid receptor antagonist, naltrexone, and is administered monthly via gluteal intramuscular injection. The proposed Phase II study features a four-arm RCT (N=300) designed to test the efficacy of XR-NTX as a pharmacological adjunct to existing psychosocial harm-reduction services provided by community agencies to homeless people with alcohol dependence. The proposed study will include a 24-week follow-up and will test the relative efficacy of 3 active treatment combinations-1) XR-NTX+harm reduction counseling, 2) placebo+harm reduction counseling and 3) harm reduction counseling only (HRC)-compared to the services as usual (TAU) that all participants receive from community agencies. This proposed design will allow us to dismantle active treatment components and thereby detect potential placebo effects of both the administration of an injection and attention from a medical professional. In this study, there are three primary specific aims. First, we will test the relative efficacy of XR-NTX, placebo and HRC compared to TAU in decreasing alcohol quantity, frequency and alcohol-related problems. Second, we will test hypothesized mediators of the intervention effects. Specifically, we hypothesize that the active treatments will precipitate increases in motivation to change and decreases in craving, which, in turn, will mediate the active treatment effects on alcohol outcomes. Finally, we will test treatment effects on publicly funded service costs (i.e., emergency medical services, ER visits, hospital admissions, and county jail). It is hypothesized that XR-NTX, placebo and HRC groups will show greater decreases in publicly funded service costs than the TAU group.
Interventions
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Alkermes, Inc.
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Masking of the double-blind portion of the study was quadruple until after all data had been collected, when they were unblinded.
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* being a registered client at one of the named partnering sites * being at least 21 years of age (for legal reasons) * agreeing to use an adequate form of birth control (if female and in childbearing years) fulfilling criteria for current alcohol dependence according to DSM-IV-TR criteria as determined by the SCID-I/P
Exclusion criteria
* refusal or inability to consent to participation in research * constituting a risk to safety and security of other clients or staff * known sensitivity or allergy to naltrexone/XR-NTX * current treatment with naltrexone/XR-NTX * being pregnant or nursing * suicide attempts within the past year * renal insufficiency/serum creatinine level \> 1.5 * current opioid dependence according to the DSM-IV-TR criteria * liver transaminases (AST, ALT) \> 5 times the upper limit of normal (ULN) * clinical diagnosis of decompensated liver disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Alcohol Frequency | baseline, week 0, week 4, week 8, week 12, week 24, week 36 | Addiction Severity Index (ASI - 5th edition) will be used to assess frequency of alcohol use in the past 30 days. |
| Alcohol Quantity | Baseline, week 4, week 8, week 12, week 24, week 36 | Using the Alcohol Quantity and Use Assessment, we will collect data on peak alcohol quantity. |
| Alcohol-related Harm | Baseline, week 4, week 8, week 12, week 24, week 36 | Using the Short Inventory of Problems, we collected data on alcohol-related harm in the past month. The range of possible scores on the single summary score is 0-45, and higher scores indicate a greater experience of alcohol-related harm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Publicly Funded Service Utilization Costs | 2yr pretest, 12-week treatment period, 24-week follow-up period | Administrative data on publicly funded service utilization will be obtained from the King County Correctional Facility, King County Medic One/Emergency Medical Services, Harborview Medical Center (HMC), and the Washington State Comprehensive Hospital Abstract Reporting System (CHARS) for the 2-year pre-study period through the 24-week follow-up. We will obtain participant consent and HIPAA authorizations for these data at the information session. We will collect the following data: a) number of Medic One/EMS dispatches and associated costs; b) number of ER visits and associated costs; c) number of inpatient hospital admissions and total costs per admission (CHARS and HMC); d) number of bookings, length of stay and daily cost for the King County Correctional Facility. These data will be used to create overall cost outcomes. |
| Motivation to Change Ruler | baseline, week 4, week 8, week 12, week 24, week 36 | Motivation to change will be measured using the 10-point motivation ruler, where the stem was How motivated are you to make changes in your drinking to reduce harm? and 1= not at all motivated and 10=totally motivated. Thus, higher scores correspond to higher motivation for alcohol harm reduction |
| Alcohol Craving | baseline, week 4, week 8, week 12, week 24, week 36 | Alcohol craving will be measured using the psychometrically valid, 5-item, 6-point Likert-scale Penn Alcohol Craving Scale (PACS). The score ranges from 0-30, with higher scores representing a higher level of craving. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events Due to the Study Medication | baseline, week 4, week 8, week 12, week 24, week 36 | The Systematic Assessment for Treatment Emergent Effects (SAFTEE) interview,68,69 which was tailored for use with this medication, includes open-ended, categorical and Likert-scale questions assessing symptoms that correspond to potential adverse events associated with XR-NTX. This measure will be embedded in the CRF and will be used to establish tolerability of the study medication. For these descriptive scores, we took the average count of adverse events reported at each time point during the study. This was a total summary score ranging from 0 to 20, where a higher score represents a higher number of adverse events experienced. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Assessment-only Assessment-only control condition | 77 |
| HRC - Harm Reduction Counseling Harm reduction counseling, which entails provision of feedback and support of harm reduction goals and safer drinking provided at one-month intervals over a 3-month period.
