Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 9 of 57 for:    Behaviors and Mental Disorders[CONDITION-BROWSE-BRANCH] | Recruiting, Not yet recruiting, Available Studies | ( Map: Minnesota, United States ) | NIH, U.S. Fed

Pioglitazone for the Treatment of Alcohol Use Disorder (PAUSE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03864146
Recruitment Status : Not yet recruiting
First Posted : March 6, 2019
Last Update Posted : June 21, 2019
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Alcohol Use Disorder Behavioral: Brief Behavioral Compliance Enhancement Treatment Not Applicable

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is a randomized controlled parallel group study design
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Trial of Pioglitazone for the Treatment of Alcohol Use Disorder
Estimated Study Start Date : June 28, 2019
Estimated Primary Completion Date : January 6, 2023
Estimated Study Completion Date : May 5, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Alcohol

Arm Intervention/treatment
Experimental: Pioglitazone
Pioglitazone titrated to 45mg by mouth each day
Behavioral: Brief Behavioral Compliance Enhancement Treatment
This is a standardized 15-minute intervention that emphasizes medication adherence as a crucial element to change alcohol use behavior.
Other Name: BBCET

Placebo Comparator: Placebo
placebo, identical 45mg pill
Behavioral: Brief Behavioral Compliance Enhancement Treatment
This is a standardized 15-minute intervention that emphasizes medication adherence as a crucial element to change alcohol use behavior.
Other Name: BBCET




Primary Outcome Measures :
  1. heavy drinking days per week change [ Time Frame: baseline and weekly for 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


Secondary Outcome Measures :
  1. No heavy drinking for the last 8 weeks of the study [ Time Frame: heavy drinking between week 6 and 14. ]
    The rate of no heavy drinking over the last 8 weeks of the study (weeks 6-14) is a responder analysis measures.

  2. Number of drinks per week [ Time Frame: baseline and weekly for 14 weeks ]
    Number of standard drinks per week as measured by the Timeline Follow-back

  3. Alcohol craving [ Time Frame: baseline, weekly through week 8 then week 10, 12 and 14. ]
    Craving will be measured by the Obsessive Compulsive Drinking Scale (OCDS). Range is 0-56, greater scores indicates greater craving.

  4. ethyl glucuronide (EtG) and ethyl sulfate (EtS) concentration [ Time Frame: Baseline, week 4, 8 ,12 and 14 ]
    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.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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)
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03864146


Contacts
Layout table for location contacts
Contact: Eric W Dieperink, MD (612) 725-2000 ext 2037 eric.dieperink@va.gov

Locations
Layout table for location information
United States, California
VA Long Beach Healthcare System, Long Beach, CA Not yet recruiting
Long Beach, California, United States, 90822
Contact: Juan L Miranda, BS    526-826-8000    Juan.MirandaJr@va.gov   
Contact: Peter Hauser, MD    5268268000 ext 2629    peter.hauser2@va.gov   
United States, Minnesota
Minneapolis VA Health Care System, Minneapolis, MN Not yet recruiting
Minneapolis, Minnesota, United States, 55417
Contact: Eric W Dieperink, MD    612-725-2000 ext 2037    eric.dieperink@va.gov   
Principal Investigator: Eric W. Dieperink, MD         
Sponsors and Collaborators
VA Office of Research and Development
Investigators
Layout table for investigator information
Principal Investigator: Eric W. Dieperink, MD Minneapolis VA Health Care System, Minneapolis, MN

Layout table for additonal information
Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT03864146     History of Changes
Other Study ID Numbers: NURA-015-18S
CX-001837-01 ( Other Grant/Funding Number: Veterans Health CSR&D )
First Posted: March 6, 2019    Key Record Dates
Last Update Posted: June 21, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by VA Office of Research and Development:
Alcohol Use Disorder
Alcohol dependence
Craving

Additional relevant MeSH terms:
Layout table for MeSH terms
Disease
Alcohol Drinking
Alcoholism
Pathologic Processes
Drinking Behavior
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Ethanol
Pioglitazone
Anti-Infective Agents, Local
Anti-Infective Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Hypoglycemic Agents