Phase 2 N=55 Randomized Quadruple-blind Treatment

Effects of Pioglitazone on Stress Reactivity and Alcohol Craving

Alcohol Use Disorder

Bottom Line

View on ClinicalTrials.gov: NCT05107765 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Aug 2025

Primary outcome: Primary: Change in Stress-reactivity as Assessed by Heart Rate Change During the Cold Pressor Task (CPT) — 5.138; 12.154 beats per minutes (bpm)

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Pioglitazone (Drug); Placebo (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: The University of Texas Health Science Center, Houston
Primary completion: Aug 2024

Outcome Measures

Outcome	Result	p-value
PRIMARY Change in Stress-reactivity as Assessed by Heart Rate Change During the Cold Pressor Task (CPT)	4.444; 11.182	—
PRIMARY Change in Stress-reactivity as Assessed by Heart Rate Change During the Cold Pressor Task (CPT)	4.444; 11.182	—
PRIMARY Change in Stress-reactivity as Assessed by Change in Systolic Blood Pressure During the Cold Pressor Task (CPT)	17.778; 21.091	—
PRIMARY Change in Stress-reactivity as Assessed by Change in Systolic Blood Pressure During the Cold Pressor Task (CPT)	17.778; 21.091	—
PRIMARY Change in Stress-reactivity as Assessed by Diastolic Blood Pressure Change During the Cold Pressor Task (CPT)Cold Pressor Task (CPT)	12; 13.545	—
PRIMARY Change in Stress-reactivity as Assessed by Diastolic Blood Pressure Change During the Cold Pressor Task (CPT)Cold Pressor Task (CPT)	12; 13.545	—
PRIMARY Change in Stress-reactivity as Assessed by Salivary Cortisol Level Change During the Cold Pressor Task (CPT)	427.61; 447.417	—
PRIMARY Change in Stress-reactivity as Assessed by Salivary Cortisol Level Change During the Cold Pressor Task (CPT)	427.61; 447.417	—
PRIMARY Change in Alcohol Craving as Assessed by Alcohol Craving Scale Score During the Cold Pressor Task (CPT)	0.367; 1.173	—
PRIMARY Change in Alcohol Craving as Assessed by Alcohol Craving Scale Score During the Cold Pressor Task (CPT)	0.367; 1.173	—
SECONDARY Change in Drinking Habit as Assessed by the Number of Drinks Per Day (Timeline Followback Method)	-1.229; -0.714	—
SECONDARY Change in Drinking Habit as Assessed by the Number of Heavy Drinking Days (Timeline Followback Method)	-5.5; -3.591	—
SECONDARY Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)	4.167; 2.952	—
SECONDARY Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)	4.167; 2.952	—
SECONDARY Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)	4.167; 2.952	—
SECONDARY Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)	4.167; 2.952	—
SECONDARY Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)	4.167; 2.952	—
SECONDARY Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)	4.167; 2.952	—
SECONDARY Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)	4.167; 2.952	—
SECONDARY Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)	4.167; 2.952	—
SECONDARY Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)	4.167; 2.952	—
SECONDARY Alcohol Craving as Assessed by the Pennsylvania Alcohol Craving Scale(PACS)	5.6111; 7.409	—
SECONDARY Alcohol Craving as Assessed by the Pennsylvania Alcohol Craving Scale(PACS)	5.6111; 7.409	—
SECONDARY Stress as Assessed by the Perceived Stress Scale(PSS)	11.222; 12.318	—
SECONDARY Stress as Assessed by the Perceived Stress Scale(PSS)	11.222; 12.318	—
SECONDARY Stress as Assessed by the Perceived Stress Scale(PSS)	11.222; 12.318	—
SECONDARY Stress as Assessed by the Perceived Stress Scale(PSS)	11.222; 12.318	—
SECONDARY Stress as Assessed by the Perceived Stress Scale(PSS)	11.222; 12.318	—
SECONDARY Stress as Assessed by the Perceived Stress Scale(PSS)	11.222; 12.318	—
SECONDARY Stress as Assessed by the Perceived Stress Scale(PSS)	11.222; 12.318	—
SECONDARY Stress as Assessed by the Perceived Stress Scale(PSS)	11.222; 12.318	—
SECONDARY Stress as Assessed by the Perceived Stress Scale(PSS)	11.222; 12.318	—

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

Eligibility Criteria

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT05107765). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.