Alcohol Use DisorderPAUSENCT03864146
Pioglitazone for the Treatment of Alcohol Use Disorder
A study testing Brief Behavioral Compliance Enhancement Treatment in people with Alcohol Use Disorder, run by VA Office of Research and Development at 2 sites in United States.
Trial summary
Alcohol Use Disorder (AUD) is common among Veterans but medication treatment is used infrequently and the impact of these treatments are small to moderate at best. Pioglitazone, a medication FDA approved for diabetes, has been shown in pre-clinical studies to reduce alcohol. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Alcohol Use Disorder
- What is being tested?
- Brief Behavioral Compliance Enhancement Treatment
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 201 participants
- Where
- 2 sitesUnited States
- Study dates
- 17 Jul 2019to 29 Mar 2024
- Phase
- Interventional
- 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
- DSM-5 diagnosis of at least moderate alcohol use disorder using the SCID
- A mean of six heavy drinking days per month for the 3-months prior to baseline.
- Drinking at least 14 drinks for men or 7 drinks for women, or more per week for the 4 weeks preceding the screening visit.
- Willingness to provide contact information to confirm study follow-up appointments
- Ability to perform informed consent
- Female subjects: a negative pregnancy test
- Serum ALT < 3 times reference range
- Stable psychiatric medication doses the month prior to baseline visit (antidepressant, antipsychotic, subjects may have changes in trazodone for sleep)
Who cannot join
- Current DSM-5 diagnosis of moderate to severe psychoactive substance use disorder (i.e. cocaine, opiates, methamphetamine) other than cannabis or nicotine
- Medical conditions contraindicating pioglitazone pharmacotherapy (e.g., congestive heart failure, clinically significant edema, clinically significant liver disease, hypoglycemia, diabetes, history of bladder cancer)
- Taking medications known to have significant drug interactions with the study medication (CYP2C8 inhibitors or inducers, antihyperglycemic medications)
- Cognitive or physical impairment that precludes study participation
- Currently and seriously suicidal (i.e., plan and intent)
- Currently being treated for AUD with a medication (naltrexone, naltrexone injectable, acamprosate, topiramate, disulfiram and gabapentin)
Show all 10Show fewer
- Impending incarceration
- Pregnant or planning to become pregnant during the course of the trial or nursing for female patients
- Unwillingness to sign a written informed consent form
- Unwillingness to use a barrier method of birth control during the study for female patients
Trial locations and contacts
2 sites in 1 country.
United States2 sites
VA Long Beach Healthcare System, Long Beach, CA
Long Beach, California, 90822
Minneapolis VA Health Care System, Minneapolis, MN
Minneapolis, Minnesota, 55417-2309
About this study
Official title: A Randomized Trial of Pioglitazone for the Treatment of Alcohol Use Disorder
Alcohol Use Disorder (AUD) is common among Veterans but medication treatment is used infrequently and the impact of these treatments are small to moderate at best. Pioglitazone, a medication FDA approved for diabetes, has been shown in pre-clinical studies to reduce alcohol. The proposed study will test the efficacy of pioglitazone to reduce alcohol use in a double-blind placebo controlled trial. Investigators plan to compare pioglitazone to placebo in 200 Veterans who have an AUD and who are currently drinking alcohol at two Veterans Affairs Health Care Centers. The primary hypothesis is that Veterans with an AUD who are currently drinking alcohol will have a greater reduction in alcohol use following treatment with pioglitazone compared to those treated with placebo.
Read the detailed description
Background: Alcohol use disorder (AUD) and heavy drinking are common among Veterans with 42.2% of Veterans having a life-time history of AUD and 14.8% screening positive for past-year probable AUD. Although treatments for AUD have improved over the past several decades, more effective interventions are needed. Pioglitazone is an FDA approved medication used to treat diabetes. Pioglitazone is a PPAR agonist and has been reported to decrease voluntary alcohol consumption of a 10% alcohol solution in rats genetically selected for high alcohol consumption. In addition, when rats had to perform an operant task to receive alcohol, pioglitazone reduced alcohol self-administration but not saccharin intake. These data suggest that pioglitazone reduces the motivation to consume alcohol. No clinical studies of pioglitazone are available in patients with AUD only. This proposed research study is a double-blind controlled clinical trial of 200 Veterans with AUD randomized to either pioglitazone or placebo. The primary hypothesis is that Veterans with AUD who are currently drinking alcohol will have a greater reduction in heavy drinking days per week compared to those who receive placebo.
