Novel Pharmacotherapy Approaches in Smokers With Serious Mental Illness

Sponsor

University of California, San Diego (Other)

Overall Status

Recruiting

CT.gov ID

NCT04011280

Collaborator

Veterans Medical Research Foundation (Other), University of California (Other)

Enrollment

Location

Arms

44.5

Anticipated Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Approximately 60 chronic smokers with bipolar disorder, schizophrenia or schizoaffective disorder who are motivated to try to quit smoking will be randomized to receive smoking cessation treatment with the FDA-approved medication, varenicline, delivered either a) at its standard dose and titration schedule (half of the participants) versus b) at a lower dose and slower titration schedule (the other half), for 12 weeks. All smokers will choose a target quit date sometime between 8 to 35 days after starting the medication. All participants will receive ten 30-minute sessions of a behavioral treatment called Acceptance and Commitment Therapy (ACT). Participants will be followed for an additional 12 weeks off study medication. The major endpoint is the feasibility of combining ACT with the different dosing strategies. Investigators will also conduct a blood test that measures the breakdown of nicotine in the body to explore whether that measure influences treatment response and side effects.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder Schizophrenia Schizoaffective Disorder Nicotine Dependence	Drug: Varenicline	Phase 4

Detailed Description

This pilot feasibility trial is a Phase IV, 12-week, single center, randomized, double blind, parallel group comparison of low (0.5 mg twice daily with slower titration over one full week) versus standard dose (1.0 mg twice daily with standard titration) varenicline in individuals with DSM-V Bipolar Disorder (BD) or Schizophrenia Spectrum Disorders (SSD) with a 12-week, post-treatment follow-up. The 16 visits after screening (Weeks 0-24) include 11 in-person (with medications dispensed at weeks 0, 2, 4, 6, 8 and 10] and 5 via telephone. Plasma will be obtained at baseline to measure participants' Nicotine Metabolite Ratio (NMR) and to identify slow versus normal nicotine metabolisers. A flexible quit date (between days 8-35) will be employed allowing varenicline preloading to occur prior to the Target Quit Date. Ten sessions of Acceptance & Commitment Therapy (ACT) for smoking cessation will be delivered by trained counselors.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This pilot trial is a Phase IV, 12-week, single center, randomized, double blind, parallel group comparison of low (0.5 mg twice daily with slower titration over one full week) versus standard dose (1.0 mg twice daily with standard titration) varenicline in individuals with DSM-V BD or SSD with a 12-week, post-treatment follow-up.This pilot trial is a Phase IV, 12-week, single center, randomized, double blind, parallel group comparison of low (0.5 mg twice daily with slower titration over one full week) versus standard dose (1.0 mg twice daily with standard titration) varenicline in individuals with DSM-V BD or SSD with a 12-week, post-treatment follow-up.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Everyone, with the exception of the study pharmacist, will be blinded to which arm participants will be randomized into.

Primary Purpose:

Treatment

Official Title:

Novel Pharmacotherapy Approaches in Smokers With Serious Mental Illness

Actual Study Start Date :

Jul 15, 2019

Anticipated Primary Completion Date :

Sep 30, 2022

Anticipated Study Completion Date :

Mar 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Low Dose Varenicline 0.5 mg twice daily with 0.5 mg daily titration over one full week	Drug: Varenicline The ten 30-minute sessions will target core processes in ACT such as acceptance and being present. Other Names: Acceptance and Commitment Therapy
Active Comparator: Standard Dose Varenicline 1.0 mg twice daily with standard titration	Drug: Varenicline The ten 30-minute sessions will target core processes in ACT such as acceptance and being present. Other Names: Acceptance and Commitment Therapy

Arm

Intervention/Treatment

Experimental: Low Dose Varenicline

0.5 mg twice daily with 0.5 mg daily titration over one full week

Drug: Varenicline

The ten 30-minute sessions will target core processes in ACT such as acceptance and being present.

Other Names:

Acceptance and Commitment Therapy

Active Comparator: Standard Dose Varenicline

1.0 mg twice daily with standard titration

Drug: Varenicline

The ten 30-minute sessions will target core processes in ACT such as acceptance and being present.

Other Names:

Acceptance and Commitment Therapy

Outcome Measures

Primary Outcome Measures

Feasibility of combining ACT with 2 different varenicline-assisted quitting strategies [Through completion of study, an average of 2 years]
Demand for participating (# of participants recruited per month); practicality of study procedures (% participants completing study procedures); acceptability of study procedures (% participants adhering to making a quit attempt within the quit window)

Secondary Outcome Measures

Explore whether nicotine metabolism influences medication tolerability [Through completion of study, an average of 2 years]
Nicotine metabolite ratio (ratio of trans-3'-hydroxycotinine / cotinine in plasma) in relation to adverse events (volunteered, observed or solicited adverse events occurring during study treatment + 30 days). Slow nicotine metabolisers will be compared with normal nicotine metabolisers on the incidence (% who experienced) adverse events

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

18-70 years of age
Outpatients with a DSM-V diagnosis of Bipolar Disorder or Schizophrenia Spectrum Disorder
Smoke at least 10 cigarettes per day and have an expired carbon monoxide (CO) breathalyzer of ≥ 10 ppm at screening and baseline visits
Are motivated to quit smoking
Have access to a mental health provider

Exclusion Criteria:

Females who are pregnant, planning to become pregnant, or lactating
Test positive for any non-prescribed medications or illicit drugs
Have made a suicide attempt or engaged in self-mutilatory behavior in the past year
Meet criteria for another Substance Use Disorder in the past month
In the investigators' judgement, are either psychiatrically or medically unstable to safely participate
Are currently using any other form of treatment for smoking cessation