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Translational Neuropsychopharmacology Research of Nicotine Addiction

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ClinicalTrials.gov Identifier: NCT02723162
Recruitment Status : Recruiting
First Posted : March 30, 2016
Last Update Posted : January 31, 2019
Sponsor:
Information provided by (Responsible Party):
Kevin Gray, MD, Medical University of South Carolina

Brief Summary:
This study will examine the effects of combining Varenicline (VRN) and N-acetylcysteine (NAC) on neural circuitry function and treating nicotine addiction. Healthy adult nicotine dependent cigarette smokers interested in quitting (n=110) will be randomized to one of four PBO-controlled conditions for 4 weeks: 1) VRN+NAC, 2) VRN+PBO, 3) NAC+PBO or 4) PBO+PBO. Following 1 week of medication, participants will be contingently reinforced for 3 days of smoking abstinence and be scanned using functional magnetic resonance imaging (fMRI) techniques, while nicotine deprived during a resting state and a cue-reactivity (CR) task. Participants will be followed over the next 3 weeks of treatment and clinical variables will be assessed.

Condition or disease Intervention/treatment Phase
Nicotine Dependence, Cigarettes Drug: Varenicline (VRN) Drug: N-Acetylcysteine (NAC) Drug: Placebo Not Applicable

Detailed Description:
Cigarette (henceforth nicotine) addiction is a chronic, relapsing brain disorder and remains the leading preventable cause of death and disability in the US, costing nearly $200 billion each year. Although ~20% of adults in the USA currently smoke, the majority want to quit. In spite of the breadth of research focused on improving health outcomes and reducing the societal burden caused by nicotine addiction, the majority of smokers who attempt to quit will relapse. Nicotine withdrawal-related disturbances in executive function, negative affect and reward processes compel a smoker to self-administer nicotine—each in turn representing the loss of control to remain abstinent and risk factors for relapse. Thus, identifying the effects of nicotine addiction on mechanisms of self-regulation, and the value of novel medications for remediating dysregulated behavior are both needed in order to enhance interventions for treating nicotine addiction. The preliminary data, along with the extant literature, suggest that the maintenance of nicotine addiction is subserved by dysregulated neural function in limbic-striatal and corticostriatal neural circuitry. While VRN may be effective in treating limbic-striatal circuitry that is associated with promoting abstinence and reducing acute withdrawal; NAC may be effective in treating corticostriatal circuitry function that is associated with relapse vulnerability. Thus, the current proposal seeks to investigate two medications (VRN & NAC), with potentially complementary effects on the two different brain circuits— limbic-striatal (VRN) and corticostriatal (NAC) circuitry—and that may therapeutically target two different phases in the recovery of nicotine addiction—the promotion of abstinence (VRN) and relapse prevention (NAC). The placebo (PBO)-controlled design in this proposal will allow the team to identify and translate between the neurobiological substrates and the neurocognitive underpinnings of the effects of VRN+NAC on smoking behavior in humans—thus, advancing the understanding of the pathophysiology of nicotine addiction.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Health Services Research
Official Title: Translational Neuropsychopharmacology Research of Nicotine Addiction
Study Start Date : January 2016
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : July 2020

Arm Intervention/treatment
Experimental: VRN+ NAC
Titrated VRN up to 1mg BID with NAC at 1200mg BID for 28 days
Drug: Varenicline (VRN)
VRN will be provided at the standard recommended dose (0.5 mg daily for 3 days, then 0.5 mg twice daily for 4 days, then 1 mg twice daily thereafter for the remaining 21 days of active treatment.

Drug: N-Acetylcysteine (NAC)
NAC will be dosed at 1200 mg twice daily throughout the 28-day active treatment

Active Comparator: NAC+ PBO
1200mg BID for 28 days plus VRN placebo for 28 days
Drug: N-Acetylcysteine (NAC)
NAC will be dosed at 1200 mg twice daily throughout the 28-day active treatment

Drug: Placebo
Matched placebo

Active Comparator: VRN+ PBO
Titrated VRN up to 1mg BID with NAC placebo for 28 days
Drug: Varenicline (VRN)
VRN will be provided at the standard recommended dose (0.5 mg daily for 3 days, then 0.5 mg twice daily for 4 days, then 1 mg twice daily thereafter for the remaining 21 days of active treatment.

Drug: Placebo
Matched placebo

Placebo Comparator: PBO+PBO
Double placebo taken for 28 days
Drug: Placebo
Matched placebo




Primary Outcome Measures :
  1. Measure the effects of Varenicline and N-Acetylcysteine on fMRI BOLD response to images while participants undergo functional magnetic resonance imaging [ Time Frame: 10 Days ]
  2. Measure the effects of Varenicline and N-Acetylcysteine on resting-state functional connectivity while participants undergo functional magnetic resonance imaging [ Time Frame: 10 days ]

Secondary Outcome Measures :
  1. Measure the effects of Varenicline and N-Acetylcysteine on smoking behavior over the course of the study [ Time Frame: 28 Days ]
    Number of cigarettes smoked



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Age 18 - 55
  2. Right Handed
  3. English fluency
  4. 20/20 vision with corrective lenses.
  5. Smoke ≥ 10 cigarettes/day for a minimum of two years and have an expired carbon monoxide (CO) concentration of ≥ 10 ppm (to confirm inhalation).
  6. Interest in quitting smoking or contemplating a quit attempt in the next 6 months
  7. If female, agreement to use birth control

Exclusion Criteria:

  1. Past head injury or primary neurological disorder associated with MRI abnormalities, including dementia, MCI, brain tumors, epilepsy, Parkinson's disease, or demyelinating diseases
  2. Any physical or intellectual disability affecting completion of assessments
  3. Any contraindication to MRI
  4. Positive urine drug screen for illicit substances (such as marijuana or cocaine).
  5. Current or past psychosis
  6. Electroconvulsive therapy in last 6 months
  7. Use of antidepressant medications or other psychotropic medications in the last month.
  8. Positive urine pregnancy test or current breast feeding status

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): NCT02723162


Locations
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United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29403
Contact: Lori Ann Ueberroth    843-792-8220    ueberro@musc.edu   
Principal Investigator: Kevin Gray, MD         
Sponsors and Collaborators
Medical University of South Carolina

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Responsible Party: Kevin Gray, MD, Pricipal Investigator - Medical, Medical University of South Carolina
ClinicalTrials.gov Identifier: NCT02723162     History of Changes
Other Study ID Numbers: PRO#48152
First Posted: March 30, 2016    Key Record Dates
Last Update Posted: January 31, 2019
Last Verified: January 2019

Additional relevant MeSH terms:
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Tobacco Use Disorder
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Nicotine
Varenicline
Acetylcysteine
N-monoacetylcystine
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Protective Agents
Antidotes