HRC | 79 |
| XR-NTX+HRC 3 doses of active medication (380 mg injection/month) + Harm reduction counseling at one-month intervals over three months.
XR-NTX+HRC | 74 |
| Placebo+HRC 3 doses of placebo + harm reduction counseling at one-month intervals over a three-month period
Placebo+HRC | 78 |
| Total | 308 |
Baseline characteristics
| Characteristic | Assessment-only | HRC - Harm Reduction Counseling | XR-NTX+HRC | Placebo+HRC | Total |
|---|---|---|---|---|---|
| Age, Continuous | 47.51 years STANDARD_DEVIATION 9.5 | 49.38 years STANDARD_DEVIATION 7.35 | 49.27 years STANDARD_DEVIATION 9.11 | 46.55 years STANDARD_DEVIATION 10.46 | 48.17 years STANDARD_DEVIATION 9.21 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 11 Participants | 6 Participants | 7 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 67 Participants | 67 Participants | 68 Participants | 71 Participants | 273 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 18 Participants | 13 Participants | 11 Participants | 8 Participants | 50 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 24 Participants | 33 Participants | 28 Participants | 101 Participants |
| Race (NIH/OMB) More than one race | 14 Participants | 10 Participants | 8 Participants | 13 Participants | 45 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 8 Participants | 1 Participants | 4 Participants | 13 Participants |
| Race (NIH/OMB) White | 28 Participants | 24 Participants | 20 Participants | 24 Participants | 96 Participants |
| Sex: Female, Male Female | 16 Participants | 13 Participants | 11 Participants | 10 Participants | 50 Participants |
| Sex: Female, Male Male | 61 Participants | 66 Participants | 63 Participants | 68 Participants | 258 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 77 | 0 / 79 | 0 / 78 | 0 / 74 |
| other Total, other adverse events | 1 / 77 | 1 / 79 | 1 / 78 | 3 / 74 |
| serious Total, serious adverse events | 16 / 77 | 18 / 79 | 19 / 78 | 18 / 74 |
Outcome results
Primary
Alcohol Frequency
Addiction Severity Index (ASI - 5th edition) will be used to assess frequency of alcohol use in the past 30 days.
Time frame: baseline, week 0, week 4, week 8, week 12, week 24, week 36
Population: see https://doi.org/10.1016/s2215-0366(20)30489-2
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Assessment-only | Alcohol Frequency | Week 24 | 16.2 Drinking days per month | Standard Deviation 11.82 |
| Assessment-only | Alcohol Frequency | Week 4 | 17.87 Drinking days per month | Standard Deviation 10.85 |
| Assessment-only | Alcohol Frequency | Week 36 | 15.65 Drinking days per month | Standard Deviation 11.58 |
| Assessment-only | Alcohol Frequency | Week 8 | 17.18 Drinking days per month | Standard Deviation 11.83 |
| Assessment-only | Alcohol Frequency | Week 12 | 15.15 Drinking days per month | Standard Deviation 11.33 |
| Assessment-only | Alcohol Frequency | Baseline | 23.08 Drinking days per month | Standard Deviation 7.55 |
| HRC (Harm Reduction Counseling) | Alcohol Frequency | Week 8 | 18.67 Drinking days per month | Standard Deviation 11.22 |
| HRC (Harm Reduction Counseling) | Alcohol Frequency | Baseline | 24.63 Drinking days per month | Standard Deviation 8.02 |
| HRC (Harm Reduction Counseling) | Alcohol Frequency | Week 24 | 18.94 Drinking days per month | Standard Deviation 11.68 |
| HRC (Harm Reduction Counseling) | Alcohol Frequency | Week 12 | 18.68 Drinking days per month | Standard Deviation 11.45 |
| HRC (Harm Reduction Counseling) | Alcohol Frequency | Week 36 | 16.88 Drinking days per month | Standard Deviation 11.12 |
| HRC (Harm Reduction Counseling) | Alcohol Frequency | Week 4 | 18.81 Drinking days per month | Standard Deviation 11.45 |
| XR-NTX+HRC | Alcohol Frequency | Week 36 | 15.02 Drinking days per month | Standard Deviation 11.75 |
| XR-NTX+HRC | Alcohol Frequency | Week 4 | 17.43 Drinking days per month | Standard Deviation 10.91 |
| XR-NTX+HRC | Alcohol Frequency | Week 12 | 15.32 Drinking days per month | Standard Deviation 11.97 |
| XR-NTX+HRC | Alcohol Frequency | Week 8 | 18 Drinking days per month | Standard Deviation 11.8 |
