Alcohol DependencePhase 4NCT00831272
Pharmacogenetic Response to Naltrexone For Alcohol Dependence
A Phase 4 study testing naltrexone in people with Alcohol Dependence, run by David Oslin at 4 sites in United States.
Trial summary
The aims of the study are to test for treatment outcome differences in alcohol dependent subjects randomly assigned to 12 weeks of treatment with NTX (50mg/day) or placebo among those with one or two copies of the Asp40 allele of the mu-opioid receptor compared to those homozygous for the Asn40 allele. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Alcohol Dependence
- What is being tested?
- naltrexone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 221 participants
- Where
- 4 sitesUnited States
- Study dates
- 5 Jan 2009to 15 Jan 2014
- 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
- Participant is male or female, 18 years of age or older, and of European or Asian descent.
- Participant has a current DSM-IV diagnosis of alcohol dependence using the SCID/MINI.
- The participant has signed a witnessed informed consent form.
- Participant meets the following drinking criteria as measured by the Timeline Follow Back (TLFB): a. Drinks at least an average of 21 drinks/wk in the 60-day period prior to intake and b. Has 2 or more days of heavy drinking (defined as 5 or more drinks per day in males, 4 or more in females) in this same pre-treatment period.
- Participant has at least 48 hours of abstinence, as determined by subject report and breathalyzer measure immediately prior to randomization.
- Participant scores below 8 on the Clinical Inventory of Withdrawal from Alcohol (CIWA) prior to starting Naltrexone.
- Participant has adequate vision, hearing and ability to communicate to allow study participation.
- Participant is able to speak, print and understand English.
Who cannot join
- Participant meets DSM-IV criteria for dependence on any substance other than alcohol or nicotine in the last 6 months.
- Participant has tested positive on the urine drug screen for opioids, benzodiazepines, or cocaine at the screening visit. Presence of THC is allowable.
- Participant has a current or lifetime DSM-IV diagnosis of bipolar affective disorder, schizophrenia, or any psychotic disorder.
- Participant has presence of unstable or serious medical illness such as a recent stroke, idiopathic seizure disorder, or cardiac disease.
- Participant has severe liver disease (SGPT (ALT) or SGOT (AST) of at least 3 times normal value at the time of randomization or an elevated Total Bilirubin level without evidence of Gilbert's Syndrome.
- Participant has taken any psychotropic medications (including disulfiram) regularly within the last seven days (14 for fluoxetine) prior to randomization or needs immediate treatment with a psychotropic medication (antidepressant, antipsychotic, benzodiazepine, or mood stabilizing medication). EXCEPTIONS: Zolpidem and ramelteon used sparingly if necessary for sleep; Oxazepam for alcohol detoxification; Seizure disorder medications.
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- Participant is over the age of 64 and has evidence of severe cognitive impairment as evidenced by a Mini-mental status exam (MMSE) score < 24.
- Participant meets DSM-IV criteria for current major depression (non-substance induced), PTSD, or panic disorder.
- Participant has suicidal or homicidal ideation necessitating inpatient hospitalization.
- Participant is a pre-menopausal female who is pregnant, nursing, or not using a reliable method of contraception.
- Participant is over age 64 and has evidence of severe cognitive impairment as evidenced by a Mini-mental status exam (MMSE) score less than 20.12. Participant is of African descent.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Geisinger Medical Center
Danville, Pennsylvania, 17822
Philadelphia VA Medical Center
Philadelphia, Pennsylvania, 19104
University of Pennsylvania Treatment Research Center
Philadelphia, Pennsylvania, 19104
VA Pittsburgh Healthcare System
Pittsburgh, Pennsylvania, 15206
About this study
Official title: Pharmacogenetic Response to Naltrexone for Alcohol Dependence
The aims of the study are to test for treatment outcome differences in alcohol dependent subjects randomly assigned to 12 weeks of treatment with NTX (50mg/day) or placebo among those with one or two copies of the Asp40 allele of the mu-opioid receptor compared to those homozygous for the Asn40 allele. Thus, the design of the study is a 2X2 cell double-blind randomization to NTX or placebo stratified by genotype. To meet these aims, 150 alcohol dependent outpatients with one or two copies of the Asp40 variant of the mu-opioid receptor and 190 subjects homozygous for the Asn40 variant will be recruited across the four participating sites.
Read the detailed description
Despite the well established efficacy of naltrexone, there are significant variations in individual responses to naltrexone. A critical question remains: under what circumstances and for which patients will naltrexone (NTX) be most beneficial? Recent work at our center provides evidence that the mu-opioid receptor (OPRM1) gene polymorphism A118G (Asn40Asp) imparts a significant change in treatment response. We have shown that patients with 1-2 copies of the Asp40 variant have significantly better treatment responses than patients with Asn40 variant (absence of heavy drinking -73.9% v/s 49% response). To further consolidate our knowledge, we wish to test the relationship between A118G polymorphism and the response to treatment with naltrexone. This work is focused on subjects of European or Asian descent as the A118G polymorphism occurs in less than 1% of those of African descent.
