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

Study Overview
=================
Brief Summary
-----------------
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.

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

Conditions
-----------------
Alcohol Use Disorder

Intervention / Treatment
-----------------
* Drug: Pioglitazone
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


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 week 2, 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?
-----------------
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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Alcohol, Pioglitazone, Stress, Anxiety