Trial Outcomes & Findings for Effects of Pioglitazone on Stress Reactivity and Alcohol Craving (NCT NCT05107765)

NCT ID: NCT05107765

Last Updated: 2025-08-27

Results Overview

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 \[(Heart rate post cold pressor task) - (Heart rate pre cold pressor task)\].

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 67 participants
• Primary outcome timeframe: Baseline, about 2 minutes after the start of the cold pressor task
• Results posted on: 2025-08-27

Participant Flow

Of the 67 participants enrolled, 55 were randomized; 8 were lost to follow-up before randomization, and 4 withdrew before randomization.

Participant milestones

Measure	Placebo Placebo: Pill capsules will look same as that of active drug.	Pioglitazone 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Overall Study STARTED	29	26
Overall Study COMPLETED	18	22
Overall Study NOT COMPLETED	11	4

Reasons for withdrawal

Measure	Placebo Placebo: Pill capsules will look same as that of active drug.	Pioglitazone 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Overall Study Lost to Follow-up	4	1
Overall Study Withdrawn by investigator due to non-compliance	1	0
Overall Study Withdrawal by Subjects due to scheduling issues	6	3

Baseline Characteristics

Effects of Pioglitazone on Stress Reactivity and Alcohol Craving

Baseline characteristics by cohort

Measure	Placebo n=29 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=26 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.	Total n=55 Participants Total of all reporting groups
Age, Continuous	38.03 years STANDARD_DEVIATION 13.63 • n=93 Participants	33.58 years STANDARD_DEVIATION 10.26 • n=4 Participants	35.93 years STANDARD_DEVIATION 12.36 • n=27 Participants
Sex: Female, Male Female	17 Participants n=93 Participants	16 Participants n=4 Participants	33 Participants n=27 Participants
Sex: Female, Male Male	12 Participants n=93 Participants	10 Participants n=4 Participants	22 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=93 Participants	9 Participants n=4 Participants	19 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=93 Participants	17 Participants n=4 Participants	36 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	5 Participants n=93 Participants	1 Participants n=4 Participants	6 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	5 Participants n=93 Participants	8 Participants n=4 Participants	13 Participants n=27 Participants
Race (NIH/OMB) White	17 Participants n=93 Participants	15 Participants n=4 Participants	32 Participants n=27 Participants
Race (NIH/OMB) More than one race	2 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants
Region of Enrollment United States	29 participants n=93 Participants	26 participants n=4 Participants	55 participants n=27 Participants
Years of Education	15.38 years STANDARD_DEVIATION 1.92 • n=93 Participants	15.92 years STANDARD_DEVIATION 2.9 • n=4 Participants	15.64 years STANDARD_DEVIATION 2.12 • n=27 Participants

PRIMARY outcome

Timeframe: Baseline, about 2 minutes after the start of the cold pressor task

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)].

Outcome measures

Measure	Placebo n=29 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=26 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Change in Stress-reactivity as Assessed by Heart Rate Change During the Cold Pressor Task (CPT)	5.138 beats per minutes (bpm) Standard Deviation 11.426	12.154 beats per minutes (bpm) Standard Deviation 11.885

PRIMARY outcome

Timeframe: Week 8, about 2 minutes after the start of the Cold Pressor Task

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)].

Outcome measures

Measure	Placebo n=18 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=22 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Change in Stress-reactivity as Assessed by Heart Rate Change During the Cold Pressor Task (CPT)	4.444 beats per minutes (bpm) Standard Deviation 8.118	11.182 beats per minutes (bpm) Standard Deviation 12.945

PRIMARY outcome

Timeframe: Baseline, about 2 minutes after the start of the Cold Pressor Task

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)].

Outcome measures

Measure	Placebo n=29 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=26 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Change in Stress-reactivity as Assessed by Change in Systolic Blood Pressure During the Cold Pressor Task (CPT)	19.931 millimeters of mercury (mmHg) Standard Deviation 12.236	20.038 millimeters of mercury (mmHg) Standard Deviation 13.721

PRIMARY outcome

Timeframe: Week 8, about 2 minutes after the start of the Cold Pressor Task

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)].