Methods: Male and Female Veterans who are above 18 years old, who are not seeking intensive outpatient alcohol treatment will be recruited from the Minneapolis and Long Beach VA Health Care Service's for the study. After screening visits and informed consent, participants who meet all inclusion and exclusion criteria and who sign the informed consent will be given a breathalyzer test and the following measures: The Structured Clinical Interview for DSM-5 (SCID), Obsessive Compulsive Drinking Scale (OCDS), Timeline Followback (TLFB), Beck Depression Inventory-2nd edition (BDI-II) and the PTSD Checklist (PCL-5). Participants will also provide a urine sample for a urine drug screen, Ethyl Glucuronide (EtG), and Ethyl Sulfate (EtS), and blood samples for ALT, AST and BNP (B-type natriuretic peptide). Women of childbearing potential will provide a urine sample for Beta-Human chorionic gonadotropin ( -HCG). Participants will then be randomized to receive either pioglitazone or placebo. The participants will be seen weekly for the first 4 weeks (visits 1,2,3,4- baseline or randomization visit will be visit 0) then every 2 weeks until the end of the study (week 6 or visit 5, week 8 or visit 6, week 10 or visit 7, week 12 or visit 8, and week 14 or visit 9) for a maximum of 12 visits (including the screening visit, baseline visit, and closeout visit). At week 16, there will be a termination or closeout visit after study medications have been tapered. During the first 2 weeks of the study, each subject will have their dose of pioglitazone (or placebo) increased to a dose of 45mg per day. In addition to the medication (pioglitazone or placebo all participants will receive Brief Behavioral Compliance Enhancement Treatment (BBCET) as their psychosocial treatment. This is a standardized 15-minute intervention that emphasizes medication adherence as a crucial element to change alcohol use behavior.
Alcohol use will be measured by the Timeline Follow-back method and biomarkers of alcohol use will also be measured to determine whether a reduction in alcohol correlates with reduced markers of alcohol use. In addition, the impact of pioglitazone on rumination and safety will be assessed with a variety of measures.
Relevance to Veterans Health: Veterans have high rates of AUD with significant impact on health, quality of life and mortality. In addition, the direct and indirect cost of AUD are high. Current medication treatment approaches are infrequently used and of only small to modest benefit. Pioglitazone has shown promise in several pre-clinical studies but no AUD clinically focused studies are available. If pioglitazone is found to be useful in reducing or eliminating alcohol use in Veterans it could be easily and rapidly repurposed to treat AUD, as it is already an FDA approved medication. Pioglitazone, given its unique mechanism of action, may offer an innovative approach to treating Veterans with AUD and thus help reduce the impact of this costly and difficult problem.
- Conditions
- Alcohol Use Disorder
- Being tested
- Brief Behavioral Compliance Enhancement Treatment
- Keywords
- Alcohol Use Disorder, Alcohol dependence, Craving
- Medical subject headings
- Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Brief Behavioral Compliance Enhancement TreatmentBehavioural
Also called BBCET
This is a standardized 15-minute intervention that emphasizes medication adherence as a crucial element to change alcohol use behavior.
| Study group | Role | What they receive |
|---|---|---|
| Pioglitazone | Experimental | Pioglitazone titrated to 45mg by mouth each day Receives: Behavioral: Brief Behavioral Compliance Enhancement Treatment |
| Placebo | Placebo comparator | placebo, identical 45mg pill Receives: Behavioral: Brief Behavioral Compliance Enhancement Treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Heavy Drinking Days Per Week Change
The primary outcome is change in heavy drinking days per week as measured by the Timeline Follow-back. A heavy drinking day is defined as : >4 standard drinks in a day for men and >3 standard drinks in a day for women
Measured: Change between baseline and 14 weeks
Secondary outcomes (4)
Number of Subjects With no Heavy Drinking for the Last 8 Weeks of the Study
The rate of no heavy drinking over the last 8 weeks of the study (weeks 6-14) is a responder analysis measure. This is the total count of participants of each group experiencing no heavy drinking days during weeks 7-14
Measured: heavy drinking between week 7 and 14
Number of Drinks Per Week
Mean number of standard drinks per week as measured by the Timeline Follow-back
Measured: Change in mean drinks per week from baseline to week 14
Alcohol Craving
Craving will be measured by the Obsessive Compulsive Drinking Scale (OCDS). Range is 0-56, greater scores indicates greater craving.
