CompletedNCT00115037EXTENDUpdated Sep 18, 2019Results posted

Managing Alcoholism in People Who Do Not Respond to Naltrexone

A Phase 4 interventional study of Naltrexone and placebo in Alcoholism, sponsored by University of Pennsylvania. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-09-18.

Sponsored by University of Pennsylvania · Phase 4, Interventional, and Treatment

Phase: Phase 4
Study type: Interventional
Enrollment: 302
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study 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.

Read the 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.

Conditions studied

Alcoholism

Browse trials for

Alcoholism 1,606

Keywords

Alcoholism
alcohol abuse
therapy
drug resistance
naltrexone
patient care management
human subject

In context

Alcoholism

1,606 studies on the registry are indexed under Alcoholism; 329 are open to participants now.

This study's enrollment of 302 is above the median of 87 across 1,371 interventional studies indexed under Alcoholism.

Browse Alcoholism studies →

Lead sponsor

University of Pennsylvania is the lead sponsor of 1,635 studies on the registry; 239 are open to participants now.

Of its 154 completed or terminated interventional studies of FDA-regulated products, 104 (68%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

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

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 design

Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 302 participants (actual)

Study arms

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.
Drug: Naltrexone
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.
Drug: Naltrexone
Experimental
Phase 2 nalt and tele for responders
Phase 2: Naltrexone and telephone counseling for responders.
Drug: Naltrexone · Behavioral: Telephone Counseling
Experimental
Phase 2 nalt, MM and CBI for NR
Phase 2: naltrexone, Medication Management (MM) and Combined Behavioral Intervention (CBI) for non-responders (NR).
Drug: Naltrexone · Behavioral: Medication Management (MM) · Behavioral: Combined Behavioral Intervention (CBI)
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)
Drug: placebo · Behavioral: Medication Management (MM) · Behavioral: Combined Behavioral Intervention (CBI)
Experimental
Phase 2 naltrexone for responders
Phase 2: Naltrexone and TAU for phase 1 responders.
Drug: Naltrexone

Interventions

DrugNaltrexone
100mg/day, up to 8 weeks during Phase 1, 16 weeks in phase 2.
Also known as: ReVia
Drugplacebo
placebo comparer for 16 weeks in phase 2.
Also known as: placebo pill
BehavioralMedication Management (MM)
Brief manual-based therapy for up to 8 weeks during phase 1, 16 during phase 2.
Also known as: MM
BehavioralCombined 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.
Also known as: CBI
BehavioralTelephone Counseling
Bi-weekly telephone calls lasting 15-20 minutes focused on the same content as MM.

What researchers measure

Primary outcomes

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.
Time frame: 8 weeks
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.
Time frame: 16 weeks

Results

Posted Sep 18, 2019

Limitations and caveats

Overall the sample size was limited for detecting results in the second phase.

Participant flow

Study participants were recruited through advertisements in the local media, referrals from physicians, or self referrals.

Phase1

Participant flow — Phase1
Milestone	Phase1: Liberal	Phase1: Stringent
Started	152	150
Completed	127	123
Not completed	25	27
Withdrew: Lost to follow-up	16	23
Withdrew: Withdrawal by subject	9	4

Phase2

Participant flow — Phase2
Milestone	Phase2: Responder - Naltx (Usual Care)	Phase2: Responder - Naltx+Phone (TDM)	Phase2: Non-responder - Naltx, MM and CBI	Phase2: Non-responder - Placebo, MM and CBI
Started	91	92	34	33
Completed	76	77	28	21
Not completed	15	15	6	12
Withdrew: Death	1	0	0	1
Withdrew: Withdrawal by subject	2	1	2	1
Withdrew: Lost to follow-up	12	14	4	10

Outcome measures

PrimaryCount 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.

Time frame:: 8 weeks
Reported as:: Count of participants · Participants

Count of Responders and Non-responders in Phase 1
Participants	Phase 1 Liberal Response	Phase 1 Stringent Response
Count of Responders and Non-responders in Phase 1	103	80

PrimaryPercentage 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.

Time frame:: 16 weeks
Reported as:: Median · percentage days of heavy drinking

Percentage of Heavy Drinking Days
percentage days of heavy drinking	Phase 2 Naltrexone for Responders	Phase 2 Nalt and Tele for Responders	Phase 2 Nalt, MM and CBI for NR	Phase 2 Placebo, MM and CBI for NR
Percentage of Heavy Drinking Days	0 (0 to 4.8)	0 (0 to 3.2)	27.7 (2.8 to 61.6)	17.8 (0 to 58.7)

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Phase1: Liberal	0/152 (0%)	0/152 (0%)	0/152 (0%)
Phase1: Stringent	0/150 (0%)	0/150 (0%)	0/150 (0%)
Phase2: Responder - Naltx (Usual Care)	1/91 (1.1%)	0/91 (0%)	0/91 (0%)
Phase2: Responder - Naltx+Phone (TDM)	0/92 (0%)	0/92 (0%)	0/92 (0%)
Phase2: Non-responder - Naltx, MM and CBI	0/34 (0%)	0/34 (0%)	0/34 (0%)
Phase2: Non-responder - Placebo, MM and CBI	1/33 (3%)	0/33 (0%)	0/33 (0%)

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Phase1: Liberal	Phase1: Stringent	Total
Age	48.70 ± 10.40	48.49 ± 10.36	48.6 ± 10.4

Sex: Female, Male
Sex: Female, Male(Participants)	Phase1: Liberal	Phase1: Stringent	Total
Female	22	20	42
Male	130	130	260

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Phase1: Liberal	Phase1: Stringent	Total
Hispanic or Latino	6	4	10
Not Hispanic or Latino	146	146	292
Unknown or Not Reported	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Phase1: Liberal	Phase1: Stringent	Total
American Indian or Alaska Native	0	1	1
Asian	1	1	2
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	40	45	85
White	111	103	214
More than one race	0	0	0
Unknown or Not Reported	0	0	0

Study locations

1 site

University of Pennsylvania Treatment Research Center, Chestnut Street
Philadelphia, Pennsylvania 19104, United States

References and documents

Publications

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. PubMed 20716308 ↗

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Sep 18, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00115037
Lead sponsor: University of Pennsylvania
Responsible party: David Oslin (Professor, University of Pennsylvania) — Principal investigator
First posted: Jun 21, 2005
Start date: Sep 2003
Primary completion: Apr 2008
Completion: Jul 2008
Results posted: Sep 18, 2019
Last update: Sep 18, 2019

Study contacts

David W. Oslin, M.D.

principal investigator · University of Pennsylvania

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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