Outcome measures

Measure	Placebo n=18 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=22 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Change in Stress-reactivity as Assessed by Change in Systolic Blood Pressure During the Cold Pressor Task (CPT)	17.778 millimeters of mercury (mmHg) Standard Deviation 10.963	21.091 millimeters of mercury (mmHg) Standard Deviation 15.165

PRIMARY outcome

Timeframe: Baseline, about 2 minutes after the start of the Cold Pressor Task

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)].

Outcome measures

Measure	Placebo n=29 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=26 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Change in Stress-reactivity as Assessed by Diastolic Blood Pressure Change During the Cold Pressor Task (CPT)Cold Pressor Task (CPT)	12.793 millimeters of mercury (mmHg) Standard Deviation 8.862	13.192 millimeters of mercury (mmHg) Standard Deviation 10.257

PRIMARY outcome

Timeframe: Week 8, about 2 minutes after the start of the Cold Pressor Task

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)].

Outcome measures

Measure	Placebo n=18 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=22 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Change in Stress-reactivity as Assessed by Diastolic Blood Pressure Change During the Cold Pressor Task (CPT)Cold Pressor Task (CPT)	12 millimeters of mercury (mmHg) Standard Deviation 9.911	13.545 millimeters of mercury (mmHg) Standard Deviation 10.613

PRIMARY outcome

Timeframe: baseline, about 32 minutes after the start of the Cold Pressor Task

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)].

Outcome measures

Measure	Placebo n=29 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=26 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Change in Stress-reactivity as Assessed by Salivary Cortisol Level Change During the Cold Pressor Task (CPT)	230.087 picograms per milliliter (pg/mL) Standard Deviation 1040.858	908.96 picograms per milliliter (pg/mL) Standard Deviation 2046.185

PRIMARY outcome

Timeframe: week 8, about 32 minutes after the start of the Cold Pressor Task

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)].

Outcome measures

Measure	Placebo n=18 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=22 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Change in Stress-reactivity as Assessed by Salivary Cortisol Level Change During the Cold Pressor Task (CPT)	427.61 picograms per milliliter (pg/mL) Standard Deviation 917.927	447.417 picograms per milliliter (pg/mL) Standard Deviation 1466.214

PRIMARY outcome

Timeframe: baseline, about 2 minutes after the start of the 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.

Outcome measures

Measure	Placebo n=29 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=26 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Change in Alcohol Craving as Assessed by Alcohol Craving Scale Score During the Cold Pressor Task (CPT)	-0.083 score on a scale Standard Deviation 1.36	0.092 score on a scale Standard Deviation 1.877

PRIMARY outcome

Timeframe: week 8, about 2 minutes after the start of the 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.

Outcome measures

Measure	Placebo n=18 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=22 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Change in Alcohol Craving as Assessed by Alcohol Craving Scale Score During the Cold Pressor Task (CPT)	0.367 score on a scale Standard Deviation 0.963	1.173 score on a scale Standard Deviation 2.196

SECONDARY outcome

Timeframe: baseline, week 8

The Timeline Followback (TLFB) method was used to assess alcohol consumption by asking study participants to self-report their number of drinks consumed each day over the past week.

The change in drinking habit is reported as [(number of drinks per day at week 8) - (number of drinks per day at baseline)].-- a negative value indicates a decrease in alcohol consumption over time.

Outcome measures

Measure	Placebo n=18 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=22 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Change in Drinking Habit as Assessed by the Number of Drinks Per Day (Timeline Followback Method)	-1.229 drinks per day Standard Deviation 1.49	-0.714 drinks per day Standard Deviation 1.02

SECONDARY outcome

Timeframe: baseline, week 8

The Timeline Followback (TLFB) method was used to assess alcohol consumption by asking study participants to self-report their number of drinks consumed each day over the past week.

