Trial Outcomes & Findings for N-acetylcysteine for Tobacco Use Disorder (NCT NCT02737358)

Last Updated: 2020-08-17

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

114 participants

Primary outcome timeframe

Days 1-3 of the study protocol

Results posted on

2020-08-17

Participant Flow

Adult daily cigarette smokers were recruited from the community in Charleston, South Carolina (US).

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.

Participant milestones

Participant milestones
Measure	Placebo 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.	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) N-acetylcysteine (NAC): NAC or matched placebo will be given to study participants for 8 weeks.
Overall Study STARTED	55	59
Overall Study COMPLETED	46	44
Overall Study NOT COMPLETED	9	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo 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.	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) N-acetylcysteine (NAC): NAC or matched placebo will be given to study participants for 8 weeks.
Overall Study Withdrawal by Subject	7	12
Overall Study Lost to Follow-up	2	3

Baseline Characteristics

N-acetylcysteine for Tobacco Use Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=55 Participants 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.	N-Acetylcysteine (NAC) n=59 Participants 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 n=114 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	55 Participants n=5 Participants	59 Participants n=7 Participants	114 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	43.9 Years STANDARD_DEVIATION 11.4 • n=5 Participants	40.2 Years STANDARD_DEVIATION 12.2 • n=7 Participants	42.0 Years STANDARD_DEVIATION 11.9 • n=5 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	30 Participants n=7 Participants	58 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants	29 Participants n=7 Participants	56 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	49 Participants n=5 Participants	57 Participants n=7 Participants	106 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	12 Participants n=5 Participants	21 Participants n=7 Participants	33 Participants n=5 Participants
Race (NIH/OMB) White	38 Participants n=5 Participants	36 Participants n=7 Participants	74 Participants n=5 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Days 1-3 of the study protocol

Outcome measures

Outcome measures
Measure	Placebo n=55 Participants 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.	N-Acetylcysteine (NAC) n=59 Participants 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.
Number of Participants With Biochemically-verified Abstinence From Smoking on Days 1-3 of the Protocol.	8 Participants	6 Participants

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Placebo n=55 Participants 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.	N-Acetylcysteine (NAC) n=59 Participants 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.
Days to Relapse to Smoking Among Abstinent Participants	17.0 days Standard Error 3.45	3.8 days Standard Error 1.35

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Placebo n=46 Participants 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.	N-Acetylcysteine (NAC) n=44 Participants 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.
Number of Participants With 7-day Point Prevalence Abstinence at the 8-week End-of-treatment Visit	6 Participants	4 Participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 32 other events

Deaths: 0 deaths

N-Acetylcysteine (NAC)

Serious events: 0 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Erin A. McClure, Ph.D.

Medical University of South Carolina

Phone: 843-792-7192

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	Placebo n=55 participants at risk 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.	N-Acetylcysteine (NAC) n=59 participants at risk 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.
Infections and infestations Bronchitis	5.5% 3/55 • Number of events 3 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	1.7% 1/59 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Renal and urinary disorders Chromaturia	1.8% 1/55 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	3.4% 2/59 • Number of events 2 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Respiratory, thoracic and mediastinal disorders Cough	1.8% 1/55 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	1.7% 1/59 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Psychiatric disorders Depressed Mood	0.00% 0/55 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	5.1% 3/59 • Number of events 3 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Gastrointestinal disorders Diarrhea	7.3% 4/55 • Number of events 4 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	5.1% 3/59 • Number of events 4 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Nervous system disorders Dizziness	1.8% 1/55 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	1.7% 1/59 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Gastrointestinal disorders Dyspepsia	3.6% 2/55 • Number of events 2 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	3.4% 2/59 • Number of events 2 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Skin and subcutaneous tissue disorders Folliculitis	0.00% 0/55 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	1.7% 1/59 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Nervous system disorders Headache	1.8% 1/55 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	5.1% 3/59 • Number of events 3 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Musculoskeletal and connective tissue disorders Hip Pain	1.8% 1/55 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	0.00% 0/59 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Endocrine disorders Hyperglycemia	1.8% 1/55 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	0.00% 0/59 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Vascular disorders Hypertension (worsening)	3.6% 2/55 • Number of events 2 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	1.7% 1/59 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Injury, poisoning and procedural complications Animal Bite	1.8% 1/55 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	0.00% 0/59 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Cardiac disorders Cardiac Flutter	0.00% 0/55 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	1.7% 1/59 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Infections and infestations Cellulitis	1.8% 1/55 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	0.00% 0/59 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Musculoskeletal and connective tissue disorders Back Pain	1.8% 1/55 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	1.7% 1/59 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Musculoskeletal and connective tissue disorders Back Pain (Worsening)	0.00% 0/55 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	1.7% 1/59 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Skin and subcutaneous tissue disorders Dermatitis Rash	1.8% 1/55 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	0.00% 0/59 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Gastrointestinal disorders Dry Mouth	0.00% 0/55 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	1.7% 1/59 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/55 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	1.7% 1/59 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Injury, poisoning and procedural complications Fracture	1.8% 1/55 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	0.00% 0/59 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Gastrointestinal disorders Gastroenteritis	0.00% 0/55 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	1.7% 1/59 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Infections and infestations Influenza	3.6% 2/55 • Number of events 2 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	1.7% 1/59 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Infections and infestations Influenza Like Illness	5.5% 3/55 • Number of events 3 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	3.4% 2/59 • Number of events 2 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Gastrointestinal disorders Constipation	1.8% 1/55 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	0.00% 0/59 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Infections and infestations Oral Herpes	1.8% 1/55 • Number of events 2 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	0.00% 0/59 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Psychiatric disorders Insomnia	0.00% 0/55 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	1.7% 1/59 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Musculoskeletal and connective tissue disorders Intervertebral Disc Protrusion	0.00% 0/55 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	1.7% 1/59 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Psychiatric disorders Irritability	1.8% 1/55 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	0.00% 0/59 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Injury, poisoning and procedural complications Laceration	0.00% 0/55 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	1.7% 1/59 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Gastrointestinal disorders Malposition Teeth	0.00% 0/55 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	1.7% 1/59 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Nervous system disorders Migraine	0.00% 0/55 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	3.4% 2/59 • Number of events 2 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Psychiatric disorders Mood Swings	0.00% 0/55 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	1.7% 1/59 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Respiratory, thoracic and mediastinal disorders Nasal Congestion	1.8% 1/55 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	0.00% 0/59 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Gastrointestinal disorders Nausea	3.6% 2/55 • Number of events 2 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	8.5% 5/59 • Number of events 5 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Musculoskeletal and connective tissue disorders Neck Pain	0.00% 0/55 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	3.4% 2/59 • Number of events 2 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Musculoskeletal and connective tissue disorders Pain in Extremity	3.6% 2/55 • Number of events 2 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	0.00% 0/59 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Musculoskeletal and connective tissue disorders Pain in Jaw	0.00% 0/55 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	1.7% 1/59 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Gastrointestinal disorders Pancreatitis	1.8% 1/55 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	0.00% 0/59 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.
Gastrointestinal disorders Peri-umbilical Abdominal Pain	1.8% 1/55 • Number of events 1 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.	0.00% 0/59 • 3 months (randomization to last post-treatment follow-up visit) Assessed and coded in MedDRA terminology by the medical clinician at each visit.