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Managing Alcoholism in People Who Do Not Respond to Naltrexone (EXTEND)

Primary Purpose

Alcoholism

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Naltrexone
placebo
Medication Management (MM)
Combined Behavioral Intervention (CBI)
Telephone Counseling
Sponsored by
University of Pennsylvania
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alcoholism focused on measuring Alcoholism, alcohol abuse, therapy, drug resistance, naltrexone, patient care management, human subject

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Pennsylvania Treatment Research Center, Chestnut Street

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Experimental

Arm Label

Phase 1 Liberal Response

Phase 1 Stringent Response

Phase 2 nalt and tele for responders

Phase 2 nalt, MM and CBI for NR

Phase 2 placebo, MM and CBI for NR

Phase 2 naltrexone for responders

Arm Description

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.

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.

Phase 2: Naltrexone and telephone counseling for responders.

Phase 2: naltrexone, Medication Management (MM) and Combined Behavioral Intervention (CBI) for non-responders (NR).

Phase 2: placebo, Medication Management (MM) and Combined Behavioral Intervention (CBI) for non-responders (NR)

Phase 2: Naltrexone and TAU for phase 1 responders.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Full Information

First Posted
June 20, 2005
Last Updated
August 28, 2019
Sponsor
University of Pennsylvania
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1. Study Identification

Unique Protocol Identification Number
NCT00115037
Brief Title
Managing Alcoholism in People Who Do Not Respond to Naltrexone
Acronym
EXTEND
Official Title
Non-Response to Naltrexone (NTX): Next Steps in Managing Alcoholism
Study Type
Interventional

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
September 2003 (undefined)
Primary Completion Date
April 2008 (Actual)
Study Completion Date
July 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Pennsylvania

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcoholism
Keywords
Alcoholism, alcohol abuse, therapy, drug resistance, naltrexone, patient care management, human subject

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
302 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase 1 Liberal Response
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 1 Stringent Response
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 2 nalt and tele for responders
Arm Type
Experimental
Arm Description
Phase 2: Naltrexone and telephone counseling for responders.
Arm Title
Phase 2 nalt, MM and CBI for NR
Arm Type
Experimental
Arm Description
Phase 2: naltrexone, Medication Management (MM) and Combined Behavioral Intervention (CBI) for non-responders (NR).
Arm Title
Phase 2 placebo, MM and CBI for NR
Arm Type
Placebo Comparator
Arm Description
Phase 2: placebo, Medication Management (MM) and Combined Behavioral Intervention (CBI) for non-responders (NR)
Arm Title
Phase 2 naltrexone for responders
Arm Type
Experimental
Arm Description
Phase 2: Naltrexone and TAU for phase 1 responders.
Intervention Type
Drug
Intervention Name(s)
Naltrexone
Other Intervention Name(s)
ReVia
Intervention Description
100mg/day, up to 8 weeks during Phase 1, 16 weeks in phase 2.
Intervention Type
Drug
Intervention Name(s)
placebo
Other Intervention Name(s)
placebo pill
Intervention Description
placebo comparer for 16 weeks in phase 2.
Intervention Type
Behavioral
Intervention Name(s)
Medication Management (MM)
Other Intervention Name(s)
MM
Intervention Description
Brief manual-based therapy for up to 8 weeks during phase 1, 16 during phase 2.
Intervention Type
Behavioral
Intervention Name(s)
Combined Behavioral Intervention (CBI)
Other Intervention Name(s)
CBI
Intervention Description
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.
Intervention Type
Behavioral
Intervention Name(s)
Telephone Counseling
Intervention Description
Bi-weekly telephone calls lasting 15-20 minutes focused on the same content as MM.
Primary Outcome Measure Information:
Title
Count of Responders and Non-responders in Phase 1
Description
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
Title
Percentage of Heavy Drinking Days
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David W. Oslin, M.D.
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pennsylvania Treatment Research Center, Chestnut Street
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
20716308
Citation
Chakravorty S, Kuna ST, Zaharakis N, O'Brien CP, Kampman KM, Oslin D. Covariates of craving in actively drinking alcoholics. Am J Addict. 2010 Sep-Oct;19(5):450-7. doi: 10.1111/j.1521-0391.2010.00067.x.
Results Reference
derived

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Managing Alcoholism in People Who Do Not Respond to Naltrexone

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