Heavy drinking is defined as 4 drinks or more per day for females and 5 or more drinks per day for males. The change in drinking habit is reported as [(number of heavy drinking days at week 8) - (number of heavy drinking days at baseline)].--A negative value indicates a decrease in the number of heavy drinking days over time.

Outcome measures

Measure	Placebo n=18 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=22 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Change in Drinking Habit as Assessed by the Number of Heavy Drinking Days (Timeline Followback Method)	-5.5 Heavy drinking days Standard Deviation 5.113	-3.591 Heavy drinking days Standard Deviation 4.152

SECONDARY outcome

Timeframe: Baseline

The Hamilton Anxiety Rating Scale(HAM-A) is a 14 item questionnaire scored from 0 (not present) to 4 (very severe). The 14 items are summed to obtain a total score ranging from 0 to 56, high scores indicating greater anxiety.

Outcome measures

Measure	Placebo n=29 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=26 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)	5.862 score on a scale Standard Deviation 4.991	4 score on a scale Standard Deviation 3.929

SECONDARY outcome

Timeframe: week 1

Population: Data were only collected from participants who completed the survey.

The Hamilton Anxiety Rating Scale(HAM-A) is a 14 item questionnaire scored from 0 (not present) to 4 (very severe). The 14 items are summed to obtain a total score ranging from 0 to 56, high scores indicating greater anxiety.

Outcome measures

Measure	Placebo n=24 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=24 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)	5.458 score on a scale Standard Deviation 5.141	3.458 score on a scale Standard Deviation 3.538

SECONDARY outcome

Timeframe: week 2

Population: Data were only collected from participants who completed the survey.

The Hamilton Anxiety Rating Scale(HAM-A) is a 14 item questionnaire scored from 0 (not present) to 4 (very severe). The 14 items are summed to obtain a total score ranging from 0 to 56, high scores indicating greater anxiety.

Outcome measures

Measure	Placebo n=23 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=23 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)	4.087 score on a scale Standard Deviation 4.01	3.435 score on a scale Standard Deviation 3.116

SECONDARY outcome

Timeframe: week 3

Population: Data were only collected from participants who completed the survey.

The Hamilton Anxiety Rating Scale(HAM-A) is a 14 item questionnaire scored from 0 (not present) to 4 (very severe). The 14 items are summed to obtain a total score ranging from 0 to 56, high scores indicating greater anxiety.

Outcome measures

Measure	Placebo n=22 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=21 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)	4.727 score on a scale Standard Deviation 4.143	2.95 score on a scale Standard Deviation 3.236

SECONDARY outcome

Timeframe: week 4

Population: Data were only collected from participants who completed the survey.

The Hamilton Anxiety Rating Scale(HAM-A) is a 14 item questionnaire scored from 0 (not present) to 4 (very severe). The 14 items are summed to obtain a total score ranging from 0 to 56, high scores indicating greater anxiety.

Outcome measures

Measure	Placebo n=20 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=21 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)	4.1 score on a scale Standard Deviation 4.291	2.524 score on a scale Standard Deviation 4.308

SECONDARY outcome

Timeframe: week 5

Population: Data were only collected from participants who completed the survey.

The Hamilton Anxiety Rating Scale(HAM-A) is a 14 item questionnaire scored from 0 (not present) to 4 (very severe). The 14 items are summed to obtain a total score ranging from 0 to 56, high scores indicating greater anxiety.

Outcome measures

Measure	Placebo n=20 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=22 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)	3.45 score on a scale Standard Deviation 4.019	2.5 score on a scale Standard Deviation 2.502

SECONDARY outcome

Timeframe: week 6

Population: Data were only collected from participants who completed the survey.

The Hamilton Anxiety Rating Scale(HAM-A) is a 14 item questionnaire scored from 0 (not present) to 4 (very severe). The 14 items are summed to obtain a total score ranging from 0 to 56, high scores indicating greater anxiety.

