Effects of Pioglitazone on Stress Reactivity and Alcohol Craving

The purpose of this study is to examine the effects of pioglitazone on stress-induced relapse risk in a laboratory model and to examine the effects of pioglitazone on drinking, stress/anxiety, and alcohol craving in the natural environment

Study Overview

• Status: Completed
• Conditions: Alcohol Use Disorder
• Intervention / Treatment: Drug: Pioglitazone; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center of Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• treatment-seeking individuals diagnosed with Alcohol Use Disorder Diagnostic (AUD) and Statistical Manual of Mental Disorders, 5th Edition (DSM-5)
• fluent in English
• past month excessive alcohol use (>7 drinks/week for woman, >14 drinks/week for men, >3 drinks/occasion for women>4 drinks/occasion for men)
• exhibit baseline measures of either 1) 8-23 on HAM-A indicative of mild to moderate anxiety, 2) 14-26 on PSS Score indicative of moderate stress, or 3) ≥2 on Drinking Motives Questionnaire (DMQ-R) questions related to drinking indicating that individuals drink at least "some of the time" to cope
• exhibit increased stress reactivity (increased physiological response and/or self-report) at the baseline stress reactivity assessment
• females will need to agree to use of barrier methods of contraception due to pioglitazone's effects on plasma concentrations of oral contraceptives

Exclusion Criteria:

• Exhibit severe scores on the HAM-A, PSS, or PTSD checklist (PCL-5) - may be enrolled at the discretion of the admitting physician (Dr. Weaver)
• physical dependence on alcohol (CIWAA > 10)
• greater than mild substance use disorder on drugs other than alcohol, nicotine, and marijuana
• contraindications for taking pioglitazone
• medical conditions (e.g., congestive heart failure, clinically significant edema, clinically significant liver disease, hypoglycemia, diabetes, history of bladder cancer)
• contraindicating pioglitazone pharmacotherapy or taking contraindicated medications (e.g., CYP2C8 inhibitors or inducers, antihyperglycemic medications)
• be pregnant, nursing, or planning on becoming pregnant during the course of the study
• have any other illness, condition, or use of medications, which in the opinion of the PI and/or admitting physician would preclude safe and/or successful completion of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Pill capsules will look same as that of active drug.
Experimental: Pioglitazone	Drug: Pioglitazone; For the current trial we will follow recommended adult initial dosing at 30 mg/d to reach maintenance dose of 45 mg/d by end of week 1, which is within standard titration parameters as per the investigator's brochure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Stress-reactivity as Assessed by Heart Rate Change During the Cold Pressor Task (CPT)	During the cold pressor task (CPT), participants will submerge their dominant arm in an ice-water bath for up to 2 minutes. Heart rate will be collected before and after CPT. The change in Heart rate will be reported as [(Heart rate post cold pressor task) - (Heart rate pre cold pressor task)].	Baseline, about 2 minutes after the start of the cold pressor task
Change in Stress-reactivity as Assessed by Heart Rate Change During the Cold Pressor Task (CPT)	During the cold pressor task (CPT), participants will submerge their dominant arm in an ice-water bath for up to 2 minutes. Heart rate will be collected before and after CPT. The change in Heart rate will be reported as [(Heart rate post cold pressor task) - (Heart rate pre cold pressor task)].	Week 8, about 2 minutes after the start of the Cold Pressor Task
Change in Stress-reactivity as Assessed by Change in Systolic Blood Pressure During the Cold Pressor Task (CPT)	During the cold pressor task (CPT), participants will submerge their dominant arm in an ice-water bath for up to 2 minutes. Systolic Blood Pressure will be collected before and after CPT. The change in Systolic Blood Pressure will be reported as [( Systolic Blood Pressure at post cold pressor task) - (Systolic Blood Pressure at pre cold pressor task)].	Baseline, about 2 minutes after the start of the Cold Pressor Task
Change in Stress-reactivity as Assessed by Change in Systolic Blood Pressure During the Cold Pressor Task (CPT)	During the cold pressor task (CPT), participants will submerge their dominant arm in an ice-water bath for up to 2 minutes. Systolic Blood Pressure will be collected before and after CPT. The change in Systolic Blood Pressure will be reported as [( Systolic Blood Pressure at post cold pressor task) - (Systolic Blood Pressure at pre cold pressor task)].	Week 8, about 2 minutes after the start of the Cold Pressor Task
Change in Stress-reactivity as Assessed by Diastolic Blood Pressure Change During the Cold Pressor Task (CPT)Cold Pressor Task (CPT)	During the cold pressor task (CPT), participants will submerge their dominant arm in an ice-water bath for up to 2 minutes. Diastolic Blood Pressure will be collected before and after CPT. The change in Diastolic Blood Pressure will be reported as [( Diastolic Blood Pressure post cold pressor task) - (Diastolic Blood Pressure pre cold pressor task)].	Baseline, about 2 minutes after the start of the Cold Pressor Task
Change in Stress-reactivity as Assessed by Diastolic Blood Pressure Change During the Cold Pressor Task (CPT)Cold Pressor Task (CPT)	During the cold pressor task (CPT), participants will submerge their dominant arm in an ice-water bath for up to 2 minutes. Diastolic Blood Pressure will be collected before and after CPT. The change in Diastolic Blood Pressure will be reported as [( Diastolic Blood Pressure post cold pressor task) - (Diastolic Blood Pressure pre cold pressor task)].	Week 8, about 2 minutes after the start of the Cold Pressor Task
Change in Stress-reactivity as Assessed by Salivary Cortisol Level Change During the Cold Pressor Task (CPT)	During the cold pressor task (CPT), participants will submerge their dominant arm in an ice-water bath for up to 2 minutes. Saliva samples will be collected before and after the CPT, and cortisol levels in the saliva samples will be assessed. The change in cortisol level will be reported as [(cortisol level at post cold pressor task) - (cortisol level pre cold pressor task)].	baseline, about 32 minutes after the start of the Cold Pressor Task
Change in Stress-reactivity as Assessed by Salivary Cortisol Level Change During the Cold Pressor Task (CPT)	During the cold pressor task (CPT), participants will submerge their dominant arm in an ice-water bath for up to 2 minutes. Saliva samples will be collected before and after the CPT, and cortisol levels in the saliva samples will be assessed. The change in cortisol level will be reported as [(cortisol level at post cold pressor task) - (cortisol level pre cold pressor task)].	week 8, about 32 minutes after the start of the Cold Pressor Task
Change in Alcohol Craving as Assessed by Alcohol Craving Scale Score During the Cold Pressor Task (CPT)	The alcohol craving scale has a total score from 0 to 50, higher score indicating greater alcohol craving. During the cold pressor task (CPT), participants will submerge their dominant arm in an ice-water bath for up to 2 minutes. The Alcohol Craving Scale will be administered before and after CPT. The change in alcohol craving will be reported as [(Alcohol craving scale score post cold pressor task) - (Alcohol craving scale score pre cold pressor task)]. -- a negative value indicates a decrease in alcohol craving.	baseline, about 2 minutes after the start of the CPT
Change in Alcohol Craving as Assessed by Alcohol Craving Scale Score During the Cold Pressor Task (CPT)	The alcohol craving scale has a total score from 0 to 50, higher score indicating greater alcohol craving. During the cold pressor task (CPT), participants will submerge their dominant arm in an ice-water bath for up to 2 minutes. The Alcohol Craving Scale will be administered before and after CPT. The change in alcohol craving will be reported as [(Alcohol craving scale score post cold pressor task) - (Alcohol craving scale score pre cold pressor task)]. -- a negative value indicates a decrease in alcohol craving.	week 8, about 2 minutes after the start of the CPT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Drinking Habit as Assessed by the Number of Drinks Per Day (Timeline Followback Method)	The Timeline Followback (TLFB) method was used to assess alcohol consumption by asking study participants to self-report their number of drinks consumed each day over the past week. The change in drinking habit is reported as [(number of drinks per day at week 8) - (number of drinks per day at baseline)].-- a negative value indicates a decrease in alcohol consumption over time.	baseline, week 8
