Translational Neuropsychopharmacology Research of Nicotine Addiction

NCT ID: NCT02723162

Last Updated: 2022-08-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 67 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-04
• Study Completion Date: 2020-03-09

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.

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.

Conditions

Nicotine Dependence, Cigarettes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: QUADRUPLE

Study Groups

VRN+ NAC

Titrated VRN up to 1mg BID with NAC at 1200mg BID for 28 days

Group Type: EXPERIMENTAL

Varenicline (VRN)

Intervention Type: DRUG

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)

Intervention Type: DRUG

NAC will be dosed at 1200 mg twice daily throughout the 28-day active treatment

NAC+ PBO

1200mg BID for 28 days plus VRN placebo for 28 days

Group Type: ACTIVE_COMPARATOR

N-Acetylcysteine (NAC)

Intervention Type: DRUG

NAC will be dosed at 1200 mg twice daily throughout the 28-day active treatment

Placebo

Intervention Type: DRUG

Matched placebo

VRN+ PBO

Titrated VRN up to 1mg BID with NAC placebo for 28 days

Group Type: ACTIVE_COMPARATOR

Varenicline (VRN)

Intervention Type: DRUG

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.

Placebo

Intervention Type: DRUG

Matched placebo

PBO+PBO

Double placebo taken for 28 days

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matched placebo

Interventions

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.

Intervention Type: DRUG

N-Acetylcysteine (NAC)

NAC will be dosed at 1200 mg twice daily throughout the 28-day active treatment

Intervention Type: DRUG

Placebo

Matched placebo

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Medical University of South Carolina

OTHER

Sponsor Role: lead

Responsible Party

Kevin Gray, MD

Pricipal Investigator - Medical

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Medical University of South Carolina

Charleston, South Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

PRO#48152

Identifier Type: -

Identifier Source: org_study_id