Effects of Pioglitazone on Stress Reactivity and Alcohol Craving (Pilot)

The purpose of this study is to assess the effect of pioglitazone on stress- and alcohol-related measures in treatment-seeking individuals with alcohol use disorder (AUD) and elevated levels of stress and anxiety.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• treatment-seeking individuals diagnosed with AUD diagnostic statistical manual 5 (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)14
• baseline Hamilton Anxiety Rating Scale (HAM-A) or Perceived Stress Scale (PSS) core indicative of mild to moderate anxiety (score 8 to 23) or moderate stress (score 14 to 26), respectively
• increase in alcohol craving following the baseline stress reactivity assessment.

Exclusion Criteria:

• Individuals will be excluded for exhibiting severe scores on the HAM-A, PSS, or post-traumatic (PTSD) checklist (PCL-5) at the discretion of the admitting physician
• physical dependence on alcohol Alcohol Use Disorders Inventory (AUDIT) score indicative of severe alcohol dependence (≥13 for women, ≥15 for men)
• greater than mild substance use disorder on drugs other than alcohol, nicotine, and marijuana
• contraindications for taking pioglitazone; medical conditions contraindicating pioglitazone pharmacotherapy or taking contraindicated 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: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

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 week 2, 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)	The cold pressor task (CPT) a stress-inducer in human laboratory studies that elicits moderate activation of the sympathetic nervous system and limited activation of the HPA-axis. During CPT, participants will submerge their dominant arm in an ice-water bath for up to 2 minutes, and heart rate will be measured before and after CPT. The heart rate change for each time point is calculated as heart rate after CPT minus the heart rate before CPT. This outcome measure reports the heart rate change at week 4 minus the heart rate change at baseline.	baseline, week 4
Change in Stress-reactivity as Assessed by Change in Systolic Blood Pressure During the Cold Pressor Task (CPT)	The cold pressor task (CPT) a stress-inducer in human laboratory studies that elicits moderate activation of the sympathetic nervous system and limited activation of the HPA-axis. During CPT, participants will submerge their dominant arm in an ice-water bath for up to 2 minutes, and blood pressure will be measured before and after CPT. The blood pressure change for each time point is calculated as blood pressure after CPT minus the blood pressure before CPT. This outcome measure reports the blood pressure change at week 4 minus the blood pressure change at baseline.	baseline, week 4
Change in Stress-reactivity as Assessed by Diastolic Blood Pressure Change During the Cold Pressor Task (CPT)	The cold pressor task (CPT) a stress-inducer in human laboratory studies that elicits moderate activation of the sympathetic nervous system and limited activation of the HPA-axis. During CPT, participants will submerge their dominant arm in an ice-water bath for up to 2 minutes, and blood pressure will be measured before and after CPT. The blood pressure change for each time point is calculated as blood pressure after CPT minus the blood pressure before CPT. This outcome measure reports the blood pressure change at week 4 minus the blood pressure change at baseline.	baseline, week 4
Change in Stress-reactivity as Assessed by Salivary Cortisol Level Change During the Cold Pressor Task (CPT)	The cold pressor task (CPT) a stress-inducer in human laboratory studies that elicits moderate activation of the sympathetic nervous system and limited activation of the HPA-axis. During CPT, participants will submerge their dominant arm in an ice-water bath for up to 2 minutes, and salivary cortisol level will be measured before and after CPT. The salivary cortisol level change for each time point is calculated as salivary cortisol level after CPT minus the salivary cortisol level before CPT. This outcome measure reports the salivary cortisol level change at week 4 minus the salivary cortisol level change at baseline.	baseline, week 4
Change in Stress-reactivity as Assessed by Self-report on a Visual Analogue Scale (VAS)	The visual analogue scale (VAS) ranges from 0-10, with a higher score indicating higher stress.	baseline, week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Alcohol Use as Indicated by Self Report Using the Alcohol Timeline Followback (TLFB)	The Alcohol Timeline Followback (TLFB) is a drinking assessment method that obtains an estimate of daily drinking. Participants provide a retrospective estimate of the number of drinks per week for the last seven days.	baseline, week 4
Change in Alcohol Craving as Assessed by Self Report Using the The Penn Alcohol Craving Scale (PACS).	The Penn Alcohol Craving Scale (PACS) is a 5-item questionnaire that measures an individual's craving to drink alcohol in the past week. Each item is scored on a scale from 0 to 6, with a total score range of 0 to 30. A higher score indicates greater level of alcohol craving.	baseline, week 4

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Investigators: Principal Investigator: Jin H Yoon, PhD, The University of Texas Health Science Center, Houston

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2019
• Primary Completion (Actual): August 23, 2019
• Study Completion (Actual): August 23, 2019

Study Registration Dates

• First Submitted: February 28, 2019
• First Submitted That Met QC Criteria: February 28, 2019
• First Posted (Actual): March 4, 2019

Study Record Updates

• Last Update Posted (Actual): October 26, 2020
• Last Update Submitted That Met QC Criteria: October 1, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Anxiety; Stress; Alcohol; Pioglitazone
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Alcoholism; Hypoglycemic Agents; Physiological Effects of Drugs; Pioglitazone
• Other Study ID Numbers: HSC-MS-18-0922 (pilot)

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