Translational Neuropsychopharmacology Research of Nicotine Addiction

NCT02723162 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: PRO#48152
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

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.

Conditions

Nicotine Dependence, Cigarettes

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (1)

• Number of Cigarettes Smoked Per Day

  28 Days

Study Arms (4)

VRN+ NAC

EXPERIMENTAL

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

Drug: Varenicline (VRN); Drug: N-Acetylcysteine (NAC)

NAC+ PBO

ACTIVE COMPARATOR

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

Drug: N-Acetylcysteine (NAC); Drug: Placebo

VRN+ PBO

ACTIVE COMPARATOR

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

Drug: Varenicline (VRN); Drug: Placebo

PBO+PBO

PLACEBO COMPARATOR

Double placebo taken for 28 days

Drug: Placebo

Interventions

Varenicline (VRN) 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.

VRN+ NAC; VRN+ PBO

N-Acetylcysteine (NAC) DRUG

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

NAC+ PBO; VRN+ NAC

Placebo DRUG

Matched placebo

NAC+ PBO; PBO+PBO; VRN+ PBO

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Medical University of South Carolina: lead

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29403, United States

Location

MeSH Terms

Conditions

Tobacco Use Disorder

Interventions

Varenicline; Acetylcysteine

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinoxalines; Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Limitations and Caveats

The study did not reach full planned enrollment due to COVID-19.

Results Point of Contact

• Title: Dr. Kevin Gray
• Organization: Medical University of South Carolina

graykm@musc.edu

843-792-9162

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pricipal Investigator - Medical

Study Record Dates

• First Submitted: March 7, 2016
• First Posted: March 30, 2016
• Study Start: May 4, 2016
• Primary Completion: March 9, 2020
• Study Completion: March 9, 2020
• Last Updated: August 18, 2022
• Results First Posted: August 18, 2022

Record last verified: 2022-07

Locations

US (1)