Influence of n-Acetylcysteine Maintenance on Alcohol Effects

• Sponsor: William Stoops (Other)
• Overall Status: Completed
• CT.gov ID: NCT03216954
• Collaborator: National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH)
• Enrollment: 14
• Location: 1
• Arms: 3
• Actual Duration (Months): 31.2
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This study will evaluate the behavioral effects of alcohol during placebo and n-acetylcysteine maintenance using sophisticated human laboratory methods.

Condition or Disease	Intervention/Treatment	Phase
Alcohol Use Disorder	Drug: Alcohol; Drug: Placebos; Drug: N-acetyl cysteine	Early Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: A Human Laboratory Study of n-Acetylcysteine for Alcohol Use Disorder
• Actual Study Start Date: Sep 15, 2017
• Actual Primary Completion Date: Apr 23, 2020
• Actual Study Completion Date: Apr 23, 2020

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Subjects will receive oral placebo capsules two times daily.	Drug: Alcohol; During each arm, subjects will receive doses of alcohol, designed to raise BALs to 0.015 and 0.03 g/dl.; Drug: Placebos; Subjects will receive placebo capsules
Experimental: Low Dose n-Acetylcysteine Subjects will receive 0.6 g oral n-acetylcysteine two times daily.	Drug: Alcohol; During each arm, subjects will receive doses of alcohol, designed to raise BALs to 0.015 and 0.03 g/dl.; Drug: N-acetyl cysteine; Subjects will receive n-acetyl cysteine capsules
Experimental: High Dose n-Acetylcysteine Subjects will receive 1.2 g oral n-acetylcysteine two times daily.	Drug: Alcohol; During each arm, subjects will receive doses of alcohol, designed to raise BALs to 0.015 and 0.03 g/dl.; Drug: N-acetyl cysteine; Subjects will receive n-acetyl cysteine capsules

Outcome Measures

Primary Outcome Measures

1. Number of Alcohol Drinks Chosen [After at least four days of placebo or n-acetylcysteine maintenance]

   The reinforcing effects of alcohol were determined using a self-administration procedure in which subjects choose to take previously sampled doses. Reinforcing effects are measured during maintenance on placebo and n-acetylcysteine.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• able to speak/read English

• not seeking treatment at the time of the study

• one binge drinking episode (5+/4+ standard alcoholic drinks per drinking session for men and women, respectively) in the past 30 days

• recent alcohol use verified by ethyl glucuronide positive urine, as well as fulfillment of DSM-5 diagnostic criteria for alcohol use disorder

• ECG within normal limits

• otherwise healthy

• body mass index of 19-35

• females using an effective form of birth control and not pregnant or breast feeding

• judged by the medical staff to be psychiatrically and physically healthy

• able to abstain from alcohol for 12 hours prior to session

• no contraindications/allergies to n-acetylcysteine

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Kentucky	Lexington	Kentucky	United States	40507

Sponsors and Collaborators

• William Stoops
• National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

• Principal Investigator: William W Stoops, PhD, University of Kentucky

Study Documents (Full-Text)

• Informed Consent Form - Mar 3, 2020
• Study Protocol and Statistical Analysis Plan - Dec 15, 2020

More Information

Publications

None provided.

• Responsible Party: William Stoops, Professor, University of Kentucky
• ClinicalTrials.gov Identifier: NCT03216954
• Other Study ID Numbers: BED IN 34; R21AA026129
• First Posted: Jul 13, 2017
• Last Update Posted: Jan 26, 2021
• Last Verified: Jan 1, 2021

• 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.: Yes
• Additional relevant MeSH terms: Alcoholism; Alcohol Drinking; Acetylcysteine; N-monoacetylcystine

Study Results

Participant Flow

Arm/Group Title	Placebo Then 1.2 g n-Acetylcysteine Then 2.4 g n-Acetylcysteine	2.4 g n-Acetylcysteine Then 1.2 g n-Acetylcysteine Then Placebo	Placebo Then 2.4 g n-Acetylcysteine Then 1.2 g n-Acetylcysteine	1.2 g n-Acetylcysteine Then Placebo Then 2.4 g n-Acetylcysteine	1.2 g n-Acetylcysteine Then 2.4 g n-Acetylcysteine Then Placebo
Arm/Group Description	Subjects were maintained on placebo for 5 days, then they were maintained on 1.2 g n-acetylcysteine daily for 5 days, then they were maintained on 2.4 g n-acetylcysteine for 5 days.	Subjects were maintained on 2.4 g n-acetylcysteine for 5 days, then they were maintained on 1.2 g n-acetylcysteine daily for 5 days, then they were maintained on placebo for 5 days.	Subjects were maintained on placebo for 5 days, then they were maintained on 2.4 g n-acetylcysteine, then they were maintained on 1.2 g n-acetylcysteine.	Subjects were maintained on 1.2 g n-acetylcysteine for 5 days, then they were maintained on placebo for 5 days, then they were maintained on 2.4 g n-acetylcysteine for 5 days.	Subjects were maintained on 1.2 g n-acetylcysteine for 5 days then they were maintained on 2.4 g n-acetylcysteine for 5 days, then they were maintained on placebo.
Period Title: Overall Study
STARTED	4	3	3	3	1
COMPLETED	2	2	2	3	0
NOT COMPLETED	2	1	1	0	1

