Effects of Pioglitazone on Stress Reactivity and Alcohol Craving

NCT05107765 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: HSC-MS-18-0922 (main study)1R21AA027273-01A1
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Alcohol Use Disorder

Keywords

alcohol; Pioglitazone; Stress; Anxiety

Outcome Measures

Primary Outcomes (10)

• 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 Outcomes (22)

• Change in Drinking Habit as Assessed by the Number of Drinks Per Day (Timeline Followback Method)

  baseline, week 8

• Change in Drinking Habit as Assessed by the Number of Heavy Drinking Days (Timeline Followback Method)

  baseline, week 8

• Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)

  Baseline

• Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)

  week 1

• Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)

  week 2

Study Arms (2)

Pioglitazone

EXPERIMENTAL

Drug: Pioglitazone

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Pioglitazone DRUG

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.

Pioglitazone

Placebo DRUG

Pill capsules will look same as that of active drug.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

The University of Texas Health Science Center of Houston

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Alcoholism; Anxiety Disorders

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

Due to technical problems, the data for the outcome measure "Change in Stress-reactivity as Assessed by Salivary Cortisol Level Change During the Cold Pressor Task (CPT)" at both baseline and Week 8 were found to be unreliable.

Results Point of Contact

• Title: Jin H Yoon, PhD
• Organization: The University of Texas Health Science Center of Houston

jin.ho.yoon@uth.tmc.edu

713-486-2800

Study Officials

• Jin H Yoon, PhD

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 25, 2021
• First Posted: November 4, 2021
• Study Start: May 12, 2022
• Primary Completion: August 16, 2024
• Study Completion: August 16, 2024
• Last Updated: August 27, 2025
• Results First Posted: August 27, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)