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N-Acetylcysteine for Smoking Cessation in Tobacco and Cannabis Co-Use (NAC_CUD-TUD)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04627922
Recruitment Status : Not yet recruiting
First Posted : November 13, 2020
Last Update Posted : November 13, 2020
Sponsor:
Collaborator:
Tobacco Related Disease Research Program
Information provided by (Responsible Party):
Ellen Herbst, University of California, San Francisco

Brief Summary:
Tobacco and cannabis co-use is a common and growing public health problem, especially in states that have legalized cannabis. There are no pharmacologic treatments for co-occurring tobacco and cannabis use. Co-use may make quitting either substance more difficult, given the synergistic effects of cannabis and nicotine on neurobiological systems that mediate reward and shared cues reinforcing co-use. N-acetylcysteine (NAC), an FDA-approved medication and over-the-counter supplement, has shown promise in animal studies and randomized controlled trials (RCTs) in reducing tobacco and cannabis craving and use.

Condition or disease Intervention/treatment Phase
Cannabis Use Tobacco Use Disorder Drug Use Disorder Drug: N-Acetyl cysteine Other: Placebo comparator Behavioral: Cognitive behavioral therapy (CBT) Phase 4

Detailed Description:
N-acetylcysteine (NAC), an FDA-approved medication and over-the-counter supplement, has shown promise in animal studies and randomized controlled trials (RCTs) in reducing tobacco and cannabis craving and use. NAC's efficacy in treating addiction may be attributable to its central nervous system effects in reducing excessive glutamatergic activity, oxidative stress, and inflammation. NAC has been shown to improve cognition and reduce impulsivity, which in turn may strengthen inhibitory control when presented with contextual cues. To date, no RCT has examined NAC for smoking cessation in the setting of tobacco-cannabis co-use. In a double-blind, placebo-controlled RCT, the investigators will examine a novel pharmacological treatment, NAC, for concurrent tobacco use disorder (TUD) and cannabis use disorder (CUD) in dual users of tobacco and cannabis. Sixty adult daily cigarette smokers who 1) use cannabis regularly and 2) consent to receive interventions to stop smoking cigarettes and using cannabis will be randomized to receive NAC 3600 mg per day or placebo over 8 weeks. Participants in both groups will receive 8 weekly cognitive behavioral therapy sessions addressing both tobacco and cannabis use. Outcomes will be assessed at Weeks 0, 4, 8, and 12. Primary aims are to determine NAC's efficacy in decreasing cigarette use, nicotine dependence levels, and craving; and cannabis use, CUD severity levels, and craving. Exploratory aims include examination of changes in neurocognition with NAC and their potential mediational effects on cigarette and cannabis use outcomes.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description: Double-blind masking
Primary Purpose: Treatment
Official Title: N-Acetylcysteine for Smoking Cessation in Tobacco and Cannabis Co-Use: A Randomized Controlled Trial
Estimated Study Start Date : December 1, 2020
Estimated Primary Completion Date : April 30, 2023
Estimated Study Completion Date : April 30, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: N-acetyl cysteine (NAC) & cognitive behavioral therapy
N-acetyl cysteine (NAC) & cognitive behavioral therapy experimental arm consists of 30 daily cigarette smokers with current TUD and CUD, who will be randomized to receive N-acetyl cysteine 3600 mg per day over 8 weeks to experimental arm. Participants will also receive weekly cognitive behavioral therapy for substance use disorders targeting TUD and CUD.
Drug: N-Acetyl cysteine
The investigators will examine N-acetyl cysteine to treat concurrent tobacco use disorder and cannabis use disorder in a double-blind, placebo-controlled RCT. Sixty daily cigarette smokers with current tobacco use disorder and cannabis use disorder will be randomized to receive NAC 3600 mg per day over 8 weeks.
Other Name: NAC

Behavioral: Cognitive behavioral therapy (CBT)
Participants in both groups will receive 8 weekly cognitive behavioral therapy sessions for substance use disorder targeting both tobacco and cannabis use.
Other Name: CBT

Placebo Comparator: Placebo Comparator: Placebo & cognitive behavioral therapy
Placebo comparator & cognitive behavioral therapy arm consists of 30 daily cigarette smokers with current TUD and CUD, who will be randomized to receive placebo over 8 weeks. Participants will also receive weekly cognitive behavioral therapy for substance use disorders targeting TUD and CUD.
Other: Placebo comparator
The investigators will examine N-acetyl cysteine to treat concurrent tobacco use disorder and cannabis use disorder in a double-blind, placebo-controlled RCT. Sixty daily cigarette smokers with current tobacco use disorder and cannabis use disorder will be randomized to receive placebo per day over 8 weeks.

Behavioral: Cognitive behavioral therapy (CBT)
Participants in both groups will receive 8 weekly cognitive behavioral therapy sessions for substance use disorder targeting both tobacco and cannabis use.
Other Name: CBT




Primary Outcome Measures :
  1. Number of participants with reported drug usage [ Time Frame: Baseline ]
    Participants will participate in urine drug testing which may screen for multiple substances, including amphetamines, methamphetamine, benzodiazepines, barbiturates, marijuana, cocaine, opiates, Phencyclidine (PCP), methadone, nicotine, and alcohol throughout the course of the study. An encrypted email will be sent from VA-protected email accounts from study staff to request an encrypted response with an attached photo image of results. There will be clear instructions to encrypt a de-identified image results message, and the collection of identifying information will not be allowed.

  2. Number of participants with reported drug usage [ Time Frame: 4 weeks ]
    Participants will participate in urine drug testing which may screen for multiple substances, including amphetamines, methamphetamine, benzodiazepines, barbiturates, marijuana, cocaine, opiates, Phencyclidine (PCP), methadone, nicotine, and alcohol throughout the course of the study. An encrypted email will be sent from VA-protected email accounts from study staff to request an encrypted response with an attached photo image of results. There will be clear instructions to encrypt a de-identified image results message, and the collection of identifying information will not be allowed.

  3. Number of participants with reported drug usage [ Time Frame: 8 weeks ]
    Participants will participate in urine drug testing which may screen for multiple substances, including amphetamines, methamphetamine, benzodiazepines, barbiturates, marijuana, cocaine, opiates, Phencyclidine (PCP), methadone, nicotine, and alcohol throughout the course of the study. An encrypted email will be sent from VA-protected email accounts from study staff to request an encrypted response with an attached photo image of results. There will be clear instructions to encrypt a de-identified image results message, and the collection of identifying information will not be allowed.

  4. Number of participants with reported drug usage [ Time Frame: 12 weeks ]
    Participants will participate in urine drug testing which may screen for multiple substances, including amphetamines, methamphetamine, benzodiazepines, barbiturates, marijuana, cocaine, opiates, Phencyclidine (PCP), methadone, nicotine, and alcohol throughout the course of the study. An encrypted email will be sent from VA-protected email accounts from study staff to request an encrypted response with an attached photo image of results. There will be clear instructions to encrypt a de-identified image results message, and the collection of identifying information will not be allowed.

  5. Mean Salivary Cotinine Levels [ Time Frame: 4 weeks ]
    For participants who report not smoking, a saliva sample will be collected to determine salivary cotinine levels at each visit. Cotinine levels are an established method to biochemically verify a participants smoking status.

  6. Mean Salivary Cotinine Levels [ Time Frame: 8 weeks ]
    For participants who report not smoking, a saliva sample will be collected to determine salivary cotinine levels at each visit. Cotinine levels are an established method to biochemically verify a participants smoking status.

  7. Mean Salivary Cotinine Levels [ Time Frame: 12 weeks ]
    For participants who report not smoking, a saliva sample will be collected to determine salivary cotinine levels at each visit. Cotinine levels are an established method to biochemically verify a participants smoking status.

  8. Change in Percentage of Participants with Point Prevalent Abstinence [ Time Frame: Up to 12 weeks ]
    Seven-day point prevalence cigarette abstinence will be defined as the percentage of participants who have reported no smoking or nicotine use on the 7 consecutive days prior to the assessment with biochemically verified cotinine levels of < 10 nanograms/ milliliter.

  9. Changes in Score on the Contemplation Ladder [ Time Frame: Up to 12 weeks ]
    The Contemplation Ladder is a visual analog comprised of 11 rungs and 5 anchor statements, representing stages of change. The response options (0) to (3) corresponded with the stage of precontemplation, (4) to (6) represented the stage of contemplation, (7) and (8) referred to the stage of preparation, (9) and (10) represented the stage of action and stage of maintenance respectively. It is a brief measure of motivation or readiness to change, where (0) is the least motivated and (10) is the most motivated. This measure has been validated for cigarette and other substance use. This measure will be administered twice at each time point both before and after an activity to assess motivation to stop 1) cigarettes and 2) cannabis.

  10. Change in Scores on the Fagerstrom Test for Nicotine Dependence (FTND) [ Time Frame: Up to 12 weeks ]
    The Fagerström Test for Nicotine Dependence is a standard instrument for assessing the intensity of physical addiction to nicotine. It contains six items that evaluate the quantity of cigarette consumption, the compulsion to use, and dependence. In scoring the Fagerstrom Test for Nicotine Dependence, yes/no items are scored from 0 to 1 and multiple-choice items are scored from 0 to 3. The items are summed to yield a total score of 0-10. The higher the total Fagerström score, the more intense is the patient's physical dependence on nicotine.

