NCT01214083

N-acetylcysteine Plus Naltrexone for the Treatment of Alcohol Dependence

Completed Phase 2 Results posted Last updated 8 April 2020

What this trial tests

Phase 2 trial testing N-acetylcysteine + high-dose naltrexone (150 mg) in Alcoholism in 111 participants. Completed in 30 October 2016.

Timeline

15 October 2010

Primary endpoint
30 September 2015

30 October 2016

Quick facts

Lead sponsor	VA Office of Research and Development
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	111
Start date	15 October 2010
Primary completion	30 September 2015
Estimated completion	30 October 2016
Sites	2 locations across United States

Drugs / interventions tested

• N-acetylcysteine + high-dose naltrexone (150 mg) — full drug profile →
• High-dose naltrexone (150 mg) alone — full drug profile →
• Low-dose naltrexone (50 mg) alone — full drug profile →

Conditions studied

• Alcoholism — all drugs for Alcoholism →

Sponsor

VA Office of Research and Development — full company profile →

Who can join

Adults 18 to 65, any sex, with Alcoholism. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Heavy Drinking Days Primary · week 1 and week 13

"Percentage of heavy drinking days" was measured by the Time Line Follow Back (TLFB) Method. ('Heavy drinking' was defined as 5 or more standard drinks per day for men and 4 or more standard drinks for women.) The percentage has a total range of 0%-100%. Higher percentages represent a worse outcome (i.e., more heavy drinking).

Percentage of heavy drinking days at week 1

Group	Value	95% CI
N-acetylcysteine + High-dose Naltrexone (150 mg)	45.0	± 4.5
High-dose Naltrexone (150 mg) Alone	50.6	± 4.3
Low-dose Naltrexone (50 mg) Alone	44.0	± 4.5

Percentage of heavy drinking days at week 13

Group	Value	95% CI
N-acetylcysteine + High-dose Naltrexone (150 mg)	5.2	± 5.6
High-dose Naltrexone (150 mg) Alone	3.4	± 5.1
Low-dose Naltrexone (50 mg) Alone	3.3	± 5.3

Liver Function Tests (AST) Secondary · week 0 and week 13

Liver function tests (AST) at week 0

Group	Value	95% CI
N-acetylcysteine + High-dose Naltrexone (150 mg)	34.7	± 6.6
High-dose Naltrexone (150 mg) Alone	29.0	± 6.4
Low-dose Naltrexone (50 mg) Alone	30.0	± 6.6

Liver function tests (AST) at week 13

Group	Value	95% CI
N-acetylcysteine + High-dose Naltrexone (150 mg)	27.3	± 7.9
High-dose Naltrexone (150 mg) Alone	32.1	± 7.4
Low-dose Naltrexone (50 mg) Alone	22.2	± 7.5

Penn Alcohol Craving Scale (PACS) Secondary · week 1 and week 13

The Penn Alcohol Craving Scale is designed to assess alcohol craving severity. The scale has a total score range of 0-30. Higher values represent a worse outcome (i.e., higher craving).

Penn Alcohol Craving Scale at week 1

Group	Value	95% CI
N-acetylcysteine + High-dose Naltrexone (150 mg)	18.0	± 1.1
High-dose Naltrexone (150 mg) Alone	18.4	± 1.1
Low-dose Naltrexone (50 mg) Alone	16.1	± 1.1

Penn Alcohol Craving Scale at week 13

Group	Value	95% CI
N-acetylcysteine + High-dose Naltrexone (150 mg)	7.2	± 1.4
High-dose Naltrexone (150 mg) Alone	8.3	± 1.3
Low-dose Naltrexone (50 mg) Alone	6.3	± 1.3

Obsessive Compulsive Drinking Scale (OCDS) Secondary · week 1 and week 13

The Obsessive Compulsive Drinking Scale is designed to assess obsessive and compulsive aspects of alcoholism. The scale has a total score range of 0-56. Higher values represent a worse outcome (i.e., more alcohol problems).

Obsessive Compulsive Drinking Scale at week 1

Group	Value	95% CI
N-acetylcysteine + High-dose Naltrexone (150 mg)	28.2	± 1.8
High-dose Naltrexone (150 mg) Alone	29.0	± 1.7
Low-dose Naltrexone (50 mg) Alone	24.5	± 1.8

Obsessive Compulsive Drinking Scale at week 13

Group	Value	95% CI
N-acetylcysteine + High-dose Naltrexone (150 mg)	9.1	± 2.1
High-dose Naltrexone (150 mg) Alone	14.0	± 1.9
Low-dose Naltrexone (50 mg) Alone	9.0	± 2.0

Clinical Global Impression (CGI) Secondary · week 1 and week 13

The Clinical Global Impression is designed to assess overall severity of illness. The scale has a total score range of 1-7. Higher values represent a worse outcome (i.e., severe illness).

Clinical Global Impression at week 1

Group	Value	95% CI
N-acetylcysteine + High-dose Naltrexone (150 mg)	3.7	± 0.1
High-dose Naltrexone (150 mg) Alone	3.7	± 0.1
Low-dose Naltrexone (50 mg) Alone	3.6	± 0.1

Clinical Global Impression at week 13

Group	Value	95% CI
N-acetylcysteine + High-dose Naltrexone (150 mg)	1.5	± 0.2
High-dose Naltrexone (150 mg) Alone	1.7	± 0.2
Low-dose Naltrexone (50 mg) Alone	1.4	± 0.2

Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Secondary · week 1 and week 13

The Quality of Life Enjoyment and Satisfaction Questionnaire is designed to assess a quality of life. The scale has a total score range of 16-80. Higher values represent a better outcome (i.e., better quality of life).

