N-acetylcysteine for Tobacco Use Disorder

• Sponsor: Medical University of South Carolina (Other)
• Overall Status: Completed
• CT.gov ID: NCT02737358
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 114
• Location: 1
• Arms: 2
• Actual Duration (Months): 37.3
• Patients Per Site Per Month: 3.1

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the effects of administering N-Acetylcysteine (NAC) to assist in initial cessation and/or relapse prevention in adult cigarette smokers.

Condition or Disease	Intervention/Treatment	Phase
Nicotine Dependence; Smoking	Drug: N-acetylcysteine (NAC); Other: Placebo	Phase 2

Detailed Description

The aim of this study is to assess the effects of N-acetylcysteine (NAC) on initial cessation and relapse prevention in adult cigarette smokers. Specifically, this study has the following aims: Aim 1) Examine the efficacy of NAC, compared to placebo, in helping smokers achieve three days of continuous abstinence; Aim 2) Among those who maintain initial 3-day abstinence, examine the time to relapse over the 8-week intervention between NAC and placebo groups; Aim 3) Assess 7-day point prevalence abstinence at the 8-week end-of-treatment study visit in order to obtain effect sizes and estimates of variability to power a randomized clinical trial.

Study Design

• Study Type: Interventional
• Actual Enrollment: 114 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Evaluating N-acetylcysteine as a Pharmacotherapy for Tobacco Use Disorder
• Actual Study Start Date: Aug 30, 2016
• Actual Primary Completion Date: Aug 1, 2019
• Actual Study Completion Date: Oct 10, 2019

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Matched placebo will be given to half of the study participants.	Other: Placebo; Matched placebo (2 capsules taken in the morning and evening) will be taken by study participants for eight weeks. All participants will receive brief smoking cessation counseling and support.
Active Comparator: N-Acetylcysteine (NAC) NAC will be given to half of the study participants. The dose of NAC will be 2400 mg per day (1200 mg taken twice per day as two 600 mg capsules)	Drug: N-acetylcysteine (NAC); NAC or matched placebo will be given to study participants for 8 weeks.; Other Names: NAC

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Biochemically-verified Abstinence From Smoking on Days 1-3 of the Protocol. [Days 1-3 of the study protocol]

   Abstinence will be measured through biochemical verification via breath carbon monoxide. Abstinence is defined as a 75% reduction in carbon monoxide values (parts per million) from smoking baseline levels.

Secondary Outcome Measures

1. Days to Relapse to Smoking Among Abstinent Participants [Days 4-56 of the study protocol]

   Relapse to smoking will be measured through carbon monoxide-verified relapse at weekly study visits among those who abstained during the 3-day quit attempt. Relapse (return to smoking) will be defined as carbon monoxide values (in parts per million) that do not meet abstinence criteria (i.e., 75% reduction from baseline smoking levels).

2. Number of Participants With 7-day Point Prevalence Abstinence at the 8-week End-of-treatment Visit [Days 49-56]

   Seven day point prevalence abstinence will be measured through biochemical verification via breath carbon monoxide and urinary cotinine analysis. Abstinence is defined as a 75% reduction in carbon monoxide values (parts per million) from smoking baseline levels and a negative urine cotinine measure (<80 ng/mL).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Age 18-65

2. Daily smoker for ≥6 months, smoking approximately ≥5 cigarettes per day on average in the past month or must meet the criteria for nicotine dependence

3. Be interested in quitting smoking (defined as a 2 or above on a 10-point Likert scale assessing readiness and interest in quitting (1=not at all ready/interested, 10=extremely ready/interested)

4. Willing to engage in a 3-day quit attempt as part of study procedures

5. Willing to abstain from cannabis use during study procedures (since inhaled cannabis will affect breath carbon monoxide readings).

6. If female, agreement to use birth control (any form) to avoid pregnancy during study procedures

Exclusion Criteria:

1. Any serious or unstable medical/psychiatric disorder (including severe substance use disorders, other than tobacco use disorder) in the past month that may interfere with study performance based on PI judgment

2. Current pregnancy or breastfeeding

3. Current use of medications with smoking cessation efficacy

4. Known hypersensitivity to NAC

5. Use of carbamazepine or nitroglycerin (or any other medication deemed to be hazardous if taken with NAC) within 14 days of study participation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical University of South Carolina	Charleston	South Carolina	United States	29425

Sponsors and Collaborators

• Medical University of South Carolina
• National Institute on Drug Abuse (NIDA)

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 5, 2019

More Information

Publications

None provided.

• Responsible Party: Erin McClure, Assistant Professor, Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT02737358
• Other Study ID Numbers: Pro 00052793; R34DA042228
• First Posted: Apr 13, 2016
• Last Update Posted: Aug 17, 2020
• Last Verified: Jul 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Erin McClure, Assistant Professor, Medical University of South Carolina: nicotine; tobacco; smoking; cessation; N-acetylcysteine; NAC; pharmacotherapy; relapse; tobacco use disorder
• Additional relevant MeSH terms: Tobacco Use Disorder; Acetylcysteine; N-monoacetylcystine

Study Results

Participant Flow

Recruitment Details	Adult daily cigarette smokers were recruited from the community in Charleston, South Carolina (US).
Pre-assignment Detail	Following screening, participants completed mobile daily diaries leading up to a Training visit. During this visit, participants were instructed on how to leave a carbon monoxide samples, upload videos, and loaned equipment to complete remote samples. Prior to randomization, 22 participants withdrew, were lost to follow-up or were discontinued.

Arm/Group Title	Placebo	N-Acetylcysteine (NAC)
Arm/Group Description	Matched placebo will be given to half of the study participants. Placebo: Matched placebo (2 capsules taken in the morning and evening) will be taken by study participants for eight weeks. All participants will receive brief smoking cessation counseling and support.	NAC will be given to half of the study participants. The dose of NAC will be 2400 mg per day (1200 mg taken twice per day as two 600 mg capsules) N-acetylcysteine (NAC): NAC or matched placebo will be given to study participants for 8 weeks.
Period Title: Overall Study
STARTED	55	59
COMPLETED	46	44
NOT COMPLETED	9	15

Baseline Characteristics

Arm/Group Title	Placebo	N-Acetylcysteine (NAC)	Total
Arm/Group Description	Matched placebo will be given to half of the study participants. Placebo: Matched placebo (2 capsules taken in the morning and evening) will be taken by study participants for eight weeks. All participants will receive brief smoking cessation counseling and support.	NAC will be given to half of the study participants. The dose of NAC will be 2400 mg per day (1200 mg taken twice per day as two 600 mg capsules) N-acetylcysteine (NAC): NAC or matched placebo will be given to study participants for 8 weeks.	Total of all reporting groups
Overall Participants	55	59	114
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	55 100%	59 100%	114 100%
>=65 years	0 0%	0 0%	0 0%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	43.9 (11.4)	40.2 (12.2)	42.0 (11.9)
Sex: Female, Male (Count of Participants)
Female	28 50.9%	30 50.8%	58 50.9%
Male	27 49.1%	29 49.2%	56 49.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 10.9%	2 3.4%	8 7%
Not Hispanic or Latino	49 89.1%	57 96.6%	106 93%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 1.7%	1 0.9%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	12 21.8%	21 35.6%	33 28.9%
White	38 69.1%	36 61%	74 64.9%
More than one race	3 5.5%	1 1.7%	4 3.5%
Unknown or Not Reported	2 3.6%	0 0%	2 1.8%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Biochemically-verified Abstinence From Smoking on Days 1-3 of the Protocol.
Description	Abstinence will be measured through biochemical verification via breath carbon monoxide. Abstinence is defined as a 75% reduction in carbon monoxide values (parts per million) from smoking baseline levels.
Time Frame	Days 1-3 of the study protocol

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	N-Acetylcysteine (NAC)
Arm/Group Description	Matched placebo will be given to half of the study participants. Placebo: Matched placebo (2 capsules taken in the morning and evening) will be taken by study participants for eight weeks. All participants will receive brief smoking cessation counseling and support.	NAC will be given to half of the study participants. The dose of NAC will be 2400 mg per day (1200 mg taken twice per day as two 600 mg capsules) N-acetylcysteine (NAC): NAC or matched placebo will be given to study participants for 8 weeks.
Measure Participants	55	59
Count of Participants [Participants]	8 14.5%	6 10.2%