| XR-NTX+HRC | Alcohol Frequency | Baseline | 23.42 Drinking days per month | Standard Deviation 8.63 |
| XR-NTX+HRC | Alcohol Frequency | Week 24 | 13.04 Drinking days per month | Standard Deviation 11.66 |
| Placebo+HRC | Alcohol Frequency | Week 36 | 14.59 Drinking days per month | Standard Deviation 11.51 |
| Placebo+HRC | Alcohol Frequency | Baseline | 23.35 Drinking days per month | Standard Deviation 8.66 |
| Placebo+HRC | Alcohol Frequency | Week 4 | 22.37 Drinking days per month | Standard Deviation 10.46 |
| Placebo+HRC | Alcohol Frequency | Week 8 | 20.83 Drinking days per month | Standard Deviation 10.51 |
| Placebo+HRC | Alcohol Frequency | Week 12 | 17.15 Drinking days per month | Standard Deviation 10.98 |
| Placebo+HRC | Alcohol Frequency | Week 24 | 17.93 Drinking days per month | Standard Deviation 11.91 |
Comparison: We used piecewise growth modeling to test various treatment arm effects on this outcome. Because there is currently no appropriate way to report on piecewise growth models in clinicaltrials.gov reporting tables, we are reporting the omnibus model statistics on this page called analysis 1 and select parameters representing certain treatment arm effects on subsequent analysis pages. However, we note these do not constitute separate analyses, but various parameters within a single SEM model.p-value: 0.028Chi-squared
Comparison: These are select parameters for treatment arm effects that are subordinate to the omnibus model statistics in the table called analysis 1. These are not separate analyses, but select parameters within a single SEM model. For more familiar formats, please see the related publications page, especially see https://doi.org/10.1016/s2215-0366(20)30489-2p-value: 0.04795% CI: [-8.09, -0.76]z
Comparison: These are select parameters for treatment arm effects that are subordinate to the omnibus model statistics in the table called analysis 1. These are not separate analyses, but select parameters within a single SEM model. For more familiar formats, please see the related publications page, especially see https://doi.org/10.1016/s2215-0366(20)30489-2p-value: 0.00995% CI: [-9.72, -2.19]z
Comparison: These are select parameters for treatment arm effects that are subordinate to the omnibus model statistics in the table called analysis 1. These are not separate analyses, but select parameters within a single SEM model. For more familiar formats, please see the related publications page, especially see https://doi.org/10.1016/s2215-0366(20)30489-2p-value: 0.07295% CI: [-7.88, -0.36]z
Primary
Alcohol Quantity
Using the Alcohol Quantity and Use Assessment, we will collect data on peak alcohol quantity.
Time frame: Baseline, week 4, week 8, week 12, week 24, week 36
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Assessment-only | Alcohol Quantity | Week 24 | 16.77 number of drinks on peak occasion | Standard Deviation 3.36 |
| Assessment-only | Alcohol Quantity | Week 4 | 22.4 number of drinks on peak occasion | Standard Deviation 2.23 |
| Assessment-only | Alcohol Quantity | Week 36 | 13.94 number of drinks on peak occasion | Standard Deviation 3.42 |
| Assessment-only | Alcohol Quantity | Week 8 | 20.45 number of drinks on peak occasion | Standard Deviation 2.41 |
| Assessment-only | Alcohol Quantity | Week 12 | 16.80 number of drinks on peak occasion | Standard Deviation 3.16 |
| Assessment-only | Alcohol Quantity | Baseline | 27.37 number of drinks on peak occasion | Standard Deviation 1.98 |
| HRC (Harm Reduction Counseling) | Alcohol Quantity | Week 4 | 18.97 number of drinks on peak occasion | Standard Deviation 2.76 |
| HRC (Harm Reduction Counseling) | Alcohol Quantity | Baseline | 25.95 number of drinks on peak occasion | Standard Deviation 1.79 |
| HRC (Harm Reduction Counseling) | Alcohol Quantity | Week 8 | 15.85 number of drinks on peak occasion | Standard Deviation 2.56 |
| HRC (Harm Reduction Counseling) | Alcohol Quantity | Week 12 | 12.92 number of drinks on peak occasion | Standard Deviation 3.18 |
