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N-Acetyl Cysteine Plus Behavioral Therapy for Nicotine Dependent Pathological Gamblers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00967005
Recruitment Status : Completed
First Posted : August 27, 2009
Results First Posted : July 7, 2017
Last Update Posted : July 7, 2017
Sponsor:
Collaborators:
National Institute on Drug Abuse (NIDA)
University of Minnesota
Information provided by (Responsible Party):
Jon Grant, University of Chicago

Tracking Information
First Submitted Date  ICMJE August 25, 2009
First Posted Date  ICMJE August 27, 2009
Results First Submitted Date  ICMJE April 3, 2017
Results First Posted Date  ICMJE July 7, 2017
Last Update Posted Date July 7, 2017
Study Start Date  ICMJE September 2009
Actual Primary Completion Date September 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 29, 2017)
  • Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling Total Score [ Time Frame: Week 0 ]
    Week 0 corresponds to baseline. Minimum score=0 and maximum score=40, with higher score signifying more severe symptoms. Scale is 10 items scored from 0 to 4. Scores on each item are summed to compute total score. Thoughts/urges (questions 1 to 5) and behavior (questions 6 to 10) are added to get the total score.
  • Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling Total Score [ Time Frame: Week 6 ]
    Week 6 corresponds to end of N-acetylcysteine plus Ask-Advise-Refer therapy versus placebo plus Ask-Advise-Refer therapy. Minimum score=0 and maximum score=40, with higher score signifying more severe symptoms. Scale is 10 items scored from 0 to 4. Scores on each item are summed to compute total score. Thoughts/urges (questions 1 to 5) and behavior (questions 6 to 10) are added to get the total score.
  • Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling Total Score [ Time Frame: Week 12 ]
    Week 12 corresponds to end of 6 sessions of N-acetylcysteine plus imaginal desensitization and motivational interviewing versus placebo plus imaginal desensitization and motivational interviewing. Minimum score=0 and maximum score=40, with higher score signifying more severe symptoms. Scale is 10 items scored from 0 to 4. Scores on each item are summed to compute total score. Thoughts/urges (questions 1 to 5) and behavior (questions 6 to 10) are added to get the total score.
  • Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling Total Score [ Time Frame: Week 24 ]
    Week 24 represents the 3-month follow-up period (ie, corresponds to being off N-acetylcysteine or placebo and done with imaginal desensitization and motivational interviewing for 12 weeks). Minimum score=0 and maximum score=40, with higher score signifying more severe symptoms. Scale is 10 items scored from 0 to 4. Scores on each item are summed to compute total score. Thoughts/urges (questions 1 to 5) and behavior (questions 6 to 10) are added to get the total score.
  • Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling Urges/Thoughts Subscale [ Time Frame: Week 0 ]
    Week 0 corresponds to baseline. Questions 1 through 5 are summed to compute the thoughts/urges subscale. Minimum=0 and maximum=20, with higher scores signifying more severe thoughts/urges.
  • Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling Urges/Thoughts Subscale [ Time Frame: Week 6 ]
    Week 6 corresponds to end of N-acetylcysteine plus Ask-Advise-Refer therapy versus placebo plus Ask-Advise-Refer therapy. Questions 1 through 5 are summed to compute the thoughts/urges subscale. Minimum=0 and maximum=20, with higher scores signifying more severe thoughts/urges.
  • Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling Urges/Thoughts Subscale [ Time Frame: Week 12 ]
    Week 12 corresponds to end of 6 sessions of N-acetylcysteine plus imaginal desensitization and motivational interviewing versus placebo plus imaginal desensitization and motivational interviewing. Questions 1 through 5 are summed to compute the thoughts/urges subscale. Minimum=0 and maximum=20, with higher scores signifying more severe thoughts/urges.
  • Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling Urges/Thoughts Subscale [ Time Frame: Week 24 ]
    Week 24 represents the 3-month follow-up period (ie, corresponds to being off N-acetylcysteine or placebo and done with imaginal desensitization and motivational interviewing for 12 weeks). Questions 1 through 5 are summed to compute the thoughts/urges subscale. Minimum=0 and maximum=20, with higher scores signifying more severe thoughts/urges.
  • Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling Behavior Subscale [ Time Frame: Week 0 ]
    Week 0 corresponds to baseline. Questions 6 through 10 are summed to compute the thoughts/urges subscale. Minimum=0 and maximum=20, with higher scores signifying more severe gambling behaviors.
  • Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling Behavior Subscale [ Time Frame: Week 6 ]
    Week 6 corresponds to end of N-acetylcysteine plus Ask-Advise-Refer therapy versus placebo plus Ask-Advise-Refer therapy. . Questions 6 through 10 are summed to compute the thoughts/urges subscale. Minimum=0 and maximum=20, with higher scores signifying more severe gambling behaviors.
  • Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling Behavior Subscale [ Time Frame: Week 12 ]
    Week 12 corresponds to end of 6 sessions of N-acetylcysteine plus imaginal desensitization and motivational interviewing versus placebo plus imaginal desensitization and motivational interviewing. Questions 6 through 10 are summed to compute the thoughts/urges subscale. Minimum=0 and maximum=20, with higher scores signifying more severe gambling behaviors.
  • Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling Behavior Subscale [ Time Frame: Week 24 ]
    Week 24 represents the 3-month follow-up period (ie, corresponds to being off N-acetylcysteine or placebo and done with imaginal desensitization and motivational interviewing for 12 weeks). Questions 6 through 10 are summed to compute the thoughts/urges subscale. Minimum=0 and maximum=20, with higher scores signifying more severe gambling behaviors.
  • Fagerstrom Test for Nicotine Dependence Total Score [ Time Frame: Week 0 ]
    Week 0 corresponds to baseline. This scale has 6 questions. Questions 1 and 4 are on a scale from 0 to 3 (higher scores being more severe symptoms) and questions 2, 3, 5, and 6 are on a scale from 0 to 1 (1 being more severe symptoms). Scores on all questions are summed to compute total score, with higher total score meaning more severe nicotine dependence. Scores range from 0 to 10.
  • Fagerstrom Test for Nicotine Dependence Total Score [ Time Frame: Week 6 ]
    Week 6 corresponds to end of N-acetylcysteine plus Ask-Advise-Refer therapy versus placebo plus Ask-Advise-Refer therapy. This scale has 6 questions. Questions 1 and 4 are on a scale from 0 to 3 (higher scores being more severe symptoms) and questions 2, 3, 5, and 6 are on a scale from 0 to 1 (1 being more severe symptoms). Scores on all questions are summed to compute total score, with higher total score meaning more severe nicotine dependence. Scores range from 0 to 10.
  • Fagerstrom Test for Nicotine Dependence Total Score [ Time Frame: Week 12 ]
    Week 12 corresponds to end of 6 sessions of N-acetylcysteine plus imaginal desensitization and motivational interviewing versus placebo plus imaginal desensitization and motivational interviewing. This scale has 6 questions. Questions 1 and 4 are on a scale from 0 to 3 (higher scores being more severe symptoms) and questions 2, 3, 5, and 6 are on a scale from 0 to 1 (1 being more severe symptoms). Scores on all questions are summed to compute total score, with higher total score meaning more severe nicotine dependence. Scores range from 0 to 10.
  • Fagerstrom Test for Nicotine Dependence Total Score [ Time Frame: Week 24 ]
    Week 24 represents the 3-month follow-up period (ie, corresponds to being off N-acetylcysteine or placebo and done with imaginal desensitization and motivational interviewing for 12 weeks). This scale has 6 questions. Questions 1 and 4 are on a scale from 0 to 3 (higher scores being more severe symptoms) and questions 2, 3, 5, and 6 are on a scale from 0 to 1 (1 being more severe symptoms). Scores on all questions are summed to compute total score, with higher total score meaning more severe nicotine dependence. Scores range from 0 to 10.
  • Hamilton Depression Rating Scale Total Score [ Time Frame: Week 0 ]
    Week 0 corresponds to baseline. This scale assesses depressed mood, feelings of guilt, difficulty sleeping, somatic symptoms, and others. Total score is computed by summing the scores of the 17 items. Minimum score is 0 and maximum score is 52, with higher scores signifying more severe depressive symptoms.
  • Hamilton Depression Rating Scale Total Score [ Time Frame: Week 6 ]
    Week 6 corresponds to end of N-acetylcysteine plus Ask-Advise-Refer therapy versus placebo plus Ask-Advise-Refer therapy. This scale assesses depressed mood, feelings of guilt, difficulty sleeping, somatic symptoms, and others. Total score is computed by summing the scores of the 17 items. Minimum score is 0 and maximum score is 52, with higher scores signifying more severe depressive symptoms.
