AlcoholismPhase 4EXTENDNCT00115037
Managing Alcoholism in People Who Do Not Respond to Naltrexone
A Phase 4 study testing Naltrexone, Medication Management (MM) and Combined Behavioral Intervention (CBI) in people with Alcoholism, run by University of Pennsylvania at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Alcoholism
- What is being tested?
- Naltrexone, Medication Management (MM) and Combined Behavioral Intervention (CBI)
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 302 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2003to Jul 2008
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania Treatment Research Center, Chestnut Street
Philadelphia, Pennsylvania, 19104
About this study
Official title: 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.
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
- Alcoholism
- Being tested
- Naltrexone, placebo, Medication Management (MM), Combined Behavioral Intervention (CBI), Telephone Counseling
- Keywords
- Alcoholism, alcohol abuse, therapy, drug resistance, naltrexone, patient care management, human subject
- Medical subject headings
- Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NaltrexoneDrug
Also called ReVia
100mg/day, up to 8 weeks during Phase 1, 16 weeks in phase 2.
placeboDrug
Also called placebo pill
placebo comparer for 16 weeks in phase 2.
Medication Management (MM)Behavioural
Also called MM
Brief manual-based therapy for up to 8 weeks during phase 1, 16 during phase 2.
Combined Behavioral Intervention (CBI)Behavioural
Also called 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.
Telephone CounselingBehavioural
Bi-weekly telephone calls lasting 15-20 minutes focused on the same content as MM.
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 Liberal Response | Experimental | 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. Receives: Drug: Naltrexone |
| Phase 1 Stringent Response | Experimental | 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. Receives: Drug: Naltrexone |
| Phase 2 nalt and tele for responders | Experimental | Phase 2: Naltrexone and telephone counseling for responders. Receives: Drug: Naltrexone; Behavioral: Telephone Counseling |
| Phase 2 nalt, MM and CBI for NR | Experimental | Phase 2: naltrexone, Medication Management (MM) and Combined Behavioral Intervention (CBI) for non-responders (NR). Receives: Drug: Naltrexone; Behavioral: Medication Management (MM); Behavioral: Combined Behavioral Intervention (CBI) |
| Phase 2 placebo, MM and CBI for NR | Placebo comparator | Phase 2: placebo, Medication Management (MM) and Combined Behavioral Intervention (CBI) for non-responders (NR) Receives: Drug: placebo; Behavioral: Medication Management (MM); Behavioral: Combined Behavioral Intervention (CBI) |
| Phase 2 naltrexone for responders | Experimental | Phase 2: Naltrexone and TAU for phase 1 responders. Receives: Drug: Naltrexone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2005 (estimated)
- Study startSep 2003
- Primary completionApr 2008
- Study completionJul 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AlcoholismStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 302 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Oslin, University of Pennsylvania
- Investigators
- David W. Oslin, M.D., Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00115037
- Sponsor's protocol ID
- NIAAAOSL014851, 708534
- Acronym
- EXTEND
- Status last verified
- Aug 2019
- First submitted
- 20 Jun 2005
- Last updated
- 18 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
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
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-Response to Naltrexone (NTX): Next Steps in Managing Alcoholism
- ClinicalTrials.gov ID
- NCT00115037
- Acronym / sponsor ID
- EXTEND / NIAAAOSL014851, 708534
- Conditions
- Alcoholism
- Keywords
- Alcoholism, alcohol abuse, therapy, drug resistance, naltrexone, patient care management, human subject
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 302 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- Sep 2003
- Primary completion
- Apr 2008 (actual)
- Study completion
- Jul 2008 (actual)
- First posted
- 21 Jun 2005 (estimated)
- Results
- Posted 18 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Phase 1 Liberal Response | Experimental | Drug: NaltrexoneFrom 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. |
| Phase 1 Stringent Response | Experimental | Drug: NaltrexoneFrom 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 nalt and tele for responders | Experimental | Drug: Naltrexone, Behavioral: Telephone CounselingPhase 2: Naltrexone and telephone counseling for responders. |
| Phase 2 nalt, MM and CBI for NR | Experimental | Drug: Naltrexone, Behavioral: Medication Management (MM), Behavioral: Combined Behavioral Intervention (CBI)Phase 2: naltrexone, Medication Management (MM) and Combined Behavioral Intervention (CBI) for non-responders (NR). |
| Phase 2 placebo, MM and CBI for NR | Placebo comparator | Drug: placebo, Behavioral: Medication Management (MM), Behavioral: Combined Behavioral Intervention (CBI)Phase 2: placebo, Medication Management (MM) and Combined Behavioral Intervention (CBI) for non-responders (NR) |
| Phase 2 naltrexone for responders | Experimental | Drug: NaltrexonePhase 2: Naltrexone and TAU for phase 1 responders. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NaltrexoneAlso: ReVia100mg/day, up to 8 weeks during Phase 1, 16 weeks in phase 2. | Drug | 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 naltrexone for responders |
| placeboAlso: placebo pillplacebo comparer for 16 weeks in phase 2. | Drug | Phase 2 placebo, MM and CBI for NR |
| Medication Management (MM)Also: MMBrief manual-based therapy for up to 8 weeks during phase 1, 16 during phase 2. | Behavioural | Phase 2 nalt, MM and CBI for NR, Phase 2 placebo, MM and CBI for NR |
| Combined Behavioral Intervention (CBI)Also: CBI45-60 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. | Behavioural | Phase 2 nalt, MM and CBI for NR, Phase 2 placebo, MM and CBI for NR |
| Telephone CounselingBi-weekly telephone calls lasting 15-20 minutes focused on the same content as MM. | Behavioural | Phase 2 nalt and tele for responders |
Primary outcome
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 20716308Chakravorty 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David W. Oslin, M.D. principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Naltrexone, Medication Management (MM) and Combined Behavioral Intervention (CBI) in people with Alcoholism, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Count of Responders and Non-responders in Phase 1 (time frame: 8 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00115037, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2019.