Change in Drinking Habit as Assessed by the Number of Heavy Drinking Days (Timeline Followback Method)	The Timeline Followback (TLFB) method was used to assess alcohol consumption by asking study participants to self-report their number of drinks consumed each day over the past week. Heavy drinking is defined as 4 drinks or more per day for females and 5 or more drinks per day for males. The change in drinking habit is reported as [(number of heavy drinking days at week 8) - (number of heavy drinking days at baseline)].--A negative value indicates a decrease in the number of heavy drinking days over time.	baseline, week 8
Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)	The Hamilton Anxiety Rating Scale(HAM-A) is a 14 item questionnaire scored from 0 (not present) to 4 (very severe). The 14 items are summed to obtain a total score ranging from 0 to 56, high scores indicating greater anxiety.	Baseline
Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)	The Hamilton Anxiety Rating Scale(HAM-A) is a 14 item questionnaire scored from 0 (not present) to 4 (very severe). The 14 items are summed to obtain a total score ranging from 0 to 56, high scores indicating greater anxiety.	week 1
Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)	The Hamilton Anxiety Rating Scale(HAM-A) is a 14 item questionnaire scored from 0 (not present) to 4 (very severe). The 14 items are summed to obtain a total score ranging from 0 to 56, high scores indicating greater anxiety.	week 2
Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)	The Hamilton Anxiety Rating Scale(HAM-A) is a 14 item questionnaire scored from 0 (not present) to 4 (very severe). The 14 items are summed to obtain a total score ranging from 0 to 56, high scores indicating greater anxiety.	week 3
Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)	The Hamilton Anxiety Rating Scale(HAM-A) is a 14 item questionnaire scored from 0 (not present) to 4 (very severe). The 14 items are summed to obtain a total score ranging from 0 to 56, high scores indicating greater anxiety.	week 4
Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)	The Hamilton Anxiety Rating Scale(HAM-A) is a 14 item questionnaire scored from 0 (not present) to 4 (very severe). The 14 items are summed to obtain a total score ranging from 0 to 56, high scores indicating greater anxiety.	week 5
Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)	The Hamilton Anxiety Rating Scale(HAM-A) is a 14 item questionnaire scored from 0 (not present) to 4 (very severe). The 14 items are summed to obtain a total score ranging from 0 to 56, high scores indicating greater anxiety.	week 6
Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)	The Hamilton Anxiety Rating Scale(HAM-A) is a 14 item questionnaire scored from 0 (not present) to 4 (very severe). The 14 items are summed to obtain a total score ranging from 0 to 56, high scores indicating greater anxiety.	week 7
Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)	The Hamilton Anxiety Rating Scale(HAM-A) is a 14 item questionnaire scored from 0 (not present) to 4 (very severe). The 14 items are summed to obtain a total score ranging from 0 to 56, high scores indicating greater anxiety.	week 8
Alcohol Craving as Assessed by the Pennsylvania Alcohol Craving Scale(PACS)	The Pennsylvania Alcohol Craving Scale(PACS) total score ranges from 0 to 30, higher scores indicating more alcohol cravings.	baseline
Alcohol Craving as Assessed by the Pennsylvania Alcohol Craving Scale(PACS)	The Pennsylvania Alcohol Craving Scale(PACS) total score ranges from 0 to 30, higher scores indicating more alcohol cravings.	Week 8
Stress as Assessed by the Perceived Stress Scale(PSS)	The Perceived Stress Scale(PSS) is a 10 item questionnaire scored from 0 (never) to 4 (very often). The 10 items are summed to obtain a total score ranging from 0 to 40, high scores indicating greater stress.	Baseline
Stress as Assessed by the Perceived Stress Scale(PSS)	The Perceived Stress Scale(PSS) is a 10 item questionnaire scored from 0 (never) to 4 (very often). The 10 items are summed to obtain a total score ranging from 0 to 40, high scores indicating greater stress.	Week 1
Stress as Assessed by the Perceived Stress Scale(PSS)	The Perceived Stress Scale(PSS) is a 10 item questionnaire scored from 0 (never) to 4 (very often). The 10 items are summed to obtain a total score ranging from 0 to 40, high scores indicating greater stress.	Week 2
Stress as Assessed by the Perceived Stress Scale(PSS)	The Perceived Stress Scale(PSS) is a 10 item questionnaire scored from 0 (never) to 4 (very often). The 10 items are summed to obtain a total score ranging from 0 to 40, high scores indicating greater stress.	Week 3
Stress as Assessed by the Perceived Stress Scale(PSS)	The Perceived Stress Scale(PSS) is a 10 item questionnaire scored from 0 (never) to 4 (very often). The 10 items are summed to obtain a total score ranging from 0 to 40, high scores indicating greater stress.	Week 4
Stress as Assessed by the Perceived Stress Scale(PSS)	The Perceived Stress Scale(PSS) is a 10 item questionnaire scored from 0 (never) to 4 (very often). The 10 items are summed to obtain a total score ranging from 0 to 40, high scores indicating greater stress.	Week 5
Stress as Assessed by the Perceived Stress Scale(PSS)	The Perceived Stress Scale(PSS) is a 10 item questionnaire scored from 0 (never) to 4 (very often). The 10 items are summed to obtain a total score ranging from 0 to 40, high scores indicating greater stress.	Week 6
Stress as Assessed by the Perceived Stress Scale(PSS)	The Perceived Stress Scale(PSS) is a 10 item questionnaire scored from 0 (never) to 4 (very often). The 10 items are summed to obtain a total score ranging from 0 to 40, high scores indicating greater stress.	Week 7
Stress as Assessed by the Perceived Stress Scale(PSS)	The Perceived Stress Scale(PSS) is a 10 item questionnaire scored from 0 (never) to 4 (very often). The 10 items are summed to obtain a total score ranging from 0 to 40, high scores indicating greater stress.	Week 8

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Principal Investigator: Jin H Yoon, PhD, The University of Texas Health Science Center, Houston

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2022
• Primary Completion (Actual): August 16, 2024
• Study Completion (Actual): August 16, 2024

Study Registration Dates

• First Submitted: October 25, 2021
• First Submitted That Met QC Criteria: October 25, 2021
• First Posted (Actual): November 4, 2021

Study Record Updates

• Last Update Posted (Estimated): August 27, 2025
• Last Update Submitted That Met QC Criteria: August 8, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Anxiety; Stress; alcohol; Pioglitazone
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Anxiety Disorders; Alcoholism; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Substandard Drugs; Pharmaceutical Preparations; Thiazoles; Azoles; Thiazolidinediones; Pioglitazone; Counterfeit Drugs
• Other Study ID Numbers: HSC-MS-18-0922 (main study); 1R21AA027273-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No