Measured: Change in mean obsessive compulsive drinking scale score from baseline to week 14
Ethyl Glucuronide (EtG) and Ethyl Sulfate (EtS) Positivity
EtG and EtS are direct metabolites of alcohol and remains in urine for up to 5 days after cessation from alcohol and they are highly sensitive with good specificity for alcohol use. ETG and ETS results are dichotomous and scored as either positive or negative for alcohol.
Measured: Change between baseline and 14 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2019
- Study start17 Jul 2019
- Primary completion29 Mar 2024
- Study completion29 Mar 2024
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.
- Other trials for Alcohol Use DisorderStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a randomized controlled parallel group study design
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 201 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Eric W. Dieperink, MD, Principal investigator, Minneapolis VA Health Care System, Minneapolis, MN
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03864146
- Sponsor's protocol ID
- NURA-015-18S
- Other IDs
- CX-001837-01
- Acronym
- PAUSE
- Status last verified
- Jun 2025
- First submitted
- 27 Feb 2019
- Last updated
- 13 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Trial of Pioglitazone for the Treatment of Alcohol Use Disorder
- ClinicalTrials.gov ID
- NCT03864146
- Acronym / sponsor ID
- PAUSE / NURA-015-18S
- Conditions
- Alcohol Use Disorder
- Keywords
- Alcohol Use Disorder, Alcohol dependence, Craving
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 201 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 17 Jul 2019 (actual)
- Primary completion
- 29 Mar 2024 (actual)
- Study completion
- 29 Mar 2024 (actual)
- First posted
- 6 Mar 2019 (actual)
- Results
- Posted 13 Jun 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Alcohol Use Disorder (AUD) is common among Veterans but medication treatment is used infrequently and the impact of these treatments are small to moderate at best. Pioglitazone, a medication FDA approved for diabetes, has been shown in pre-clinical studies to reduce alcohol. The proposed study will test the efficacy of pioglitazone to reduce alcohol use in a double-blind placebo controlled trial. Investigators plan to compare pioglitazone to placebo in 200 Veterans who have an AUD and who are currently drinking alcohol at two Veterans Affairs Health Care Centers. The primary hypothesis is that Veterans with an AUD who are currently drinking alcohol will have a greater reduction in alcohol use following treatment with pioglitazone compared to those treated with placebo.
Detailed description
Background: Alcohol use disorder (AUD) and heavy drinking are common among Veterans with 42.2% of Veterans having a life-time history of AUD and 14.8% screening positive for past-year probable AUD. Although treatments for AUD have improved over the past several decades, more effective interventions are needed. Pioglitazone is an FDA approved medication used to treat diabetes. Pioglitazone is a PPAR agonist and has been reported to decrease voluntary alcohol consumption of a 10% alcohol solution in rats genetically selected for high alcohol consumption. In addition, when rats had to perform an operant task to receive alcohol, pioglitazone reduced alcohol self-administration but not saccharin intake. These data suggest that pioglitazone reduces the motivation to consume alcohol. No clinical studies of pioglitazone are available in patients with AUD only. This proposed research study is a double-blind controlled clinical trial of 200 Veterans with AUD randomized to either pioglitazone or placebo. The primary hypothesis is that Veterans with AUD who are currently drinking alcohol will have a greater reduction in heavy drinking days per week compared to those who receive placebo.
Methods: Male and Female Veterans who are above 18 years old, who are not seeking intensive outpatient alcohol treatment will be recruited from the Minneapolis and Long Beach VA Health Care Service's for the study. After screening visits and informed consent, participants who meet all inclusion and exclusion criteria and who sign the informed consent will be given a breathalyzer test and the following measures: The Structured Clinical Interview for DSM-5 (SCID), Obsessive Compulsive Drinking Scale (OCDS), Timeline Followback (TLFB), Beck Depression Inventory-2nd edition (BDI-II) and the PTSD Checklist (PCL-5). Participants will also provide a urine sample for a urine drug screen, Ethyl Glucuronide (EtG), and Ethyl Sulfate (EtS), and blood samples for ALT, AST and BNP (B-type natriuretic peptide). Women of childbearing potential will provide a urine sample for Beta-Human chorionic gonadotropin ( -HCG). Participants will then be randomized to receive either pioglitazone or placebo. The participants will be seen weekly for the first 4 weeks (visits 1,2,3,4- baseline or randomization visit will be visit 0) then every 2 weeks until the end of the study (week 6 or visit 5, week 8 or visit 6, week 10 or visit 7, week 12 or visit 8, and week 14 or visit 9) for a maximum of 12 visits (including the screening visit, baseline visit, and closeout visit). At week 16, there will be a termination or closeout visit after study medications have been tapered. During the first 2 weeks of the study, each subject will have their dose of pioglitazone (or placebo) increased to a dose of 45mg per day. In addition to the medication (pioglitazone or placebo all participants will receive Brief Behavioral Compliance Enhancement Treatment (BBCET) as their psychosocial treatment. This is a standardized 15-minute intervention that emphasizes medication adherence as a crucial element to change alcohol use behavior.