| HRC (Harm Reduction Counseling) | Alcohol Quantity | Week 36 | 14.31 number of drinks on peak occasion | Standard Deviation 3.46 |
| HRC (Harm Reduction Counseling) | Alcohol Quantity | Week 24 | 13.43 number of drinks on peak occasion | Standard Deviation 3.78 |
| XR-NTX+HRC | Alcohol Quantity | Baseline | 32.02 number of drinks on peak occasion | Standard Deviation 1.7 |
| XR-NTX+HRC | Alcohol Quantity | Week 4 | 18.18 number of drinks on peak occasion | Standard Deviation 2.41 |
| XR-NTX+HRC | Alcohol Quantity | Week 24 | 13.14 number of drinks on peak occasion | Standard Deviation 3.91 |
| XR-NTX+HRC | Alcohol Quantity | Week 12 | 12.81 number of drinks on peak occasion | Standard Deviation 3.3 |
| XR-NTX+HRC | Alcohol Quantity | Week 36 | 12.46 number of drinks on peak occasion | Standard Deviation 3.36 |
| XR-NTX+HRC | Alcohol Quantity | Week 8 | 13.56 number of drinks on peak occasion | Standard Deviation 3.15 |
| Placebo+HRC | Alcohol Quantity | Week 36 | 16.3 number of drinks on peak occasion | Standard Deviation 2.73 |
| Placebo+HRC | Alcohol Quantity | Baseline | 32.15 number of drinks on peak occasion | Standard Deviation 1.74 |
| Placebo+HRC | Alcohol Quantity | Week 4 | 21.33 number of drinks on peak occasion | Standard Deviation 2.32 |
| Placebo+HRC | Alcohol Quantity | Week 8 | 17.21 number of drinks on peak occasion | Standard Deviation 2.44 |
| Placebo+HRC | Alcohol Quantity | Week 12 | 19.09 number of drinks on peak occasion | Standard Deviation 2.28 |
| Placebo+HRC | Alcohol Quantity | Week 24 | 18.01 number of drinks on peak occasion | Standard Deviation 3.04 |
Comparison: We used piecewise growth modeling to test various treatment arm effects on this outcome. Because there is currently no appropriate way to report on piecewise growth models in clinicaltrials.gov reporting tables, we are reporting the omnibus model statistics on this page called analysis 1 and select parameters representing certain treatment arm effects on subsequent analysis pages. However, we note these do not constitute separate analyses, but various parameters within a single SEM model.p-value: 0.461Chi-squared
Comparison: These are select parameters for treatment arm effects that are subordinate to the omnibus model statistics in the table called analysis 1. These are not separate analyses, but select parameters within a single SEM model. For more familiar formats, please see the related publications page, especially see https://doi.org/10.1016/s2215-0366(20)30489-2p-value: 0.0195% CI: [-0.79, -0.18]z score for parameters
Comparison: These are select parameters for treatment arm effects that are subordinate to the omnibus model statistics in the table called analysis 1. These are not separate analyses, but select parameters within a single SEM model. For more familiar formats, please see the related publications page, especially see https://doi.org/10.1016/s2215-0366(20)30489-2p-value: 0.0195% CI: [-0.67, -0.15]z
Comparison: These are select parameters for treatment arm effects that are subordinate to the omnibus model statistics in the table called analysis 1. These are not separate analyses, but select parameters within a single SEM model. For more familiar formats, please see the related publications page, especially see https://doi.org/10.1016/s2215-0366(20)30489-2p-value: 0.1995% CI: [-0.52, 0.06]z
Primary
Alcohol-related Harm
Using the Short Inventory of Problems, we collected data on alcohol-related harm in the past month. The range of possible scores on the single summary score is 0-45, and higher scores indicate a greater experience of alcohol-related harm.
Time frame: Baseline, week 4, week 8, week 12, week 24, week 36
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Assessment-only | Alcohol-related Harm | Baseline | 23.7 score on a scale | Standard Deviation 12.03 |
| Assessment-only | Alcohol-related Harm | Week 4 | 15.33 score on a scale | Standard Deviation 11.59 |
| Assessment-only | Alcohol-related Harm | Week 8 | 13.98 score on a scale | Standard Deviation 12.48 |
| Assessment-only | Alcohol-related Harm | Week 12 | 12.15 score on a scale | Standard Deviation 11.25 |
