A Study of Pleiotropic Pioglitazone Effects on the Alcoholic Lung (APPEAL Study)

NCT ID: NCT03060772

Last Updated: 2023-02-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-03
• Study Completion Date: 2020-01-28

Brief Summary

This study is a single center, open-label, randomized clinical trial to determine the effect of pioglitazone (PIO) treatment on alveolar macrophage immune function, redox stress, and NADPH oxidase expression in outpatient alcoholic subjects. The researchers will recruit a cohort of otherwise healthy patients with an alcoholic use disorder from the Substance Abuse Treatment Program at the Atlanta Veterans Affairs (VA) Medical Center and randomize them to receive the usual treatment for two to four weeks or to the usual treatment plus PIO treatment for two to four weeks. There will also be a healthy control group (matched on age, gender, and smoking status) that will receive no treatment. To measure the effect of pioglitazone, participants will undergo a bronchoscopy before taking the study drug and then again 2-4 weeks later to look for changes. The bronchoscopy will allow researchers to obtain fluid from the lungs to see how well their immune cells respond to bacteria by determining phagocytic capacity.

Detailed Description

Alcohol abuse is a major burden on society and an enormous problem in the veteran population. Many people are aware that chronic alcohol ingestion can cause serious health problems like liver injury and brain damage but chronic alcohol consumption can also hurt the lungs. People who regularly drink more than the daily maximum levels recommended by the Centers for Disease Control and Prevention (CDC) (1 drink per day for women or 2 drinks per day for men) are more likely to suffer from pneumonia and acute lung injuries.

The primary goal of this clinical research study is to determine if a Food and Drug Administration (FDA) approved diabetes drug, called pioglitazone, can improve the lung immune defenses in otherwise healthy alcoholics. There is strong evidence from experimental animal models that pioglitazone preserves lung health even during daily alcohol ingestion.

This National Institutes of Health (NIH) funded project will recruit veterans who are patients at the Atlanta VA Hospital. Half of the participants will be randomly assigned to receive pioglitazone and half will be assigned to receive no treatment. Participants assigned to pioglitazone will take the pill once per day for two to four weeks. To measure the effect of pioglitazone, participants will undergo a procedure called a bronchoscopy before taking the study drug and then again 2-4 weeks later to look for changes. The bronchoscopy will allow researchers to obtain fluid from the lungs to see how well their immune cells respond to bacteria (by determining phagocytic capacity). The researchers also plan to enroll 12 healthy veteran patients who do not drink. These participants will undergo a one-time bronchoscopy and no other visits will be required of them.

The findings from this study will guide future, larger scale clinical trials to determine if pioglitazone can be used in the clinical setting to improve outcomes in alcoholics who develop pneumonia or acute lung injury.

Conditions

Alcoholism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Alcohol use disorder - Pioglitazone Treatment

Participants with alcohol use disorder randomized to this group will receive pioglitazone. Study procedures include a bronchoscopy at baseline and an additional bronchoscopy after taking the study medication for 2 to 4 weeks.

Group Type: EXPERIMENTAL

Pioglitazone

Intervention Type: DRUG

Participants will take 30 mg of pioglitazone once daily for a total of two to four weeks for those randomized to therapy, until the next bronchoscopy is performed. Participants will receive 14 to 28 tablets of active pioglitazone, which is enough to complete the minimum 14-day course of therapy.

Alcohol use disorder - No Pioglitazone

Participants with alcohol use disorder randomized to this group will receive their usual care but will not receive pioglitazone. Study procedures include a bronchoscopy at baseline and an additional bronchoscopy 2 to 4 weeks later.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Healthy controls without alcohol use disorder

Healthy individuals who do not have alcohol use disorder will be enrolled will serve as a control group. Healthy controls will be a matched to participants receiving the treatment based on age, gender, and smoking status. This group will have a single bronchoscopy.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Pioglitazone

Participants will take 30 mg of pioglitazone once daily for a total of two to four weeks for those randomized to therapy, until the next bronchoscopy is performed. Participants will receive 14 to 28 tablets of active pioglitazone, which is enough to complete the minimum 14-day course of therapy.

Intervention Type: DRUG

Other Intervention Names

Actos

Eligibility Criteria

Inclusion Criteria

• Active alcohol use disorder, with last alcoholic drink within 8 days of randomization (for those in the alcohol use disorder arms)

Exclusion Criteria

• History of diabetes
• History of heart failure
• History of cirrhosis of the liver
• Elevation of liver enzymes greater than 2.5 times upper limit of normal
• History of bladder cancer
• Primary substance of abuse is something other than alcohol
• Current abnormal chest x-ray or other evidence of significant lung disease
• HIV-positive
• Renal impairment, defined as glomerular filtration rate (GFR) <60
• Current pregnancy or planning to become pregnant in the next 6 months
• Currently on pioglitazone treatment for another reason
• Contraindication to treatment with pioglitazone
• Any active and uncontrolled medical problem that may negatively impact the study results
• Currently on an oral steroid or inhaled corticosteroid
• History of profound psychiatric problems, poor compliance, or other psycho-social issues that may negatively impact participation
• Inability to give informed consent (i.e., limited cognitive capacity)
• Non-English speaking

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIH

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

David M. Guidot

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

David Guidot, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Atlanta VA Medical Center

Decatur, Georgia, United States

Countries

United States

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

1R01AA025857

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00071908

Identifier Type: -

Identifier Source: org_study_id