Baseline Characteristics

Arm/Group Title	Crossover Study Drug Conditions
Arm/Group Description	Subjects received oral placebo, 0.6 g n-acetylcysteine or 1.2 g n-acetylcysteine capsules two times daily. Dose condition was assigned in random order and all completing subjects received all dose conditions. Alcohol: During each condition, subjects received doses of alcohol, designed to raise BALs to 0.015 and 0.03 g/dl. Placebos: Subjects received placebo capsules. n-Acetylcysteine: Subjects received n-acetylcysteine capsules.
Overall Participants	9
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	29 (4)
Sex: Female, Male (Count of Participants)
Female	4 44.4%
Male	5 55.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 22.2%
White	6 66.7%
More than one race	1 11.1%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	9 100%

Outcome Measures

1. Primary Outcome

Title	Number of Alcohol Drinks Chosen
Description	The reinforcing effects of alcohol were determined using a self-administration procedure in which subjects choose to take previously sampled doses. Reinforcing effects are measured during maintenance on placebo and n-acetylcysteine.
Time Frame	After at least four days of placebo or n-acetylcysteine maintenance

Outcome Measure Data

Analysis Population Description

Completing Subjects

Arm/Group Title	Placebo	Low Dose n-Acetylcysteine	High Dose n-Acetylcysteine
Arm/Group Description	Subjects received oral placebo capsules two times daily. Alcohol: During each arm, subjects will receive doses of alcohol, designed to raise BALs to 0.015 and 0.03 g/dl. Placebos: Subjects will receive placebo capsules	Subjects received 0.6 g oral n-acetylcysteine two times daily. Alcohol: During each arm, subjects will receive doses of alcohol, designed to raise BALs to 0.015 and 0.03 g/dl. N-acetyl cysteine: Subjects will receive n-acetyl cysteine capsules	Subjects received 1.2 g oral n-acetylcysteine two times daily. Alcohol: During each arm, subjects will receive doses of alcohol, designed to raise BALs to 0.015 and 0.03 g/dl. N-acetyl cysteine: Subjects will receive n-acetyl cysteine capsules
Measure Participants	9	9	9
Mean (Standard Deviation) [Number of Alcohol Drinks Chosen]	3.1 (3.5)	2.8 (3.5)	3.8 (3.6)

Adverse Events

Time Frame	Full duration of each subject's participation, approximately 5 weeks.
Arm/Group Title	Placebo Maintenance		1.2 g n-Acetylcysteine Maintenance		2.4 g n-Acetylcysteine Maintenance
Arm/Group Description	Subjects received oral placebo capsules two times daily. Alcohol: During each arm, subjects will receive doses of alcohol, designed to raise BALs to 0.015 and 0.03 g/dl. Placebos: Subjects received placebo capsules		Subjects received 0.6 g n-acetylcysteine capsules two times daily. Alcohol: During each arm, subjects will receive doses of alcohol, designed to raise BALs to 0.015 and 0.03 g/dl. Placebos: Subjects received placebo capsules n-Acetylcysteine: Subjects received 0.6 g n-acetylcysteine capsules		Subjects received 1.2 g n-acetylcysteine capsules two times daily. Alcohol: During each arm, subjects will receive doses of alcohol, designed to raise BALs to 0.015 and 0.03 g/dl. Placebos: Subjects received placebo capsules n-Acetylcysteine: Subjects received 1.2 g n-acetylcysteine capsules
All Cause Mortality
	Placebo Maintenance		1.2 g n-Acetylcysteine Maintenance		2.4 g n-Acetylcysteine Maintenance
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/14 (0%)		0/14 (0%)
Serious Adverse Events
	Placebo Maintenance		1.2 g n-Acetylcysteine Maintenance		2.4 g n-Acetylcysteine Maintenance
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/14 (0%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	Placebo Maintenance		1.2 g n-Acetylcysteine Maintenance		2.4 g n-Acetylcysteine Maintenance
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/14 (7.1%)		1/14 (7.1%)		0/14 (0%)
Eye disorders
Blurry vision	0/14 (0%)	0	1/14 (7.1%)	1	0/14 (0%)	0
Gastrointestinal disorders
Nausea	1/14 (7.1%)	1	0/14 (0%)	0	0/14 (0%)	0
Vomiting	1/14 (7.1%)	1	0/14 (0%)	0	0/14 (0%)	0
General disorders
Thirst	0/14 (0%)	0	1/14 (7.1%)	1	0/14 (0%)	0
Nervous system disorders
Dizziness	0/14 (0%)	0	1/14 (7.1%)	1	0/14 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.