Outcome measures

Measure	Placebo n=20 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=21 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)	2.895 score on a scale Standard Deviation 3.053	2.6 score on a scale Standard Deviation 3.662

SECONDARY outcome

Timeframe: week 7

Population: Data were only collected from participants who completed the survey.

The Hamilton Anxiety Rating Scale(HAM-A) is a 14 item questionnaire scored from 0 (not present) to 4 (very severe). The 14 items are summed to obtain a total score ranging from 0 to 56, high scores indicating greater anxiety.

Outcome measures

Measure	Placebo n=20 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=22 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)	2.842 score on a scale Standard Deviation 2.566	3.364 score on a scale Standard Deviation 5.876

SECONDARY outcome

Timeframe: week 8

The Hamilton Anxiety Rating Scale(HAM-A) is a 14 item questionnaire scored from 0 (not present) to 4 (very severe). The 14 items are summed to obtain a total score ranging from 0 to 56, high scores indicating greater anxiety.

Outcome measures

Measure	Placebo n=18 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=22 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Anxiety as Assessed by the Hamilton Anxiety Rating Scale(HAM-A)	4.167 score on a scale Standard Deviation 3.869	2.952 score on a scale Standard Deviation 4.226

SECONDARY outcome

Timeframe: baseline

The Pennsylvania Alcohol Craving Scale(PACS) total score ranges from 0 to 30, higher scores indicating more alcohol cravings.

Outcome measures

Measure	Placebo n=29 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=26 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Alcohol Craving as Assessed by the Pennsylvania Alcohol Craving Scale(PACS)	11.103 score on a scale Standard Deviation 4.678	9.577 score on a scale Standard Deviation 5.994

SECONDARY outcome

Timeframe: Week 8

The Pennsylvania Alcohol Craving Scale(PACS) total score ranges from 0 to 30, higher scores indicating more alcohol cravings.

Outcome measures

Measure	Placebo n=18 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=22 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Alcohol Craving as Assessed by the Pennsylvania Alcohol Craving Scale(PACS)	5.6111 score on a scale Standard Deviation 5.6375	7.409 score on a scale Standard Deviation 5.981

SECONDARY outcome

Timeframe: Baseline

The Perceived Stress Scale(PSS) is a 10 item questionnaire scored from 0 (never) to 4 (very often). The 10 items are summed to obtain a total score ranging from 0 to 40, high scores indicating greater stress.

Outcome measures

Measure	Placebo n=29 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=26 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Stress as Assessed by the Perceived Stress Scale(PSS)	14.276 score on a scale Standard Deviation 7.892	12.808 score on a scale Standard Deviation 7.731

SECONDARY outcome

Timeframe: Week 1

Population: Data were only collected from participants who completed the survey.

The Perceived Stress Scale(PSS) is a 10 item questionnaire scored from 0 (never) to 4 (very often). The 10 items are summed to obtain a total score ranging from 0 to 40, high scores indicating greater stress.

Outcome measures

Measure	Placebo n=24 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=24 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Stress as Assessed by the Perceived Stress Scale(PSS)	15.208 score on a scale Standard Deviation 7.407	14.583 score on a scale Standard Deviation 6.928

SECONDARY outcome

Timeframe: Week 2

Population: Data were only collected from participants who completed the survey.

The Perceived Stress Scale(PSS) is a 10 item questionnaire scored from 0 (never) to 4 (very often). The 10 items are summed to obtain a total score ranging from 0 to 40, high scores indicating greater stress.

Outcome measures

Measure	Placebo n=23 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=23 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Stress as Assessed by the Perceived Stress Scale(PSS)	13.522 score on a scale Standard Deviation 7.988	14.783 score on a scale Standard Deviation 6.915

SECONDARY outcome

Timeframe: Week 3

Population: Data were only collected from participants who completed the survey.

The Perceived Stress Scale(PSS) is a 10 item questionnaire scored from 0 (never) to 4 (very often). The 10 items are summed to obtain a total score ranging from 0 to 40, high scores indicating greater stress.