| Assessment-only | Alcohol-related Harm | Week 24 | 12.76 score on a scale | Standard Deviation 12.97 |
| Assessment-only | Alcohol-related Harm | Week 36 | 13.35 score on a scale | Standard Deviation 12.5 |
| HRC (Harm Reduction Counseling) | Alcohol-related Harm | Week 36 | 13.19 score on a scale | Standard Deviation 13.4 |
| HRC (Harm Reduction Counseling) | Alcohol-related Harm | Week 12 | 16.08 score on a scale | Standard Deviation 13.2 |
| HRC (Harm Reduction Counseling) | Alcohol-related Harm | Baseline | 23 score on a scale | Standard Deviation 12.05 |
| HRC (Harm Reduction Counseling) | Alcohol-related Harm | Week 8 | 15.52 score on a scale | Standard Deviation 12.85 |
| HRC (Harm Reduction Counseling) | Alcohol-related Harm | Week 4 | 17 score on a scale | Standard Deviation 11.43 |
| HRC (Harm Reduction Counseling) | Alcohol-related Harm | Week 24 | 15.89 score on a scale | Standard Deviation 13.88 |
| XR-NTX+HRC | Alcohol-related Harm | Week 4 | 17.98 score on a scale | Standard Deviation 12.51 |
| XR-NTX+HRC | Alcohol-related Harm | Week 8 | 17.15 score on a scale | Standard Deviation 11.97 |
| XR-NTX+HRC | Alcohol-related Harm | Week 12 | 15.5 score on a scale | Standard Deviation 13.03 |
| XR-NTX+HRC | Alcohol-related Harm | Week 36 | 16.87 score on a scale | Standard Deviation 14.54 |
| XR-NTX+HRC | Alcohol-related Harm | Week 24 | 17.9 score on a scale | Standard Deviation 16.19 |
| XR-NTX+HRC | Alcohol-related Harm | Baseline | 25.69 score on a scale | Standard Deviation 10.25 |
| Placebo+HRC | Alcohol-related Harm | Week 24 | 16.15 score on a scale | Standard Deviation 11.99 |
| Placebo+HRC | Alcohol-related Harm | Week 36 | 16.36 score on a scale | Standard Deviation 13.62 |
| Placebo+HRC | Alcohol-related Harm | Week 4 | 21.39 score on a scale | Standard Deviation 13.67 |
| Placebo+HRC | Alcohol-related Harm | Week 12 | 21 score on a scale | Standard Deviation 14.06 |
| Placebo+HRC | Alcohol-related Harm | Baseline | 22.7 score on a scale | Standard Deviation 12.05 |
| Placebo+HRC | Alcohol-related Harm | Week 8 | 18.31 score on a scale | Standard Deviation 14.15 |
Comparison: We used piecewise growth modeling to test various treatment arm effects on this outcome. Because there is currently no appropriate way to report on piecewise growth models in clinicaltrials.gov reporting tables, we are reporting the omnibus model statistics on this page called analysis 1 and select parameters representing certain treatment arm effects on subsequent analysis pages. However, we note these do not constitute separate analyses, but various parameters within a single SEM model.p-value: 0.347Chi-squared
Comparison: These are select parameters for treatment arm effects that are subordinate to the omnibus model statistics in the table called analysis 1. These are not separate analyses, but select parameters within a single SEM model. For more familiar formats, please see the related publications page, especially see https://doi.org/10.1016/s2215-0366(20)30489-2p-value: 0.00295% CI: [-3.39, -1.06]z
Comparison: These are select parameters for treatment arm effects that are subordinate to the omnibus model statistics in the table called analysis 1. These are not separate analyses, but select parameters within a single SEM model. For more familiar formats, please see the related publications page, especially see https://doi.org/10.1016/s2215-0366(20)30489-2p-value: 0.20895% CI: [-1.89, 0.25]z
Comparison: These are select parameters for treatment arm effects that are subordinate to the omnibus model statistics in the table called analysis 1. These are not separate analyses, but select parameters within a single SEM model. For more familiar formats, please see the related publications page, especially see https://doi.org/10.1016/s2215-0366(20)30489-2p-value: 0.02595% CI: [-2.73, -0.42]z
Secondary
Alcohol Craving
Alcohol craving will be measured using the psychometrically valid, 5-item, 6-point Likert-scale Penn Alcohol Craving Scale (PACS). The score ranges from 0-30, with higher scores representing a higher level of craving.