  • Hamilton Depression Rating Scale Total Score [ Time Frame: Week 12 ]
    Week 12 corresponds to end of 6 sessions of N-acetylcysteine plus imaginal desensitization and motivational interviewing versus placebo plus imaginal desensitization and motivational interviewing. This scale assesses depressed mood, feelings of guilt, difficulty sleeping, somatic symptoms, and others. Total score is computed by summing the scores of the 17 items. Minimum score is 0 and maximum score is 52, with higher scores signifying more severe depressive symptoms.
  • Hamilton Depression Rating Scale Total Score [ Time Frame: Week 24 ]
    Week 24 represents the 3-month follow-up period (ie, corresponds to being off N-acetylcysteine or placebo and done with imaginal desensitization and motivational interviewing for 12 weeks). This scale assesses depressed mood, feelings of guilt, difficulty sleeping, somatic symptoms, and others. Total score is computed by summing the scores of the 17 items. Minimum score is 0 and maximum score is 52, with higher scores signifying more severe depressive symptoms.
  • Hamilton Anxiety Rating Scale Total Score [ Time Frame: Week 0 ]
    Week 0 corresponds to baseline. This scale measures anxiety symptoms, tension, somatic symptoms, difficulty concentrating, and others. Total score is computed by summing the scores on the 14 items (each item is scored from 0 to 4). Minimum score= 0 and maximum score= 56, with higher scores signifying more severe anxiety symptoms.
  • Hamilton Anxiety Rating Scale Total Score [ Time Frame: Week 6 ]
    Week 6 corresponds to end of N-acetylcysteine plus Ask-Advise-Refer therapy versus placebo plus Ask-Advise-Refer therapy. This scale measures anxiety symptoms, tension, somatic symptoms, difficulty concentrating, and others. Total score is computed by summing the scores on the 14 items (each item is scored from 0 to 4). Minimum score= 0 and maximum score= 56, with higher scores signifying more severe anxiety symptoms.
  • Hamilton Anxiety Rating Scale Total Score [ Time Frame: Week 12 ]
    Week 12 corresponds to end of 6 sessions of N-acetylcysteine plus imaginal desensitization and motivational interviewing versus placebo plus imaginal desensitization and motivational interviewing. This scale measures anxiety symptoms, tension, somatic symptoms, difficulty concentrating, and others. Total score is computed by summing the scores on the 14 items (each item is scored from 0 to 4). Minimum score= 0 and maximum score= 56, with higher scores signifying more severe anxiety symptoms.
  • Hamilton Anxiety Rating Scale Total Score [ Time Frame: Week 24 ]
    Week 24 represents the 3-month follow-up period (ie, corresponds to being off N-acetylcysteine or placebo and done with imaginal desensitization and motivational interviewing for 12 weeks). This scale measures anxiety symptoms, tension, somatic symptoms, difficulty concentrating, and others. Total score is computed by summing the scores on the 14 items (each item is scored from 0 to 4). Minimum score= 0 and maximum score= 56, with higher scores signifying more severe anxiety symptoms.
Original Primary Outcome Measures  ICMJE
 (submitted: August 26, 2009)
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 ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: August 26, 2009)
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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE N-Acetyl Cysteine Plus Behavioral Therapy for Nicotine Dependent Pathological Gamblers
Official Title  ICMJE N-Acetyl Cysteine Plus Behavioral Therapy for Nicotine Dependent Pathological Gamblers
Brief Summary 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.
Detailed 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Gambling
  • Tobacco Use Disorder
Intervention  ICMJE
  • Drug: N Acetyl Cysteine
    N-Acetyl Cysteine, 1200mg-3000mg each day for 24-weeks
    Other Name: N-acetylcysteine, Acetylcysteine, NAC
  • Other: Sugar Pill
    placebo control
Study Arms  ICMJE
  • Experimental: N Acetyl Cysteine
    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.
    Intervention: Drug: N Acetyl Cysteine
  • Placebo Comparator: Sugar Pill
    Intervention: Other: Sugar Pill
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 29, 2017)
28
Original Estimated Enrollment  ICMJE
 (submitted: August 26, 2009)
80
Actual Study Completion Date  ICMJE August 2014
Actual Primary Completion Date September 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00967005
Other Study ID Numbers  ICMJE 0908M70981
1RC1DA028279-01 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jon Grant, University of Chicago
Study Sponsor  ICMJE University of Chicago
Collaborators  ICMJE
  • National Institute on Drug Abuse (NIDA)
  • University of Minnesota
Investigators  ICMJE
Principal Investigator: Marc N Potenza, MD, PhD Yale University
Principal Investigator: Jon E Grant, MD, JD, MPH University of Minnesota
PRS Account University of Chicago
Verification Date June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP