Translational Neuropsychopharmacology Research of Nicotine Addiction

Nicotine Dependence, Cigarettes Clinical Trial

Official title:

Translational Neuropsychopharmacology Research of Nicotine Addiction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02723162
• Other study ID #: PRO#48152
• Status: Completed
• Phase: Phase 2
• Start date: May 4, 2016
• Est. completion date: March 9, 2020

Study information

• Verified date: July 2022
• Source: Medical University of South Carolina
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 67
• Est. completion date: March 9, 2020
• Est. primary completion date: March 9, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Nicotine Dependence, Cigarettes
• Tobacco Use Disorder

Intervention

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.
• N-Acetylcysteine (NAC)
NAC will be dosed at 1200 mg twice daily throughout the 28-day active treatment
• Placebo
Matched placebo

Locations

Country	Name	City	State
United States	Medical University of South Carolina	Charleston	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of South Carolina

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change in Blood Oxygen Level Dependent (BOLD) Signal Response	Measure the Effects of Varenicline and N-Acetylcysteine (NAC) on brain activation to smoking images while participants undergo Functional Magnetic Resonance (fMRI) Imaging. Mean percent signal change of fMRI BOLD in the insula and nucleus accumbens will be recorded during smoking images. The lower the BOLD signal response, the better the outcome, meaning reduced reactivity to smoking images.	10 Days
Primary	rZ Change Score in Resting State Functional Connectivity From Baseline	Measure the effects of Varenicline and N-Acetylcysteine on resting-state functional connectivity while participants undergo fMRI. Fisher transformed correlation (rZ) scores will be recorded between medial prefrontal cortex and ventral striatum during a resting state scan. The higher the rZ score, the better the outcome, meaning stronger functional connectivity. rZ scores range from -1 to 1. The rZ-score central value is analogous to a central value to of a Z-score of 0, representing the population mean.	Baseline to day 10
Secondary	Number of Cigarettes Smoked Per Day	Measure the effects of Varenicline and N-Acetylcysteine on smoking behavior over the course of the study	28 Days