Time frame: baseline, week 4, week 8, week 12, week 24, week 36
Population: see https://doi.org/10.1016/s2215-0366(20)30489-2
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Assessment-only | Alcohol Craving | Week 24 | 15.98 score on a scale | Standard Deviation 10.01 |
| Assessment-only | Alcohol Craving | Week 4 | 18.54 score on a scale | Standard Deviation 7.15 |
| Assessment-only | Alcohol Craving | Week 36 | 13.74 score on a scale | Standard Deviation 9.18 |
| Assessment-only | Alcohol Craving | Week 8 | 16.6 score on a scale | Standard Deviation 8.83 |
| Assessment-only | Alcohol Craving | Week 12 | 16.59 score on a scale | Standard Deviation 9.77 |
| Assessment-only | Alcohol Craving | Baseline | 20.74 score on a scale | Standard Deviation 7.68 |
| HRC (Harm Reduction Counseling) | Alcohol Craving | Week 8 | 15.8 score on a scale | Standard Deviation 8.92 |
| HRC (Harm Reduction Counseling) | Alcohol Craving | Week 24 | 15.49 score on a scale | Standard Deviation 8.44 |
| HRC (Harm Reduction Counseling) | Alcohol Craving | Week 12 | 14.93 score on a scale | Standard Deviation 8.74 |
| HRC (Harm Reduction Counseling) | Alcohol Craving | Week 36 | 14.87 score on a scale | Standard Deviation 9.09 |
| HRC (Harm Reduction Counseling) | Alcohol Craving | Baseline | 21.99 score on a scale | Standard Deviation 6.18 |
| HRC (Harm Reduction Counseling) | Alcohol Craving | Week 4 | 17.85 score on a scale | Standard Deviation 8.15 |
| XR-NTX+HRC | Alcohol Craving | Week 24 | 17.09 score on a scale | Standard Deviation 9.05 |
| XR-NTX+HRC | Alcohol Craving | Week 4 | 17.5 score on a scale | Standard Deviation 9.11 |
| XR-NTX+HRC | Alcohol Craving | Week 12 | 17.2 score on a scale | Standard Deviation 8.53 |
| XR-NTX+HRC | Alcohol Craving | Week 8 | 16.15 score on a scale | Standard Deviation 9.04 |
| XR-NTX+HRC | Alcohol Craving | Baseline | 21.46 score on a scale | Standard Deviation 6.9 |
| XR-NTX+HRC | Alcohol Craving | Week 36 | 14.71 score on a scale | Standard Deviation 9.09 |
| Placebo+HRC | Alcohol Craving | Week 36 | 14.96 score on a scale | Standard Deviation 8.3 |
| Placebo+HRC | Alcohol Craving | Baseline | 21.70 score on a scale | Standard Deviation 5.79 |
| Placebo+HRC | Alcohol Craving | Week 4 | 17.19 score on a scale | Standard Deviation 8.1 |
| Placebo+HRC | Alcohol Craving | Week 8 | 16 score on a scale | Standard Deviation 8.74 |
| Placebo+HRC | Alcohol Craving | Week 12 | 15.25 score on a scale | Standard Deviation 8.1 |
| Placebo+HRC | Alcohol Craving | Week 24 | 13.76 score on a scale | Standard Deviation 9.13 |
Comparison: This was a mediation analysis (i.e., multiplication of regression coefficients for the regression of the craving (PACS) slope on group (a-paths) and for the regression of alcohol outcome slopes on readiness (b-paths), where a\*b is considered the mediated effect) for during-treatment effects (baseline to week 12).p-value: 0.65z
Comparison: This was a mediation analysis (i.e., multiplication of regression coefficients for the regression of the alcohol craving (PACS) slope on group (a-paths) and for the regression of alcohol outcome slopes on readiness (b-paths), where a\*b is considered the mediated effect) for during-treatment effects (baseline to week 12).p-value: 0.46z
Comparison: This was a mediation analysis (i.e., multiplication of regression coefficients for the regression of alcohol craving (PACS) slope on group (a-paths) and for the regression of alcohol outcome slopes on readiness (b-paths), where a\*b is considered the mediated effect) for during-treatment effects (baseline to week 12).p-value: 0.45z
Secondary
Motivation to Change Ruler
Motivation to change will be measured using the 10-point motivation ruler, where the stem was How motivated are you to make changes in your drinking to reduce harm? and 1= not at all motivated and 10=totally motivated. Thus, higher scores correspond to higher motivation for alcohol harm reduction
Time frame: baseline, week 4, week 8, week 12, week 24, week 36
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Assessment-only | Motivation to Change Ruler | Baseline | 6.64 score on a scale | Standard Deviation 2.97 |
| Assessment-only | Motivation to Change Ruler | Week 4 | 6.37 score on a scale | Standard Deviation 3 |
| Assessment-only | Motivation to Change Ruler | Week 8 | 6.39 score on a scale | Standard Deviation 3.1 |
| Assessment-only | Motivation to Change Ruler | Week 12 | 6.08 score on a scale | Standard Deviation 3.33 |
| Assessment-only | Motivation to Change Ruler | Week 24 | 7.3 score on a scale | Standard Deviation 3.07 |
| Assessment-only | Motivation to Change Ruler | Week 36 | 7.34 score on a scale | Standard Deviation 3.16 |
| HRC (Harm Reduction Counseling) | Motivation to Change Ruler | Week 36 | 6.85 score on a scale | Standard Deviation 3.19 |
| HRC (Harm Reduction Counseling) | Motivation to Change Ruler | Week 12 | 7.07 score on a scale | Standard Deviation 3.14 |
| HRC (Harm Reduction Counseling) | Motivation to Change Ruler | Baseline | 7.49 score on a scale | Standard Deviation 2.69 |
| HRC (Harm Reduction Counseling) | Motivation to Change Ruler | Week 8 | 7.48 score on a scale | Standard Deviation 2.62 |
| HRC (Harm Reduction Counseling) | Motivation to Change Ruler | Week 4 | 6.98 score on a scale | Standard Deviation 3.11 |
| HRC (Harm Reduction Counseling) | Motivation to Change Ruler | Week 24 | 6.92 score on a scale | Standard Deviation 3.03 |
| XR-NTX+HRC | Motivation to Change Ruler | Week 4 | 6.43 score on a scale | Standard Deviation 3.06 |
| XR-NTX+HRC | Motivation to Change Ruler | Week 8 | 7.13 score on a scale | Standard Deviation 2.79 |
| XR-NTX+HRC | Motivation to Change Ruler | Week 12 | 6.32 score on a scale | Standard Deviation 3.32 |
| XR-NTX+HRC | Motivation to Change Ruler | Week 36 | 6.71 score on a scale | Standard Deviation 3.3 |
| XR-NTX+HRC | Motivation to Change Ruler | Week 24 | 6.87 score on a scale | Standard Deviation 3.1 |
| XR-NTX+HRC | Motivation to Change Ruler | Baseline | 7.05 score on a scale | Standard Deviation 2.94 |
| Placebo+HRC | Motivation to Change Ruler | Week 24 | 6.59 score on a scale | Standard Deviation 3.3 |
| Placebo+HRC | Motivation to Change Ruler | Week 36 | 6.81 score on a scale | Standard Deviation 3.07 |
| Placebo+HRC | Motivation to Change Ruler | Week 4 | 6.61 score on a scale | Standard Deviation 3.02 |
| Placebo+HRC | Motivation to Change Ruler | Week 12 | 6.64 score on a scale | Standard Deviation 3.05 |
| Placebo+HRC | Motivation to Change Ruler | Baseline | 6.42 score on a scale | Standard Deviation 3.06 |
| Placebo+HRC | Motivation to Change Ruler | Week 8 | 6.33 score on a scale | Standard Deviation 3.05 |
Comparison: This was a mediation analysis (i.e., multiplication of regression coefficients for the regression of readiness for change slope on group (a-paths) and for the regression of alcohol outcome slopes on readiness (b-paths), where a\*b is considered the mediated effect) for during-treatment effects (baseline to week 12).p-value: 0.6z
Comparison: This was a mediation analysis (i.e., multiplication of regression coefficients for the regression of readiness for change slope on group (a-paths) and for the regression of alcohol outcome slopes on readiness (b-paths), where a\*b is considered the mediated effect) for during-treatment effects (baseline to week 12).p-value: 0.83z
Comparison: This was a mediation analysis (i.e., multiplication of regression coefficients for the regression of readiness for change slope on group (a-paths) and for the regression of alcohol outcome slopes on readiness (b-paths), where a\*b is considered the mediated effect) for during-treatment effects (baseline to week 12).p-value: 0.89z
Comparison: This was a mediation analysis (i.e., multiplication of regression coefficients for the regression of readiness for change slope on group (a-paths) and for the regression of alcohol outcome slopes on readiness (b-paths), where a\*b is considered the mediated effect) for during-treatment effects (baseline to week 12).p-value: 0.65z
Comparison: This was a mediation analysis (i.e., multiplication of regression coefficients for the regression of readiness for change slope on group (a-paths) and for the regression of alcohol outcome slopes on readiness (b-paths), where a\*b is considered the mediated effect) for during-treatment effects (baseline to week 12).p-value: 0.87z
Comparison: This was a mediation analysis (i.e., multiplication of regression coefficients for the regression of readiness for change slope on group (a-paths) and for the regression of alcohol outcome slopes on readiness (b-paths), where a\*b is considered the mediated effect) for during-treatment effects (baseline to week 12).p-value: 0.91z
Comparison: This was a mediation analysis (i.e., multiplication of regression coefficients for the regression of readiness for change slope on group (a-paths) and for the regression of alcohol outcome slopes on readiness (b-paths), where a\*b is considered the mediated effect) for during-treatment effects (baseline to week 12).p-value: 0.54z
Comparison: This was a mediation analysis (i.e., multiplication of regression coefficients for the regression of readiness for change slope on group (a-paths) and for the regression of alcohol outcome slopes on readiness (b-paths), where a\*b is considered the mediated effect) for during-treatment effects (baseline to week 12).p-value: 0.84z
Comparison: This was a mediation analysis (i.e., multiplication of regression coefficients for the regression of readiness for change slope on group (a-paths) and for the regression of alcohol outcome slopes on readiness (b-paths), where a\*b is considered the mediated effect) for during-treatment effects (baseline to week 12).p-value: 0.84z
Secondary
Publicly Funded Service Utilization Costs
Administrative data on publicly funded service utilization will be obtained from the King County Correctional Facility, King County Medic One/Emergency Medical Services, Harborview Medical Center (HMC), and the Washington State Comprehensive Hospital Abstract Reporting System (CHARS) for the 2-year pre-study period through the 24-week follow-up. We will obtain participant consent and HIPAA authorizations for these data at the information session. We will collect the following data: a) number of Medic One/EMS dispatches and associated costs; b) number of ER visits and associated costs; c) number of inpatient hospital admissions and total costs per admission (CHARS and HMC); d) number of bookings, length of stay and daily cost for the King County Correctional Facility. These data will be used to create overall cost outcomes.