  11. Change in Scores on the Minnesota Tobacco Withdrawal Scale-Revised (MTWS-R) [ Time Frame: Up to 12 weeks ]
    The MTWS-R features two separate measures for examining the severity of nicotine withdrawal symptoms in a participant: a self-report scale and an observer scale. The observer scale asks the scale-taker to rate the severity of four symptoms in someone the they know who is experiencing nicotine withdrawal: "angry/irritable/frustrated," "anxious/tense," "depressed," and "restless/impatient." The self-report version asks for rankings of the severity of those same four symptoms, plus eleven others that cannot be observed by outsiders (including such things as "desire or craving to smoke," "insomnia, sleep problems, awakening at night," or "dizziness). Both scales use a Likert-type scale for the severity ratings, ranging from 0 ("not at all") to 4 ("severe"). These scores are tallied to calculate an a total withdrawal discomfort score.

  12. Change in Scores on the Questionnaire on Smoking Urges (QSU-Brief): Desire to smoke [ Time Frame: Up to 12 weeks ]
    The QSU-Brief consists of 10 statements about the respondent's feelings and thoughts about his or her desire to smoke cigarettes as he or she is completing the questionnaire (i.e., right now). Each response is scored a number ranging from 1 (strongly disagree) to 7 (strongly agree) and scores are calculated by summing the item scores

  13. Change in Scores on the Questionnaire on Smoking Urges (QSU-Brief): Nicotine withdrawal [ Time Frame: Up to 12 weeks ]
    The QSU-Brief consists of 10 statements about the respondent's feelings and thoughts about his or her desire to smoke cigarettes as he or she is completing the questionnaire (i.e., right now). Each response is scored a number ranging from 1 (strongly disagree) to 7 (strongly agree) and scores are calculated by summing the item scores

  14. Change in Scores on the Questionnaire on Smoking Urges (QSU-Brief): Total [ Time Frame: Up to 12 weeks ]
    The QSU-Brief consists of 10 statements about the respondent's feelings and thoughts about his or her desire to smoke cigarettes as he or she is completing the questionnaire (i.e., right now). Each response is scored a number ranging from 1 (strongly disagree) to 7 (strongly agree) and total scores are calculated by summing the item scores.

  15. Change in Scores on the Cannabis Use Disorder Identification Test - Revised (CUDIT-R) [ Time Frame: Up to 12 weeks ]
    This questionnaire was designed for self-administration and is scored by adding each of the 8 items relating to cannabis use over the past six months. Question 1-7 are scored on a 0-4 scale Question 8 is scored 0,2, or 4. Scores of 8 or more indicate hazardous cannabis use, while scores of 12 or more indicate a possible cannabis use disorder for which further intervention may be required.

  16. Change in Scores on the Marijuana Craving Questionnaire Short Form (MCQ-SF) Total [ Time Frame: Up to 12 weeks ]
    This 12-item multidimensional measure assesses cannabis craving based on 4 factors: Compulsivity, Emotionality, Expectancy, Purposefulness. Each item asks about the respondent's feelings and thoughts about smoking marijuana as he or she is completing the questionnaire (i.e., right now). Each response is scored a number ranging from 1 (strongly disagree) to 7 (strongly agree) and scores are using the mean to the corresponding item. Total Scores are the sum of the means for the 4 subscales.

  17. Change in Scores on the Cannabis Withdrawal Scale [ Time Frame: Up to 12 weeks ]
    This questionnaire is a copyrighted, validated, 19-item assessment of cannabis withdrawal symptoms. Higher total Score is indicative of increasing or decreasing severity of withdrawal

  18. Change in Scores on the Beck Depression Inventory (BDI) [ Time Frame: Up to 12 weeks ]
    The Beck Depression Inventory (BDI) is a 21-item, self-report rating inventory that measures characteristic attitudes and symptoms of depression. Each question had a set of at least four possible responses When the test is scored, a value of 0 to 3 is assigned for each answer and then the total score is compared to a key to determine the depression's severity. The standard cut-off scores were as follows: 0-9 minimal depression, 10-18 indicates mild depression, 19-29 indicates moderate depression, 30-63 indicates severe depression. Higher total scores indicate more severe depressive symptoms.