The study consists of 12 weeks of outpatient treatment with 50mg/day of naltrexone or placebo. Up to 340 subjects will be recruited across four sites. The inclusion criteria include adult males and females of European or Asian descent with DSM-IV diagnosis of alcohol dependence and heavy drinking per TLFB criteria. Patients with major psychiatric disorders or on psychotropic medications, other substance dependence problems (except nicotine), severe cognitive impairment, active suicidal/homicidal thoughts and serious medical conditions (including liver disorders) will be excluded.
The ultimate aim of this line of investigation is to further establish a genetic link between alcohol dependence and treatment by defining an endophenotype associated with treatment response.
Based upon these very promising findings, the aim of this study is to examine prospectively the interaction between a functional polymorphism of the mu-opioid receptor (A+118G (Asn40Asp)) and response to treatment with naltrexone. A secondary aim of this study is to examine the role of the Asp40 allele in alternating the subjective effects from alcohol use in alcohol dependent individuals that have been demonstrated in human laboratory experiments.
We hypothesize that naltrexone - but not placebo - will produce a greater clinical response during the 12 weeks of the trial in subjects with one or two copies of the Asp40 variant ("Asp40 positives") than in subjects homozygous for the Asn40 allele. Response to naltrexone will be measured by a reduction in the number of heavy drinking days (as defined by >5 drinks/day for males; >4 for females) during the 12 weeks of the trial.
We also expect that there will be an interaction between medication and genotype such that, as compared to the groups on placebo or homozygous for Asn40, Asp40 positive subjects randomized to naltrexone will report less "high" from alcohol consumption (on the Biphasic Alcohol Effects Scale), and the lowest levels of alcohol craving over time (on the Penn Alcohol Craving Scale).
- Conditions
- Alcohol Dependence
- Being tested
- naltrexone, Placebo
- 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
50mg/day
PlaceboDrug
Also called sugar pill
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Naltrexone | Experimental | 50mg/day of naltrexone Receives: Drug: naltrexone |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Response to Naltrexone, as Measured by a Reduction in the Percent Days of Heavy Drinking Days (as Defined by >5 Drinks/Day for Males; >4 for Females) During the 12 Weeks of the Trial.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2009 (estimated)
- Study start5 Jan 2009
- Primary completion20 Dec 2013
- Study completion15 Jan 2014
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 Alcohol DependenceStudies of the same condition, open and under way.
- 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
- 221 participants (actual)
Sponsor and investigators
- Lead sponsor
- David Oslin
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Responsible party
- Sponsor-investigator, David Oslin, University of Pennsylvania
- Investigators
- David Oslin, MD, Principal investigator, University of Pennsylvania/ Philadelphia VA Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00831272
- Sponsor's protocol ID
- 807991
- Other IDs
- 5R01AA017164-05
- Status last verified
- Mar 2017
- First submitted
- 26 Jan 2009
- Last updated
- 11 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Oslin DW, Leong SH, Lynch KG, Berrettini W, O'Brien CP, Gordon AJ, Rukstalis M. Naltrexone vs Placebo for the Treatment of Alcohol Dependence: A Randomized Clinical Trial. JAMA Psychiatry. 2015 May;72(5):430-7. doi: 10.1001/jamapsychiatry.2014.3053.
PubMed 25760804
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacogenetic Response to Naltrexone for Alcohol Dependence
- ClinicalTrials.gov ID
- NCT00831272
- Acronym / sponsor ID
- 807991
- Conditions
- Alcohol Dependence
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 221 participants (actual)
- Lead sponsor
- David OslinUniversity, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Study start
- 5 Jan 2009 (actual)
- Primary completion
- 20 Dec 2013 (actual)
- Study completion
- 15 Jan 2014 (actual)
- First posted
- 28 Jan 2009 (estimated)
- Results
- Posted 11 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aims of the study are to test for treatment outcome differences in alcohol dependent subjects randomly assigned to 12 weeks of treatment with NTX (50mg/day) or placebo among those with one or two copies of the Asp40 allele of the mu-opioid receptor compared to those homozygous for the Asn40 allele. Thus, the design of the study is a 2X2 cell double-blind randomization to NTX or placebo stratified by genotype. To meet these aims, 150 alcohol dependent outpatients with one or two copies of the Asp40 variant of the mu-opioid receptor and 190 subjects homozygous for the Asn40 variant will be recruited across the four participating sites.