Time frame: 2yr pretest, 12-week treatment period, 24-week follow-up period
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Assessment-only | Publicly Funded Service Utilization Costs | Pretest | 722.32 US dollars | Standard Deviation 1054.45 |
| Assessment-only | Publicly Funded Service Utilization Costs | Follow-up | 1576.97 US dollars | Standard Deviation 2871.47 |
| Assessment-only | Publicly Funded Service Utilization Costs | During treatment | 1371.51 US dollars | Standard Deviation 2649.4 |
| HRC (Harm Reduction Counseling) | Publicly Funded Service Utilization Costs | Pretest | 829.22 US dollars | Standard Deviation 1447.25 |
| HRC (Harm Reduction Counseling) | Publicly Funded Service Utilization Costs | Follow-up | 1326.28 US dollars | Standard Deviation 2967.28 |
| HRC (Harm Reduction Counseling) | Publicly Funded Service Utilization Costs | During treatment | 871.57 US dollars | Standard Deviation 1549.52 |
| XR-NTX+HRC | Publicly Funded Service Utilization Costs | During treatment | 913.43 US dollars | Standard Deviation 1384.25 |
| XR-NTX+HRC | Publicly Funded Service Utilization Costs | Pretest | 583.55 US dollars | Standard Deviation 707.79 |
| XR-NTX+HRC | Publicly Funded Service Utilization Costs | Follow-up | 1286.62 US dollars | Standard Deviation 2329.87 |
| Placebo+HRC | Publicly Funded Service Utilization Costs | Pretest | 511.62 US dollars | Standard Deviation 665.1 |
| Placebo+HRC | Publicly Funded Service Utilization Costs | Follow-up | 1277.21 US dollars | Standard Deviation 1876.49 |
| Placebo+HRC | Publicly Funded Service Utilization Costs | During treatment | 1516.09 US dollars | Standard Deviation 4274.35 |
Comparison: We used piecewise growth modeling to test various treatment arm effects on this outcome. Because there is currently no appropriate way to report on piecewise growth models in clinicaltrials.gov reporting tables, we are reporting the omnibus model statistics on this page called analysis 1 and select parameters representing certain treatment arm effects on subsequent analysis pages. However, we note these do not constitute separate analyses, but various parameters within a single SEM model.p-value: 0.95Chi-squared
Comparison: These are select parameters for treatment arm effects that are subordinate to the omnibus model statistics in the table called analysis 1. These are not separate analyses, but select parameters within a single SEM model.p-value: 0.7595% CI: [-0.24, 0.16]Chi-squared
Comparison: These are select parameters for treatment arm effects that are subordinate to the omnibus model statistics in the table called analysis 1. These are not separate analyses, but select parameters within a single SEM model.p-value: 0.295% CI: [-0.34, 0.04]Chi-squared
Comparison: These are select parameters for treatment arm effects that are subordinate to the omnibus model statistics in the table called analysis 1. These are not separate analyses, but select parameters within a single SEM model.p-value: 0.3995% CI: [-0.09, 0.29]Chi-squared
Other Pre-specified
Adverse Events Due to the Study Medication
The Systematic Assessment for Treatment Emergent Effects (SAFTEE) interview,68,69 which was tailored for use with this medication, includes open-ended, categorical and Likert-scale questions assessing symptoms that correspond to potential adverse events associated with XR-NTX. This measure will be embedded in the CRF and will be used to establish tolerability of the study medication. For these descriptive scores, we took the average count of adverse events reported at each time point during the study. This was a total summary score ranging from 0 to 20, where a higher score represents a higher number of adverse events experienced.
Time frame: baseline, week 4, week 8, week 12, week 24, week 36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Assessment-only | Adverse Events Due to the Study Medication | 4.5 mean scale score averaged during study | Standard Deviation 3.37 |
| HRC (Harm Reduction Counseling) | Adverse Events Due to the Study Medication | 4.88 mean scale score averaged during study | Standard Deviation 3.65 |
| XR-NTX+HRC | Adverse Events Due to the Study Medication | 5.11 mean scale score averaged during study | Standard Deviation 3.38 |
| Placebo+HRC | Adverse Events Due to the Study Medication | 4.96 mean scale score averaged during study | Standard Deviation 3.84 |
Comparison: We conducted a generalized estimating equations analysis (negative binomial distribution, log link) to test whether number of adverse events reported increased from baseline to the follow-ups differentially across placebo and XR-NTX groupsp-value: >0.8495% CI: [0.83, 1.16]z