Effects of Pioglitazone on Stress Reactivity and Alcohol Craving

Study Overview
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Brief Summary
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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

Official Title
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Effects of Pioglitazone on Stress Reactivity and Alcohol Craving

Conditions
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Alcohol Use Disorder

Intervention / Treatment
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* Drug: Pioglitazone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pioglitazone<br> | Drug: Pioglitazone<br>* 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.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Pill capsules will look same as that of active drug.<br>|

What is the study measuring?
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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) |  | baseline,week 8 | 
| Change in Stress-reactivity as Assessed by Change in Systolic Blood Pressure During the Cold Pressor Task (CPT) |  | baseline,week 8 | 
| Change in Stress-reactivity as Assessed by Diastolic Blood Pressure Change During the Cold Pressor Task (CPT)Cold Pressor Task (CPT) |  | baseline,week 8 | 
| Change in Stress-reactivity as Assessed by Salivary Cortisol Level Change During the Cold Pressor Task (CPT) |  | baseline,week 8 | 
| Change in alcohol craving | This self report assessment will be based on the human laboratory stress reactivity assessment and will be measured by the Alcohol craving scale which is a 5 item questionnaire and each item is scored form 0( none)- 10 (extreme) a higher number indicating a higher alcohol craving with a maximum score of 50. | baseline,week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in drinking habit as assessed by the number of drinks per day |  | baseline to week 8 | 
| change in drinking habit as assessed by the number of heavy drinking days |  | baseline to week 8 | 
| Stress as assessed by the Perceived Stress Scale(PSS) | This self report scale is a 10 item questionnaire and is scored form 0(never)-4( very often) for a maximum score of 40 | Baseline, week 1,week 2,week3,week 4,week 5,week 6, week 7,week 8 | 
| Anxiety as assessed by the Hamilton Anxiety Rating Scale(HAM-A) | This self report scale is a 14 item questionnaire scored form 0(not present) to 4 (very severe) with a maximum score of 56 | Baseline, week 1,week 2,week3,week 4,week 5,week 6, week 7,week 8 | 
| Change in alcohol craving as assessed by the Pennsylvania Alcohol Craving Scale(PACS) | The PACS is a five-item self-administered instrument for assessing craving. Frequency, intensity, and duration of thoughts about drinking are assessed along with ability to resist drinking. The final item asks the responder to provide an average rating of his/her craving over the course of the past week. Each item is scored from 0(none)-10(extreme), a higher number indicating more craving. | baseline,week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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alcohol, Pioglitazone, Stress, Anxiety