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

NCT03060772 | Terminated Phase 2 DMC FDA Drug

• 2 other identifiers: IRB000719081R01AA025857
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Alcoholism

Keywords

Pulmonary Medicine; Oxidative Stress; Pioglitazone; Immunology; Addictive/Compulsive Behavior

Outcome Measures

Primary Outcomes (1)

• Change in phagocytic index

  The change in phagocytic index will be determined between the alcohol use disorder study arms to examine the effect of PIO treatment. Phagocytic index of the alveolar macrophage is the rate at which particles are cleared from a culture. The phagocytic index is a well-established marker of immune function and its improvement with pioglitazone (PIO) treatment would indicate reversal of the alcoholic lung phenotype. The phagocytic index will be measured in bronchoalveolar lavage (BAL) fluids.

  Baseline, After 2-4 weeks

Secondary Outcomes (8)

• Change in nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase)

  Baseline, After 2-4 weeks

• Change in alveolar macrophage oxidative stress

  Baseline, After 2-4 weeks

• Change in redox couple glutathione/glutathione disulfide (GSH/GSSG)

  Baseline, After 2-4 weeks

• Change in cysteine/cystine (Cys/CySS) redox potential

  Baseline, After 2-4 weeks

• Comparison of nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase)

  Baseline (control group), After 2-4 weeks (treatment group)

Study Arms (3)

Alcohol use disorder - Pioglitazone Treatment

EXPERIMENTAL

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.

Drug: Pioglitazone

Alcohol use disorder - No Pioglitazone

NO INTERVENTION

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.

Healthy controls without alcohol use disorder

NO INTERVENTION

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.

Interventions

Pioglitazone 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.

Also known as: Actos

Alcohol use disorder - Pioglitazone Treatment

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

Atlanta VA Medical Center

Decatur, Georgia, 30033, United States

Location

MeSH Terms

Conditions

Alcoholism; Compulsive Behavior

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Impulsive Behavior; Behavior

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• David Guidot, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: Individuals with alcohol use disorder will be randomized to receive the study medication, pioglitazone, or no medication (12 in each group). A third group of healthy individuals who do not have an alcohol use disorder will also be enrolled to serve as an additional comparison group.

Study Record Dates

• First Submitted: February 19, 2017
• First Posted: February 23, 2017
• Study Start: January 3, 2018
• Primary Completion: January 28, 2020
• Study Completion: January 28, 2020
• Last Updated: February 14, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)