Alcohol use will be measured by the Timeline Follow-back method and biomarkers of alcohol use will also be measured to determine whether a reduction in alcohol correlates with reduced markers of alcohol use. In addition, the impact of pioglitazone on rumination and safety will be assessed with a variety of measures.
Relevance to Veterans Health: Veterans have high rates of AUD with significant impact on health, quality of life and mortality. In addition, the direct and indirect cost of AUD are high. Current medication treatment approaches are infrequently used and of only small to modest benefit. Pioglitazone has shown promise in several pre-clinical studies but no AUD clinically focused studies are available. If pioglitazone is found to be useful in reducing or eliminating alcohol use in Veterans it could be easily and rapidly repurposed to treat AUD, as it is already an FDA approved medication. Pioglitazone, given its unique mechanism of action, may offer an innovative approach to treating Veterans with AUD and thus help reduce the impact of this costly and difficult problem.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This is a randomized controlled parallel group study design
| Arm | Type | Receives |
|---|---|---|
| Pioglitazone | Experimental | Behavioral: Brief Behavioral Compliance Enhancement TreatmentPioglitazone titrated to 45mg by mouth each day |
| Placebo | Placebo comparator | Behavioral: Brief Behavioral Compliance Enhancement Treatmentplacebo, identical 45mg pill |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- DSM-5 diagnosis of at least moderate alcohol use disorder using the SCID
- A mean of six heavy drinking days per month for the 3-months prior to baseline.
- Drinking at least 14 drinks for men or 7 drinks for women, or more per week for the 4 weeks preceding the screening visit.
- Willingness to provide contact information to confirm study follow-up appointments
- Ability to perform informed consent
Key exclusion criteria (10 listed)
- Current DSM-5 diagnosis of moderate to severe psychoactive substance use disorder (i.e. cocaine, opiates, methamphetamine) other than cannabis or nicotine
- Medical conditions contraindicating pioglitazone pharmacotherapy (e.g., congestive heart failure, clinically significant edema, clinically significant liver disease, hypoglycemia, diabetes, history of bladder cancer)
- Taking medications known to have significant drug interactions with the study medication (CYP2C8 inhibitors or inducers, antihyperglycemic medications)
- Cognitive or physical impairment that precludes study participation
- Currently and seriously suicidal (i.e., plan and intent)
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 |
|---|---|---|
| Brief Behavioral Compliance Enhancement TreatmentAlso: BBCETThis is a standardized 15-minute intervention that emphasizes medication adherence as a crucial element to change alcohol use behavior. | Behavioural | Pioglitazone, Placebo |
Primary outcome
Heavy Drinking Days Per Week Change
Time frame: Change between baseline and 14 weeks
The primary outcome is change in heavy drinking days per week as measured by the Timeline Follow-back. A heavy drinking day is defined as : >4 standard drinks in a day for men and >3 standard drinks in a day for women
4 secondary outcomes
Number of Subjects With no Heavy Drinking for the Last 8 Weeks of the Study
Time frame: heavy drinking between week 7 and 14
Number of Drinks Per Week
Time frame: Change in mean drinks per week from baseline to week 14
Alcohol Craving
Time frame: Change in mean obsessive compulsive drinking scale score from baseline to week 14
Ethyl Glucuronide (EtG) and Ethyl Sulfate (EtS) Positivity
Time frame: Change between baseline and 14 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Eric W. Dieperink, MD principal investigator
Minneapolis VA Health Care System, Minneapolis, MN
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Brief Behavioral Compliance Enhancement Treatment in people with Alcohol Use Disorder, run by VA Office of Research and Development at 2 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 10 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 13 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jun 2025). 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?
Heavy Drinking Days Per Week Change (time frame: Change between baseline and 14 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Jun 2025.