Oral vs. Injectable Naltrexone for Hospitalized Veterans With Alcohol Dependence

Study Overview
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Brief Summary
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The over-arching goal of the proposed project is to understand the impact of medication adherence upon engagement in behavioral treatment for alcohol use disorders. The proposed project is a pilot feasibility study of inpatient veterans with problem alcohol use at the William S. Middleton VA Hospital (Madison, WI). Participants will be randomized to one of two parallel study conditions: (1) an initial 50 mg oral dose of naltrexone prior to hospital discharge plus a 30-day prescription for oral naltrexone, or (2) a single 380 mg intramuscular injection of naltrexone administered prior to discharge and a second injection one month later. The central hypothesis is that hospital-administered injectable naltrexone, when compared to daily oral naltrexone taken at home, will reduce alcohol use in the days immediately following hospitalization. Injectable naltrexone has been efficacious vs. placebo in addition to behavioral treatment in several studies. However, it has yet to be examined in head-to-head comparison with oral naltrexone, or in the hospital setting as an intervention that might facilitate behavioral treatment follow up after discharge.

Detailed Description
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The proposed project is a pilot feasibility study of inpatient veterans with problem alcohol use at the William S. Middleton VA Hospital. The over-arching goal is to understand the impact of medication adherence upon engagement in behavioral treatment for alcohol use disorders. Participants will be randomized to one of two parallel study conditions: (1) an initial 50 mg oral dose of naltrexone prior to hospital discharge plus a 30-day prescription for oral naltrexone, or (2) a single 380 mg intramuscular injection of naltrexone (duration of action = 30 days) administered prior to discharge followed by a second injection one month later. The central hypothesis is that hospital-administered, long-acting injectable naltrexone, when compared to daily oral naltrexone, will reduce alcohol use in the days immediately following hospitalization. This reduced consumption, we hypothesize, will be followed by improved engagement in substance abuse treatment. Primary Aim: Demonstrate the feasibility of the proposed recruitment methods and study design. This aim comprises two measures with corresponding goals: (1) Recruitment/enrollment-with a recruitment goal of 50 eligible and consenting subjects in an 8 month time period, and (2) Follow-up data collection with a goal of post-hospitalization follow-up data on no less than 70% of enrolled subjects. Secondary Aims: As a pilot feasibility study, we may not anticipate sufficient power to attain statistical significance on patient-oriented outcome measures. However, it will be important for us to consider and to evaluate pertinent outcomes and potential moderators in order to (1) develop and fine-tune study design, and (2) determine effect sizes for primary outcomes so that we may calculate appropriate sample sizes for future larger study. As such, the secondary aims for the current study are: To compare injectable naltrexone study to oral naltrexone in terms of attendance to recommended outpatient substance abuse treatment. We hypothesize that injectable naltrexone will be associated with improved likelihood of attending initial visits for substance abuse treatment. To compare study arms in terms of ongoing alcohol consumption. We hypothesize that (1) improved medication adherence in the oral naltrexone arm and (2) assignment to injectable naltrexone will be associated with reduced alcohol consumption (number of heavy drinking days in the past 14 days) following hospital discharge.

Official Title
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Pharmacotherapeutic Intervention to Improve Treatment Engagement Among Alcohol-dependent Veterans After Hospital Discharge

Conditions
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Alcohol Dependence

Intervention / Treatment
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* Drug: Naltrexone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older diagnostic criteria for alcohol dependence or abuse women of childbearing potential who have a negative screening urine pregnancy test and are willing to use reliable birth control methods throughout the duration of the study Exclusion Criteria: active or recently active (less than 1 year) opioid dependence or daily use of opioid analgesics acute hepatitis or liver failure pregnancy women who are currently breastfeeding active suicidality inability to provide written informed consent as determined by study comprehension questions

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: oral naltrexone<br>an initial 50 mg oral dose of naltrexone prior to hospital discharge plus a 30-day prescription for oral naltrexone | Drug: Naltrexone<br>* Naltexone was chosen for this study because naltrexone is the only medication available in both oral daily and injectable monthly formulations, which will allow the study to examine issues around medication adherence.<br>* Other names: Revia, Vivitrol;|
| Experimental: injectable naltrexone<br>a single 380 mg intramuscular injection of naltrexone (duration of action = 30 days)prior to hospital discharge followed by a second injection one month later. | Drug: Naltrexone<br>* Naltexone was chosen for this study because naltrexone is the only medication available in both oral daily and injectable monthly formulations, which will allow the study to examine issues around medication adherence.<br>* Other names: Revia, Vivitrol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Retention Rate: Percentage of Participants Attended an Initial Behavioral Treatment Visit Within 2 Weeks of Hospital Discharge. | Retention rate was measured in terms of percentage of participants attended an initial behavioral treatment visit within 2 weeks of hospital discharge. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Attended Recommended Outpatient Substance Abuse Treatment | Attendance to recommended outpatient substance abuse treatment will be compared between injectable naltrexone group and oral naltrexone group. Keeping patients engaged in treatment is desirable and is known to improve addiction-related outcomes. | 12 months | 
| Percentage of Participants Adhered to Medication | Medication adherence was measured as percentage of participants who took ≥ 80% of daily naltrexone doses determined via pill counts. Adherence of daily medication will predict treatment engagement following hospital discharge. | 12 months | 
| Ongoing Alcohol Consumption | To compare study arms in terms of ongoing alcohol consumption. We hypothesize that (1) improved medication adherence in the oral naltrexone arm and (2) assignment to injectable naltrexone will be associated with reduced alcohol consumption (number of heavy drinking days in the past 14 days) following hospital discharge. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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alcohol, veterans