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

• Sponsor: The University of Texas Health Science Center, Houston (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03860753
• Collaborator: (none)
• Enrollment: 4
• Location: 1
• Arms: 2
• Actual Duration (Months): 5.7
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Alcohol Use Disorder	Drug: Pioglitazone; Drug: Placebo	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Effects of Pioglitazone on Stress Reactivity and Alcohol Craving (Pilot)
• Actual Study Start Date: Mar 1, 2019
• Actual Primary Completion Date: Aug 23, 2019
• Actual Study Completion Date: Aug 23, 2019

Arms and Interventions

Arm	Intervention/Treatment
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.
Placebo Comparator: Placebo	Drug: Placebo; Pill capsules will look same as that of active drug.

Outcome Measures

Primary Outcome Measures

1. Change in Stress-reactivity as Assessed by Heart Rate Change During the Cold Pressor Task (CPT) [baseline, week 4]

   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.

2. Change in Stress-reactivity as Assessed by Change in Systolic Blood Pressure During the Cold Pressor Task (CPT) [baseline, week 4]

   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.

3. Change in Stress-reactivity as Assessed by Diastolic Blood Pressure Change During the Cold Pressor Task (CPT) [baseline, week 4]

   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.

4. Change in Stress-reactivity as Assessed by Salivary Cortisol Level Change During the Cold Pressor Task (CPT) [baseline, week 4]

   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.

5. Change in Stress-reactivity as Assessed by Self-report on a Visual Analogue Scale (VAS) [baseline, week 4]

   The visual analogue scale (VAS) ranges from 0-10, with a higher score indicating higher stress.

Secondary Outcome Measures

1. Change in Alcohol Use as Indicated by Self Report Using the Alcohol Timeline Followback (TLFB) [baseline, week 4]

   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.

2. Change in Alcohol Craving as Assessed by Self Report Using the The Penn Alcohol Craving Scale (PACS). [baseline, week 4]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 40 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Texas Health Science at Houston	Houston	Texas	United States	77030

Sponsors and Collaborators

• The University of Texas Health Science Center, Houston

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 8, 2019

More Information

Publications

None provided.

• Responsible Party: Jin Ho Yoon, Assistant Professor, The University of Texas Health Science Center, Houston
• ClinicalTrials.gov Identifier: NCT03860753
• Other Study ID Numbers: HSC-MS-18-0922 (pilot)
• First Posted: Mar 4, 2019
• Last Update Posted: Oct 26, 2020
• Last Verified: Oct 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Keywords provided by Jin Ho Yoon, Assistant Professor, The University of Texas Health Science Center, Houston: Alcohol; Pioglitazone; Stress; Anxiety
• Additional relevant MeSH terms: Alcoholism; Pioglitazone

Study Results

Participant Flow

Arm/Group Title	Pioglitazone	Placebo
Arm/Group Description	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.	Placebo: Pill capsules will look same as that of active drug.
Period Title: Overall Study
STARTED	4	0
COMPLETED	4	0
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Pioglitazone	Placebo	Total
Arm/Group Description	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.	Placebo: Pill capsules will look same as that of active drug.	Total of all reporting groups
Overall Participants	4	0	4
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30.5 (5.20)	30.5 (5.20)
Sex: Female, Male (Count of Participants)
Female	1 25%	0 NaN	1 25%
Male	3 75%	0 NaN	3 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 25%	0 NaN	1 25%
Not Hispanic or Latino	3 75%	0 NaN	3 75%
Unknown or Not Reported	0 0%	0 NaN	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 NaN	0 0%
Asian	0 0%	0 NaN	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 NaN	0 0%
Black or African American	2 50%	0 NaN	2 50%
White	2 50%	0 NaN	2 50%
More than one race	0 0%	0 NaN	0 0%
Unknown or Not Reported	0 0%	0 NaN	0 0%
Region of Enrollment (Count of Participants)
United States	4 100%	0 NaN	4 100%

Outcome Measures

1. Primary Outcome

Title	Change in Stress-reactivity as Assessed by Heart Rate Change During the Cold Pressor Task (CPT)
Description	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.
Time Frame	baseline, week 4

Outcome Measure Data

Analysis Population Description

All 4 participants were allocated to Pioglitazone and none to placebo.

