This trial is active, not recruiting.

Conditions gambling, tobacco use disorder
Treatments n acetyl cysteine, sugar pill
Phase phase 2
Sponsor Yale University
Collaborator National Institute on Drug Abuse (NIDA)
Start date September 2009
End date September 2012
Trial size 80 participants
Trial identifier NCT00967005, 0908M70981, 1RC1DA028279-01


The objective of this application is to examine whether, given its mechanism of action, the dietary supplement, N-acetyl cysteine (NAC) will reduce both tobacco use and pathological gamblers (PG) symptoms in nicotine dependent pathological gamblers.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
The objective of this application is to examine whether, given its mechanism of action, the dietary supplement, N-acetyl cysteine (NAC) will reduce both tobacco use and PG symptoms in nicotine dependent pathological gamblers.
n acetyl cysteine N-acetylcysteine, Acetylcysteine, NAC
N-Acetyl Cysteine, 1200mg-3000mg each day for 24-weeks
(Placebo Comparator)
sugar pill
placebo control

Primary Outcomes

The primary outcome will be at least 4 weeks of continuous abstinence from tobacco at the end of the 12-week treatment period. This will be confirmed by cotinine <10 ng/ml and CO <8 ppm.
time frame: 12 weeks

Secondary Outcomes

Consistent with recent consensus on the assessment of PG severity, the main outcome measures will be money lost gambling per month. This will be assessed using the Gambling Timeline Followback (G-TLFB).
time frame: 24 weeks

Eligibility Criteria

Male or female participants from 18 years up to 75 years old.

Inclusion Criteria: 1. Male and female outpatients, age 18-75 years; 2. Presence of current DSM-IV nicotine dependence and PG for at least 6 months duration; 3. Stable psychotropic drug dose for a period of at least 3 months prior to study entry; 4. Completion of complete blood count, urinalysis, liver function tests, thyroid function tests, and pregnancy test with no evidence of significant lab abnormalities; 5. Signed informed consent Exclusion Criteria: 1. Subjects who are currently receiving individual or group therapy specifically for nicotine dependence or PG symptoms; 2. Currently receiving pharmacotherapies for either nicotine dependence or pathological gambling; 3. Subjects who have started attending Gamblers Anonymous within the 3 months prior to study initiation; 4. Subjects who have an unstable and significant medical illness; 5. Current clinically significant suicidality (score or 3 or 4 on item 3 of the Hamilton Depression Rating Scale) or any other disorder requiring immediate intervention; 6. Lifetime history of bipolar disorder type I or II, dementia, or psychotic disorder; 7. Current (past 12 months) DSM-IV substance abuse or dependence (except nicotine dependence); 8. Borderline or antisocial personality disorder based on the SCID-II; 9. Positive urine drug screen at screening; 10. Asthma (given possible worsening of asthma due to NAC); 11. Cognitive impairment that interferes with the capacity to understand and self-administer medication or provide written informed consent; 12. Current pregnancy or lactation, or inadequate contraception in women of childbearing potential; and 13. Previous treatment with NAC

Additional Information

Official title N-Acetyl Cysteine Plus Behavioral Therapy for Nicotine Dependent Pathological Gamblers
Principal investigator Marc N Potenza, MD, PhD
Description Among US adults, 12.8% report nicotine dependence, and nicotine dependence is highly associated with a variety of DSM-IV Axis I and II disorders (Grant BF et al., 2004). Pathological gambling (PG), a serious public health problem with detrimental effects on individuals and families, and with an estimated yearly cost to society of 5 billion dollars due to lost jobs, debt, bankruptcy, and incarcerations, is associated with elevated proportions of nicotine dependence (41% - 55%), and tobacco smoking in clinical samples of pathological gamblers has been associated with increased gambling severity and more frequent psychiatric problems (Smart & Ferris, 1996; Crockfod & El-Guebaly, 1998; Shaffer et al., 1999; Petry & Oncken, 2002; Potenza et al., 2004; Grant et al., 2005; Falk et al., 2006; Fagan et al., 2007). In addition, research suggests that continued nicotine use is associated with greater rates of relapse among pathological gamblers who received behavioral therapy. Despite increased awareness of the relationship between nicotine dependence and PG, and the possible effects of nicotine dependence on gambling severity, no previous research has focused on how assessment and treatment of nicotine dependence may aid in the successful treatment of PG or smoking cessation. Preliminary research suggests that behavioral therapy using imaginal desensitization and motivational interviewing (IDMI) has shown promise in reducing the symptoms of PG (Grant et al., in press). Despite the efficacy of treatments for PG and nicotine dependence, relapse is common among individuals with nicotine dependence and PG. Preclinical studies have suggested that levels of glutamate within the nucleus accumbens mediate reward-seeking behavior and may underlie relapse seen in addictions. N-acetyl cysteine, a dietary supplement, amino acid and cysteine pro-drug, appears to modulate glutamate within the nucleus accumbens and has shown benefit in reducing the reward-seeking behavior in individuals with cocaine dependence and in pathological gamblers (Baker et al., 2003; LaRowe et al., 2006; Grant et al., 2006). If successful in treating nicotine dependent pathological gamblers, N-acetyl cysteine may serve as a viable, low-cost, and easily available treatment option for nicotine dependent pathological gamblers who receive behavioral therapy. We therefore propose to examine how a dietary supplement, N-acetyl cysteine, used in combination with behavioral therapy, will affect both the urge to smoke and gamble in nicotine dependent pathological gamblers and smoking and gambling behaviors. We therefore propose a randomized placebo-controlled trial of N-acetyl cysteine or placebo with 80 nicotine dependent pathological gamblers who will all receive brief standardized smoking cessation treatment (Ask, Advise, and Refer model) for nicotine cessation and 6 sessions of IDMI for PG. We hypothesize that N-acetyl cysteine plus behavioral therapy will result in greater reduction in both nicotine dependence and PG symptoms during the acute treatment phase and will enhance greater long-term abstinence. Our research will contribute to an improved understanding of the treatment of nicotine-dependent pathological gamblers as well as a greater understanding of the treatment of co-occurring addictions. If our intervention is successful, it will have the potential to set a new standard of care for a range of psychiatric disorders that co-occur with nicotine dependence.
Trial information was received from ClinicalTrials.gov and was last updated in March 2014.
Information provided to ClinicalTrials.gov by Yale University.