Detailed description
Despite the well established efficacy of naltrexone, there are significant variations in individual responses to naltrexone. A critical question remains: under what circumstances and for which patients will naltrexone (NTX) be most beneficial? Recent work at our center provides evidence that the mu-opioid receptor (OPRM1) gene polymorphism A118G (Asn40Asp) imparts a significant change in treatment response. We have shown that patients with 1-2 copies of the Asp40 variant have significantly better treatment responses than patients with Asn40 variant (absence of heavy drinking -73.9% v/s 49% response). To further consolidate our knowledge, we wish to test the relationship between A118G polymorphism and the response to treatment with naltrexone. This work is focused on subjects of European or Asian descent as the A118G polymorphism occurs in less than 1% of those of African descent.
The study consists of 12 weeks of outpatient treatment with 50mg/day of naltrexone or placebo. Up to 340 subjects will be recruited across four sites. The inclusion criteria include adult males and females of European or Asian descent with DSM-IV diagnosis of alcohol dependence and heavy drinking per TLFB criteria. Patients with major psychiatric disorders or on psychotropic medications, other substance dependence problems (except nicotine), severe cognitive impairment, active suicidal/homicidal thoughts and serious medical conditions (including liver disorders) will be excluded.
The ultimate aim of this line of investigation is to further establish a genetic link between alcohol dependence and treatment by defining an endophenotype associated with treatment response.
Based upon these very promising findings, the aim of this study is to examine prospectively the interaction between a functional polymorphism of the mu-opioid receptor (A+118G (Asn40Asp)) and response to treatment with naltrexone. A secondary aim of this study is to examine the role of the Asp40 allele in alternating the subjective effects from alcohol use in alcohol dependent individuals that have been demonstrated in human laboratory experiments.
We hypothesize that naltrexone - but not placebo - will produce a greater clinical response during the 12 weeks of the trial in subjects with one or two copies of the Asp40 variant ("Asp40 positives") than in subjects homozygous for the Asn40 allele. Response to naltrexone will be measured by a reduction in the number of heavy drinking days (as defined by >5 drinks/day for males; >4 for females) during the 12 weeks of the trial.
We also expect that there will be an interaction between medication and genotype such that, as compared to the groups on placebo or homozygous for Asn40, Asp40 positive subjects randomized to naltrexone will report less "high" from alcohol consumption (on the Biphasic Alcohol Effects Scale), and the lowest levels of alcohol craving over time (on the Penn Alcohol Craving Scale).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Naltrexone | Experimental | Drug: naltrexone50mg/day of naltrexone |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Participant is male or female, 18 years of age or older, and of European or Asian descent.
- Participant has a current DSM-IV diagnosis of alcohol dependence using the SCID/MINI.
- The participant has signed a witnessed informed consent form.
- Participant meets the following drinking criteria as measured by the Timeline Follow Back (TLFB): a. Drinks at least an average of 21 drinks/wk in the 60-day period prior to intake and b. Has 2 or more days of heavy drinking (defined as 5 or more drinks per day in males, 4 or more in females) in this same pre-treatment period.
- Participant has at least 48 hours of abstinence, as determined by subject report and breathalyzer measure immediately prior to randomization.
Key exclusion criteria (11 listed)
- Participant meets DSM-IV criteria for dependence on any substance other than alcohol or nicotine in the last 6 months.
- Participant has tested positive on the urine drug screen for opioids, benzodiazepines, or cocaine at the screening visit. Presence of THC is allowable.
- Participant has a current or lifetime DSM-IV diagnosis of bipolar affective disorder, schizophrenia, or any psychotic disorder.
- Participant has presence of unstable or serious medical illness such as a recent stroke, idiopathic seizure disorder, or cardiac disease.
- Participant has severe liver disease (SGPT (ALT) or SGOT (AST) of at least 3 times normal value at the time of randomization or an elevated Total Bilirubin level without evidence of Gilbert's Syndrome.
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: ReVia50mg/day | Drug | Naltrexone |
| PlaceboAlso: sugar pillPlacebo | Drug | Placebo |
Primary outcome
Clinical Response to Naltrexone, as Measured by a Reduction in the Percent Days of Heavy Drinking Days (as Defined by >5 Drinks/Day for Males; >4 for Females) During the 12 Weeks of the Trial.
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 25760804Oslin DW, Leong SH, Lynch KG, Berrettini W, O'Brien CP, Gordon AJ, Rukstalis M. Naltrexone vs Placebo for the Treatment of Alcohol Dependence: A Randomized Clinical Trial. JAMA Psychiatry. 2015 May;72(5):430-7. doi: 10.1001/jamapsychiatry.2014.3053.
- 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 Oslin, MD principal investigator
University of Pennsylvania/ Philadelphia VA Medical Center
4 sites 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 in people with Alcohol Dependence, run by David Oslin at 4 sites 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 8 inclusion and 11 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 11 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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 11 May 2017). 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?
Clinical Response to Naltrexone, as Measured by a Reduction in the Percent Days of Heavy Drinking Days (as Defined by >5 Drinks/Day for Males; >4 for Females) During the 12 Weeks of the Trial. (time frame: 12 weeks). 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 NCT00831272, 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 11 May 2017.