Q-LES-Q at week 1

Group	Value	95% CI
N-acetylcysteine + High-dose Naltrexone (150 mg)	53.2	± 1.9
High-dose Naltrexone (150 mg) Alone	53.8	± 1.8
Low-dose Naltrexone (50 mg) Alone	55.1	± 1.9

Q-LES-Q at week 13

Group	Value	95% CI
N-acetylcysteine + High-dose Naltrexone (150 mg)	61.6	± 2.1
High-dose Naltrexone (150 mg) Alone	59.6	± 2.0
Low-dose Naltrexone (50 mg) Alone	63.9	± 2.1

Percentage of Drinking Days Secondary · week 1 and week 13

"Percentage of drinking days" was measured by the Time Line Follow Back (TLFB) Method. The percentage has a total range of 0%-100%. Higher percentages represent a worse outcome (i.e., more drinking days).

percentage of drinking days at week 1

Group	Value	95% CI
N-acetylcysteine + High-dose Naltrexone (150 mg)	64.6	± 6.3
High-dose Naltrexone (150 mg) Alone	63.8	± 6.1
Low-dose Naltrexone (50 mg) Alone	55.3	± 6.3

percentage of drinking days at week 13

Group	Value	95% CI
N-acetylcysteine + High-dose Naltrexone (150 mg)	21.1	± 7.6
High-dose Naltrexone (150 mg) Alone	24.5	± 7.0
Low-dose Naltrexone (50 mg) Alone	18.2	± 7.3

Drinks Per Drinking Days Secondary · week 1 and week 13

drinks per drinking days at week 1

Group	Value	95% CI
N-acetylcysteine + High-dose Naltrexone (150 mg)	7.3	± 0.6
High-dose Naltrexone (150 mg) Alone	5.9	± 0.6
Low-dose Naltrexone (50 mg) Alone	7.3	± 0.6

drinks per drinking days at week 13

Group	Value	95% CI
N-acetylcysteine + High-dose Naltrexone (150 mg)	1.1	± 0.6
High-dose Naltrexone (150 mg) Alone	1.2	± 0.6
Low-dose Naltrexone (50 mg) Alone	1.0	± 0.6

Liver Function Tests (ALT) Secondary · week 0 and week 13

Liver Function Tests (ALT) at week 0

Group	Value	95% CI
N-acetylcysteine + High-dose Naltrexone (150 mg)	49.4	± 12.0
High-dose Naltrexone (150 mg) Alone	36.5	± 11.6
Low-dose Naltrexone (50 mg) Alone	34.7	± 12.0

Liver Function Tests (ALT) at week 13

Group	Value	95% CI
N-acetylcysteine + High-dose Naltrexone (150 mg)	27.6	± 13.9
High-dose Naltrexone (150 mg) Alone	40.1	± 13.0
Low-dose Naltrexone (50 mg) Alone	31.3	± 13.2

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

N-acetylcysteine + High-dose Naltrexone (150 mg)

Serious: 0/31 (0%)

Deaths: —

High-dose Naltrexone (150 mg) Alone

Serious: 0/33 (0%)

Deaths: —

Low-dose Naltrexone (50 mg) Alone

Serious: 0/31 (0%)

Deaths: —

Other adverse events (6 terms — click to expand)

Reaction	System	N-acetylcysteine + High-do…	High-dose Naltrexone (150 …	Low-dose Naltrexone (50 mg…
Nausea	Gastrointestinal disorders	—	—	—
Drowsiness	General disorders	—	—	—
Headache	General disorders	—	—	—
Decreased appetite	General disorders	—	—	—
Dry mouth	General disorders	—	—	—
Stomach discomfort	Gastrointestinal disorders	—	—	—

Data from ClinicalTrials.gov NCT01214083 adverse events section.

Sponsor's own description

The purpose of this study is to determine whether: (1) the combination of N-acetylcysteine + high-dose naltrexone (150 mg) works better than high-dose naltrexone (150 mg) alone in reducing alcohol drinking; and (2) high-dose naltrexone (150 mg) alone works better than low-dose naltrexone (50 mg) alone in reducing alcohol drinking.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

1. Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects.
   Ru Q, Li Y, Chen L, Wu Y, et al · · 2024 · cited 365× · PMID 39396974 · DOI 10.1038/s41392-024-01969-z
2. Neuroimmune signaling in alcohol use disorder.
   Erickson EK, Grantham EK, Warden AS, Harris RA. · · 2019 · cited 189× · PMID 30590091 · DOI 10.1016/j.pbb.2018.12.007
3. Potential role of N-acetylcysteine in the management of substance use disorders.
   McClure EA, Gipson CD, Malcolm RJ, Kalivas PW, et al · · 2014 · cited 114× · PMID 24442756 · DOI 10.1007/s40263-014-0142-x
4. Alcohol-Induced Oxidative Stress and the Role of Antioxidants in Alcohol Use Disorder: A Systematic Review.
   Tsermpini EE, Plemenitaš Ilješ A, Dolžan V. · · 2022 · cited 98× · PMID 35883865 · DOI 10.3390/antiox11071374
5. Immune treatments for alcohol use disorder: A translational framework.
   Meredith LR, Burnette EM, Grodin EN, Irwin MR, et al · · 2021 · cited 50× · PMID 34343618 · DOI 10.1016/j.bbi.2021.07.023
6. Ferroptosis in Cancer and Inflammatory Diseases: Mechanisms and Therapeutic Implications.
   Shen G, Liu J, Wang Y, Deng Z, et al · · 2025 · cited 6× · PMID 40919133 · DOI 10.1002/mco2.70349