2. Secondary Outcome

Title	Days to Relapse to Smoking Among Abstinent Participants
Description	Relapse to smoking will be measured through carbon monoxide-verified relapse at weekly study visits among those who abstained during the 3-day quit attempt. Relapse (return to smoking) will be defined as carbon monoxide values (in parts per million) that do not meet abstinence criteria (i.e., 75% reduction from baseline smoking levels).
Time Frame	Days 4-56 of the study protocol

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	N-Acetylcysteine (NAC)
Arm/Group Description	Matched placebo will be given to half of the study participants. Placebo: Matched placebo (2 capsules taken in the morning and evening) will be taken by study participants for eight weeks. All participants will receive brief smoking cessation counseling and support.	NAC will be given to half of the study participants. The dose of NAC will be 2400 mg per day (1200 mg taken twice per day as two 600 mg capsules) N-acetylcysteine (NAC): NAC or matched placebo will be given to study participants for 8 weeks.
Measure Participants	55	59
Mean (Standard Error) [days]	17.0 (3.45)	3.8 (1.35)

3. Secondary Outcome

Title	Number of Participants With 7-day Point Prevalence Abstinence at the 8-week End-of-treatment Visit
Description	Seven day point prevalence abstinence will be measured through biochemical verification via breath carbon monoxide and urinary cotinine analysis. Abstinence is defined as a 75% reduction in carbon monoxide values (parts per million) from smoking baseline levels and a negative urine cotinine measure (<80 ng/mL).
Time Frame	Days 49-56

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	N-Acetylcysteine (NAC)
Arm/Group Description	Matched placebo will be given to half of the study participants. Placebo: Matched placebo (2 capsules taken in the morning and evening) will be taken by study participants for eight weeks. All participants will receive brief smoking cessation counseling and support.	NAC will be given to half of the study participants. The dose of NAC will be 2400 mg per day (1200 mg taken twice per day as two 600 mg capsules) N-acetylcysteine (NAC): NAC or matched placebo will be given to study participants for 8 weeks.
Measure Participants	46	44
Count of Participants [Participants]	6 10.9%	4 6.8%

