Managing Alcoholism in People Who Do Not Respond to Naltrexone (EXTEND)
August 28, 2019 updated by: David Oslin, University of Pennsylvania
Non-Response to Naltrexone (NTX): Next Steps in Managing Alcoholism
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.
Study Overview
Status
Completed
Conditions
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.
Study Type
Interventional
Enrollment (Actual)
302
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- University of Pennsylvania Treatment Research Center, Chestnut Street
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Phase 1 Liberal Response
From the start of baseline subjects were randomly assigned to this arm which defined relapse/non-responder as having 5 or heavy drinking days in the first 8 weeks of treatment otherwise the subject was considered a responder.
|
100mg/day, up to 8 weeks during Phase 1, 16 weeks in phase 2.
Other Names:
|
|
Experimental: Phase 1 Stringent Response
From the start of baseline subjects were randomly assigned to this arm which defined relapse/non-responder as having 2 or heavy drinking days in the first 8 weeks of treatment otherwise the subject was considered a responder.
|
100mg/day, up to 8 weeks during Phase 1, 16 weeks in phase 2.
Other Names:
|
|
Experimental: Phase 2 nalt and tele for responders
Phase 2: Naltrexone and telephone counseling for responders.
|
100mg/day, up to 8 weeks during Phase 1, 16 weeks in phase 2.
Other Names:
Bi-weekly telephone calls lasting 15-20 minutes focused on the same content as MM.
|
|
Experimental: Phase 2 nalt, MM and CBI for NR
Phase 2: naltrexone, Medication Management (MM) and Combined Behavioral Intervention (CBI) for non-responders (NR).
|
100mg/day, up to 8 weeks during Phase 1, 16 weeks in phase 2.
Other Names:
Brief manual-based therapy for up to 8 weeks during phase 1, 16 during phase 2.
Other Names:
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.
Other Names:
|
|
Placebo Comparator: Phase 2 placebo, MM and CBI for NR
Phase 2: placebo, Medication Management (MM) and Combined Behavioral Intervention (CBI) for non-responders (NR)
|
Brief manual-based therapy for up to 8 weeks during phase 1, 16 during phase 2.
Other Names:
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.
Other Names:
placebo comparer for 16 weeks in phase 2.
Other Names:
|
|
Experimental: Phase 2 naltrexone for responders
Phase 2: Naltrexone and TAU for phase 1 responders.
|
100mg/day, up to 8 weeks during Phase 1, 16 weeks in phase 2.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Count of Responders and Non-responders in Phase 1
Time Frame: 8 weeks
|
This is the number of patients who responded to phase 1 treatment based on the definition that subjects were randomly assigned to.
|
8 weeks
|
|
Percentage of Heavy Drinking Days
Time Frame: 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.
|
16 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: David W. Oslin, M.D., University of Pennsylvania
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
September 1, 2003
Primary Completion (Actual)
April 1, 2008
Study Completion (Actual)
July 1, 2008
Study Registration Dates
First Submitted
June 20, 2005
First Submitted That Met QC Criteria
June 20, 2005
First Posted (Estimate)
June 21, 2005
Study Record Updates
Last Update Posted (Actual)
September 18, 2019
Last Update Submitted That Met QC Criteria
August 28, 2019
Last Verified
August 1, 2019
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- NIAAAOSL014851, 708534
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
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