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

This study has been completed.
Sponsor:
Information provided by:
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT00115037
First received: June 20, 2005
Last updated: August 4, 2011
Last verified: August 2011
  Purpose

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.


Condition Intervention Phase
Alcoholism
Drug: Naltrexone
Drug: placebo
Behavioral: Medical Management (MM)
Behavioral: Combined Behavioral Intervention (CBI)
Behavioral: Telephone Counseling
Other: Treatment as Usual (TAU)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Non-Response to Naltrexone (NTX): Next Steps in Managing Alcoholism

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • Reduction in alcohol use for subjects treated with a combination of CBI and NTX compared to CBI and placebo in those subjects who failed to respond to MM and NTX. [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Enrollment: 302
Study Start Date: September 2003
Study Completion Date: July 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: P1
In phase 1, all participants on open-label naltrexone with MM.
Drug: Naltrexone
100mg/day, up to 8 weeks during Phase 1, 16 weeks in phase 2.
Other Name: ReVia
Behavioral: Medical Management (MM)
Brief manual-based therapy for up to 8 weeks during phase 1, 16 during phase 2.
Other Name: MM
Experimental: P2RA
Phase 2: Naltrexone and TAU for phase 1 responders.
Drug: Naltrexone
100mg/day, up to 8 weeks during Phase 1, 16 weeks in phase 2.
Other Name: ReVia
Other: Treatment as Usual (TAU)
Responders are informed of the benefits of continued treatment with naltrexone and are given a four week supply of medication as well as a prescription for 3 months.
Experimental: P2RB
Phase 2: Naltrexone and telephone counseling for phase 1 responders.
Drug: Naltrexone
100mg/day, up to 8 weeks during Phase 1, 16 weeks in phase 2.
Other Name: ReVia
Behavioral: Telephone Counseling
Bi-weekly telephone calls lasting 15-20 minutes focused on the same content as MM.
Experimental: P2NA
Phase 2: naltrexone, MM and CBI for phase 1 non-responders.
Drug: Naltrexone
100mg/day, up to 8 weeks during Phase 1, 16 weeks in phase 2.
Other Name: ReVia
Behavioral: Medical Management (MM)
Brief manual-based therapy for up to 8 weeks during phase 1, 16 during phase 2.
Other Name: MM
Behavioral: Combined 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.
Other Name: CBI
Placebo Comparator: P2NB
Phase 2: placebo, MM and CBI for phase 1 non-responders.
Drug: placebo
placebo comparer for 16 weeks in phase 2.
Behavioral: Medical Management (MM)
Brief manual-based therapy for up to 8 weeks during phase 1, 16 during phase 2.
Other Name: MM
Behavioral: Combined 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.
Other Name: CBI

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00115037

Locations
United States, Pennsylvania
University of Pennsylvania Treatment Research Center, Chestnut Street
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
Investigators
Principal Investigator: David W. Oslin, M.D. University of Pennsylvania
  More Information

No publications provided by University of Pennsylvania

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: David Oslin, M.D., University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00115037     History of Changes
Other Study ID Numbers: NIAAAOSL014851
Study First Received: June 20, 2005
Last Updated: August 4, 2011
Health Authority: United States: Federal Government

Keywords provided by University of Pennsylvania:
Alcoholism
alcohol abuse
therapy
drug resistance
naltrexone
patient care management
human subject

Additional relevant MeSH terms:
Alcoholism
Alcohol-Related Disorders
Substance-Related Disorders
Mental Disorders
Naltrexone
Narcotic Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 28, 2014