Adverse Events

Time Frame	3 months (randomization to last post-treatment follow-up visit)
Adverse Event Reporting Description	Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Arm/Group Title	Placebo		N-Acetylcysteine (NAC)
Arm/Group Description	Matched placebo will be given to half of the study participants. Placebo: Matched placebo (2 capsules taken in the morning and evening) will be taken by study participants for eight weeks. All participants will receive brief smoking cessation counseling and support.		NAC will be given to half of the study participants. The dose of NAC will be 2400 mg per day (1200 mg taken twice per day as two 600 mg capsules) N-acetylcysteine (NAC): NAC or matched placebo will be given to study participants for 8 weeks.
All Cause Mortality
	Placebo		N-Acetylcysteine (NAC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/55 (0%)		0/59 (0%)
Serious Adverse Events
	Placebo		N-Acetylcysteine (NAC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/55 (0%)		0/59 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		N-Acetylcysteine (NAC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/55 (58.2%)		33/59 (55.9%)
Cardiac disorders
Cardiac Flutter	0/55 (0%)	0	1/59 (1.7%)	1
Tachycarida	0/55 (0%)	0	1/59 (1.7%)	1
Endocrine disorders
Hyperglycemia	1/55 (1.8%)	1	0/59 (0%)	0
Gastrointestinal disorders
Diarrhea	4/55 (7.3%)	4	3/59 (5.1%)	4
Dyspepsia	2/55 (3.6%)	2	2/59 (3.4%)	2
Dry Mouth	0/55 (0%)	0	1/59 (1.7%)	1
Gastroenteritis	0/55 (0%)	0	1/59 (1.7%)	1
Constipation	1/55 (1.8%)	1	0/59 (0%)	0
Malposition Teeth	0/55 (0%)	0	1/59 (1.7%)	1
Nausea	2/55 (3.6%)	2	5/59 (8.5%)	5
Pancreatitis	1/55 (1.8%)	1	0/59 (0%)	0
Peri-umbilical Abdominal Pain	1/55 (1.8%)	1	0/59 (0%)	0
Stomachache	3/55 (5.5%)	3	3/59 (5.1%)	3
Vomiting	2/55 (3.6%)	2	0/59 (0%)	0
Infections and infestations
Bronchitis	3/55 (5.5%)	3	1/59 (1.7%)	1
Cellulitis	1/55 (1.8%)	1	0/59 (0%)	0
Influenza	2/55 (3.6%)	2	1/59 (1.7%)	1
Influenza Like Illness	3/55 (5.5%)	3	2/59 (3.4%)	2
Oral Herpes	1/55 (1.8%)	2	0/59 (0%)	0
Pharyngitis	1/55 (1.8%)	1	0/59 (0%)	0
Sinusitis	2/55 (3.6%)	2	1/59 (1.7%)	1
Tooth Abscess	0/55 (0%)	0	1/59 (1.7%)	1
Urinary Tract Infection	0/55 (0%)	0	2/59 (3.4%)	2
Viral Upper Respiratory Tract Infection	12/55 (21.8%)	12	8/59 (13.6%)	8
Injury, poisoning and procedural complications
Animal Bite	1/55 (1.8%)	1	0/59 (0%)	0
Fracture	1/55 (1.8%)	1	0/59 (0%)	0
Laceration	0/55 (0%)	0	1/59 (1.7%)	1
Post Operative Pain	1/55 (1.8%)	1	1/59 (1.7%)	1
Post Traumatic Pain	0/55 (0%)	0	1/59 (1.7%)	1
Sprained Knee	1/55 (1.8%)	1	0/59 (0%)	0
Musculoskeletal and connective tissue disorders
Hip Pain	1/55 (1.8%)	1	0/59 (0%)	0
Back Pain	1/55 (1.8%)	1	1/59 (1.7%)	1
Back Pain (Worsening)	0/55 (0%)	0	1/59 (1.7%)	1
Intervertebral Disc Protrusion	0/55 (0%)	0	1/59 (1.7%)	1
Neck Pain	0/55 (0%)	0	2/59 (3.4%)	2
Pain in Extremity	2/55 (3.6%)	2	0/59 (0%)	0
Pain in Jaw	0/55 (0%)	0	1/59 (1.7%)	1
Shoulder Pain	0/55 (0%)	0	1/59 (1.7%)	1
Nervous system disorders
Dizziness	1/55 (1.8%)	1	1/59 (1.7%)	1
Headache	1/55 (1.8%)	1	3/59 (5.1%)	3
Migraine	0/55 (0%)	0	2/59 (3.4%)	2
Psychiatric disorders
Depressed Mood	0/55 (0%)	0	3/59 (5.1%)	3
Insomnia	0/55 (0%)	0	1/59 (1.7%)	1
Irritability	1/55 (1.8%)	1	0/59 (0%)	0
Mood Swings	0/55 (0%)	0	1/59 (1.7%)	1
Vivid Dreams	0/55 (0%)	0	1/59 (1.7%)	1
Renal and urinary disorders
Chromaturia	1/55 (1.8%)	1	2/59 (3.4%)	2
Respiratory, thoracic and mediastinal disorders
Cough	1/55 (1.8%)	1	1/59 (1.7%)	1
Dyspnea	0/55 (0%)	0	1/59 (1.7%)	1
Nasal Congestion	1/55 (1.8%)	1	0/59 (0%)	0
Sore Throat	0/55 (0%)	0	1/59 (1.7%)	1
Skin and subcutaneous tissue disorders
Folliculitis	0/55 (0%)	0	1/59 (1.7%)	1
Dermatitis Rash	1/55 (1.8%)	1	0/59 (0%)	0
Pruritus	1/55 (1.8%)	1	0/59 (0%)	0
Skin Abrasion	0/55 (0%)	0	1/59 (1.7%)	1
Vascular disorders
Hypertension (worsening)	2/55 (3.6%)	2	1/59 (1.7%)	1

Limitations/Caveats

[Not Specified]

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.