Outcome measures

Measure	Placebo n=22 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=21 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Stress as Assessed by the Perceived Stress Scale(PSS)	13.318 score on a scale Standard Deviation 6.785	14.19 score on a scale Standard Deviation 8.116

SECONDARY outcome

Timeframe: Week 4

Population: Data were only collected from participants who completed the survey.

The Perceived Stress Scale(PSS) is a 10 item questionnaire scored from 0 (never) to 4 (very often). The 10 items are summed to obtain a total score ranging from 0 to 40, high scores indicating greater stress.

Outcome measures

Measure	Placebo n=20 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=21 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Stress as Assessed by the Perceived Stress Scale(PSS)	12.65 score on a scale Standard Deviation 9.08	14.143 score on a scale Standard Deviation 6.24

SECONDARY outcome

Timeframe: Week 5

Population: Data were only collected from participants who completed the survey.

The Perceived Stress Scale(PSS) is a 10 item questionnaire scored from 0 (never) to 4 (very often). The 10 items are summed to obtain a total score ranging from 0 to 40, high scores indicating greater stress.

Outcome measures

Measure	Placebo n=20 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=22 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Stress as Assessed by the Perceived Stress Scale(PSS)	12.55 score on a scale Standard Deviation 8.787	12.227 score on a scale Standard Deviation 7.237

SECONDARY outcome

Timeframe: Week 6

Population: Data were only collected from participants who completed the survey.

The Perceived Stress Scale(PSS) is a 10 item questionnaire scored from 0 (never) to 4 (very often). The 10 items are summed to obtain a total score ranging from 0 to 40, high scores indicating greater stress.

Outcome measures

Measure	Placebo n=20 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=21 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Stress as Assessed by the Perceived Stress Scale(PSS)	13.8 score on a scale Standard Deviation 6.478	12.429 score on a scale Standard Deviation 7.427

SECONDARY outcome

Timeframe: Week 7

Population: Data were only collected from participants who completed the survey.

The Perceived Stress Scale(PSS) is a 10 item questionnaire scored from 0 (never) to 4 (very often). The 10 items are summed to obtain a total score ranging from 0 to 40, high scores indicating greater stress.

Outcome measures

Measure	Placebo n=20 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=22 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Stress as Assessed by the Perceived Stress Scale(PSS)	11.7 score on a scale Standard Deviation 5.966	12.455 score on a scale Standard Deviation 8.629

SECONDARY outcome

Timeframe: Week 8

Population: Data were only collected from participants who completed the survey.

The Perceived Stress Scale(PSS) is a 10 item questionnaire scored from 0 (never) to 4 (very often). The 10 items are summed to obtain a total score ranging from 0 to 40, high scores indicating greater stress.

Outcome measures

Measure	Placebo n=18 Participants Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=22 Participants 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Stress as Assessed by the Perceived Stress Scale(PSS)	11.222 score on a scale Standard Deviation 7.224	12.318 score on a scale Standard Deviation 6.284

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 25 other events

Deaths: 0 deaths

Pioglitazone

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Placebo n=29 participants at risk Placebo: Pill capsules will look same as that of active drug.	Pioglitazone n=26 participants at risk 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 end of week 1, which is within standard titration parameters as per the investigator's brochure.
Nervous system disorders Drowsiness	41.4% 12/29 • Up to 8 weeks	42.3% 11/26 • Up to 8 weeks
Nervous system disorders Not Sleeping Well	44.8% 13/29 • Up to 8 weeks	46.2% 12/26 • Up to 8 weeks
Nervous system disorders Headache	27.6% 8/29 • Up to 8 weeks	42.3% 11/26 • Up to 8 weeks
Nervous system disorders Nervousness	6.9% 2/29 • Up to 8 weeks	7.7% 2/26 • Up to 8 weeks
Nervous system disorders Blurry Vision	17.2% 5/29 • Up to 8 weeks	3.8% 1/26 • Up to 8 weeks
Nervous system disorders Dizziness	13.8% 4/29 • Up to 8 weeks	11.5% 3/26 • Up to 8 weeks
Nervous system disorders Tremor	24.1% 7/29 • Up to 8 weeks	26.9% 7/26 • Up to 8 weeks
Nervous system disorders Sweating	20.7% 6/29 • Up to 8 weeks	11.5% 3/26 • Up to 8 weeks
Nervous system disorders Confusion	6.9% 2/29 • Up to 8 weeks	11.5% 3/26 • Up to 8 weeks
Nervous system disorders Cloudiness	10.3% 3/29 • Up to 8 weeks	23.1% 6/26 • Up to 8 weeks
Nervous system disorders Memory Loss	13.8% 4/29 • Up to 8 weeks	23.1% 6/26 • Up to 8 weeks
Nervous system disorders Fatigue Tiredness	3.4% 1/29 • Up to 8 weeks	0.00% 0/26 • Up to 8 weeks
Nervous system disorders Difficulty Walking	3.4% 1/29 • Up to 8 weeks	15.4% 4/26 • Up to 8 weeks
Nervous system disorders Weakness	17.2% 5/29 • Up to 8 weeks	19.2% 5/26 • Up to 8 weeks
Nervous system disorders Heart Racing	10.3% 3/29 • Up to 8 weeks	11.5% 3/26 • Up to 8 weeks
Nervous system disorders Chest pain	10.3% 3/29 • Up to 8 weeks	15.4% 4/26 • Up to 8 weeks
Gastrointestinal disorders Nausea	20.7% 6/29 • Up to 8 weeks	15.4% 4/26 • Up to 8 weeks
Gastrointestinal disorders Vomiting	10.3% 3/29 • Up to 8 weeks	15.4% 4/26 • Up to 8 weeks
Gastrointestinal disorders Constipation	20.7% 6/29 • Up to 8 weeks	34.6% 9/26 • Up to 8 weeks
Gastrointestinal disorders Diarrhea	10.3% 3/29 • Up to 8 weeks	30.8% 8/26 • Up to 8 weeks
Gastrointestinal disorders Stomach Cramps	31.0% 9/29 • Up to 8 weeks	26.9% 7/26 • Up to 8 weeks
Respiratory, thoracic and mediastinal disorders Shortness of Breath	17.2% 5/29 • Up to 8 weeks	34.6% 9/26 • Up to 8 weeks
Respiratory, thoracic and mediastinal disorders Cough	27.6% 8/29 • Up to 8 weeks	26.9% 7/26 • Up to 8 weeks
Renal and urinary disorders Increased Urination	17.2% 5/29 • Up to 8 weeks	15.4% 4/26 • Up to 8 weeks
Endocrine disorders Dry Mouth	34.5% 10/29 • Up to 8 weeks	53.8% 14/26 • Up to 8 weeks
Endocrine disorders Loss of appetite	3.4% 1/29 • Up to 8 weeks	7.7% 2/26 • Up to 8 weeks
Immune system disorders Fever or Chills	10.3% 3/29 • Up to 8 weeks	19.2% 5/26 • Up to 8 weeks
Immune system disorders skin rash	13.8% 4/29 • Up to 8 weeks	11.5% 3/26 • Up to 8 weeks
Musculoskeletal and connective tissue disorders Muscle Aches	17.2% 5/29 • Up to 8 weeks	19.2% 5/26 • Up to 8 weeks
Musculoskeletal and connective tissue disorders Elevated CK Levels	6.9% 2/29 • Up to 8 weeks	0.00% 0/26 • Up to 8 weeks
Blood and lymphatic system disorders Swelling	3.4% 1/29 • Up to 8 weeks	11.5% 3/26 • Up to 8 weeks
Reproductive system and breast disorders Change in Sexual Function	17.2% 5/29 • Up to 8 weeks	11.5% 3/26 • Up to 8 weeks

Additional Information

Jin H Yoon, PhD

The University of Texas Health Science Center of Houston

Phone: 713-486-2800

Email: jin.ho.yoon@uth.tmc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place