Arm/Group Title	Pioglitazone	Placebo
Arm/Group Description	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.	Placebo: Pill capsules will look same as that of active drug.
Measure Participants	4	0
Mean (Standard Deviation) [beats per minute]	-4.67 (11.60)

2. Primary Outcome

Title	Change in Stress-reactivity as Assessed by Change in Systolic Blood Pressure During the Cold Pressor Task (CPT)
Description	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.
Time Frame	baseline, week 4

Outcome Measure Data

Analysis Population Description

All 4 participants were allocated to Pioglitazone and none to placebo.

Arm/Group Title	Pioglitazone	Placebo
Arm/Group Description	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.	Placebo: Pill capsules will look same as that of active drug.
Measure Participants	4	0
Mean (Standard Deviation) [millimeters of mercury (mmHg)]	-2.67 (0.58)

3. Primary Outcome

Title	Change in Stress-reactivity as Assessed by Diastolic Blood Pressure Change During the Cold Pressor Task (CPT)
Description	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.
Time Frame	baseline, week 4

Outcome Measure Data

Analysis Population Description

All 4 participants were allocated to Pioglitazone and none to placebo.

Arm/Group Title	Pioglitazone	Placebo
Arm/Group Description	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.	Placebo: Pill capsules will look same as that of active drug.
Measure Participants	4	0
Mean (Standard Deviation) [millimeters of mercury (mmHg)]	-7.67 (8.08)

4. Primary Outcome

Title	Change in Stress-reactivity as Assessed by Salivary Cortisol Level Change During the Cold Pressor Task (CPT)
Description	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.
Time Frame	baseline, week 4

Outcome Measure Data

Analysis Population Description

All 4 participants were allocated to Pioglitazone and none to placebo.

Arm/Group Title	Pioglitazone	Placebo
Arm/Group Description	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.	Placebo: Pill capsules will look same as that of active drug.
Measure Participants	4	0
Mean (Standard Deviation) [picograms per milliliter (pg/mL)]	-108.07 (830.46)

5. Primary Outcome

Title	Change in Stress-reactivity as Assessed by Self-report on a Visual Analogue Scale (VAS)
Description	The visual analogue scale (VAS) ranges from 0-10, with a higher score indicating higher stress.
Time Frame	baseline, week 4

Outcome Measure Data

Analysis Population Description

All 4 participants were allocated to Pioglitazone and none to placebo.

Arm/Group Title	Pioglitazone	Placebo
Arm/Group Description	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.	Placebo: Pill capsules will look same as that of active drug.
Measure Participants	4	0
Mean (Standard Deviation) [units on a scale]	-1.33 (1.53)

6. Secondary Outcome

Title	Change in Alcohol Use as Indicated by Self Report Using the Alcohol Timeline Followback (TLFB)
Description	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.
Time Frame	baseline, week 4

Outcome Measure Data

Analysis Population Description

All 4 participants were allocated to Pioglitazone and none to placebo.

Arm/Group Title	Pioglitazone	Placebo
Arm/Group Description	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.	Placebo: Pill capsules will look same as that of active drug.
Measure Participants	4	0
Mean (Standard Deviation) [number of drinks per week]	-13.38 (11.22)

7. Secondary Outcome

Title	Change in Alcohol Craving as Assessed by Self Report Using the The Penn Alcohol Craving Scale (PACS).
Description	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.
Time Frame	baseline, week 4

Outcome Measure Data

Analysis Population Description

All 4 participants were allocated to Pioglitazone and none to placebo.

Arm/Group Title	Pioglitazone	Placebo
Arm/Group Description	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.	Placebo: Pill capsules will look same as that of active drug.
Measure Participants	4	0
Mean (Standard Deviation) [score on a scale]	-8.5 (6.6)

Adverse Events

Time Frame	4 weeks
Adverse Event Reporting Description	All 4 participants were allocated to Pioglitazone and none to placebo.
Arm/Group Title	Pioglitazone		Placebo
Arm/Group Description	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.		Placebo: Pill capsules will look same as that of active drug.
All Cause Mortality
	Pioglitazone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/0 (NaN)
Serious Adverse Events
	Pioglitazone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Pioglitazone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/4 (50%)		0/0 (NaN)
General disorders
weight gain	2/4 (50%)	2	0/0 (NaN)	0
right ankle stiffness	1/4 (25%)	1	0/0 (NaN)	0

Limitations/Caveats

Early termination leading to small numbers of subjects analyzed.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.