  19. Change in Scores on the Beck Anxiety Inventory (BAI) [ Time Frame: Up to 12 weeks ]
    The BAI is a 21-item, self-report rating inventory that measures characteristic attitudes and symptoms of anxiety. Each question had a set of at least four possible responses When the test is scored, a value of 0 to 3 is assigned for each answer and then the total score is compared to a key to determine the anxiety severity. The standard cut-off scores were as follows: 0-9 minimal anxiety, 10-18 indicates mild anxiety, 19-29 indicates moderate anxiety, 30-63 indicates severe anxiety. Higher total scores indicate more severe anxiety symptoms.

  20. Change in Scores on the Emotion Regulation Questionnaire (ERQ) [ Time Frame: Up to 12 weeks ]

    The ERQ is a 10-item scale designed to measure respondents' tendency to regulate their emotions in two ways: (1) Cognitive Reappraisal and (2) Expressive Suppression. Respondents answer each item on a 7-point Likert-type scale ranging from 1 (strongly disagree) to 7 (strongly agree). Items 1, 3, 5, 7, 8, 10 make up the Cognitive Reappraisal facet.

    Items 2, 4, 6, 9 make up the Expressive Suppression facet and scores can be summed to create a total score. Higher scores indicate a greater ability for participants to regulate their emotions.


  21. Change in Scores on the Mindful Attention Awareness Scale (MAAS) [ Time Frame: Up to 12 weeks ]
    The MAAS is a 15-item scale measuring dispositional mindfulness by asking respondents' to indicate how frequently they experience mindlessness (i.e., "I run through activities without being really attentive to them") on a 6-point Likert-type scale ranging from 1 (almost always) to 6 (almost never). To score the MAAS, a mean of the 15 items is calculated. Higher scores reflect higher levels of dispositional mindfulness. With these higher scores also come lower reported negative emotional states.

  22. Change in Scores on the Client Satisfaction Questionnaire (CSQ-8) [ Time Frame: Up to 12 weeks ]
    The CSQ-8 is an 8 item measure that will be utilized to measure the satisfaction with the manualized treatment. Items are scored on a Likert scale from 1 (low satisfaction) to 4 (high satisfaction) with different descriptors for each response point. Total scores range from 8 to 32, with higher scores indicating greater satisfaction.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Participants will be male and female daily cigarette smokers ages 18 and over who:

    1. endorse use of smoked cannabis 15 or more of the past 30 days and have positive urine Tetrahydrocannabinol (THC) at Week 0;
    2. meet criteria for Tobacco use disorder (TUD) and Cannabis use disorder (CUD) in the past 12 months per Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), assessed by the Mini International Neuropsychiatric Interview (MINI); and 3) consent to receive interventions to stop smoking cigarettes and using cannabis. Although co-users can use tobacco and cannabis simultaneously (i.e. in "spliffs") and other forms of nicotine and tobacco, participants must smoke combustible cigarettes that are not mixed with cannabis on a daily basis to participate. Female subjects 18-55 must have a negative urine pregnancy test at the time of screening.

Exclusion Criteria:

  1. Psychotic disorders, bipolar disorder, neurocognitive disorder, or other psychiatric or medical conditions judged by the PI to be unstable in the past 30 days, based on MINI.
  2. Concurrent participation in another addiction treatment study or pharmacological study.
  3. Females who are pregnant or lactating.
  4. NAC use at the time of enrollment or at any time during the study period.
  5. Use of medications for TUD (NRT, bupropion, or varenicline) at the time of enrollment or at any time during the study period.
  6. A suicide attempt or suicidal ideation with intent in the 30 days prior to enrollment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04627922


Contacts
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Contact: Joannalyn Delacruz, PhD NACstudy@ncire.org Joannalyn.Delacruz@va.gov
Contact: Nathan Rossi (415)221-4810 ext 23097 Nathan.Rossi@va.gov

Locations
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United States, California
San Francisco VA Medical Center
San Francisco, California, United States, 94121
Contact: REACT LAB    415-221-4810 ext 23097    NACstudy@ncire.org   
Principal Investigator: Ellen Herbst, MD         
Sub-Investigator: Steven Batki, MD         
Sponsors and Collaborators
Ellen Herbst
Tobacco Related Disease Research Program
Investigators
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Principal Investigator: Ellen Herbst, MD SFVA-UCSF
Additional Information:
Publications:
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Responsible Party: Ellen Herbst, Principal Investigator, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT04627922    
Other Study ID Numbers: 20-31475
First Posted: November 13, 2020    Key Record Dates
Last Update Posted: November 13, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ellen Herbst, University of California, San Francisco:
Tobacco
Cannabis
N-acetylcysteine
NAC
Additional relevant MeSH terms:
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Disease
Marijuana Abuse
Tobacco Use Disorder
Substance-Related Disorders
Pathologic Processes
Chemically-Induced Disorders
Mental Disorders
Acetylcysteine
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes