Novel Pharmacotherapy Approaches in Smokers With Serious Mental Illness

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Schizoaffective Disorder; Bipolar Disorder; Nicotine Dependence
• Intervention / Treatment: Drug: Varenicline

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 Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Benjamin McKenna, PhD; Phone Number: 858-534-8817; Email: bmckenna@ucsd.edu

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • Pacific Treatment & Research Center at UCSD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of Combining ACT With 2 Different Varenicline-assisted Quitting Strategies	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)	Through completion of study, an average of 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Explore whether nicotine metabolism influences medication tolerability	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	Through completion of study, an average of 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nicotine Metabolite Ratio (NMR) Exploratory Aim	The nicotine metabolite ratio (NMR) as measured by the ratio of 3'-hydroxycotinine (the breakdown product of cotinine) divided by the concentration of cotinine (the breakdown product of nicotine) in a smoker's serum is a biomarker of nicotine clearance. Other researchers have found that a person's NMR might influence one's response to certain smoking cessation medications. The NMR was measured in serum using electrospray ionization liquid chromatography tandem mass spectrometry technology.	Through completion of study, an average of 2 years

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Collaborators: University of California; Veterans Medical Research Foundation

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2019
• Primary Completion (Actual): March 4, 2022
• Study Completion (Actual): March 4, 2022

Study Registration Dates

• First Submitted: June 25, 2019
• First Submitted That Met QC Criteria: July 5, 2019
• First Posted (Actual): July 8, 2019

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Acceptance and Commitment Therapy; schizophrenia; smoking cessation; varenicline; nicotine; bipolar; cigarette; schizoaffective
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Substance-Related Disorders; Mood Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Bipolar and Related Disorders; Schizophrenia; Psychotic Disorders; Mental Disorders; Tobacco Use Disorder; Bipolar Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Nicotinic Agonists; Cholinergic Agonists; Varenicline
• Other Study ID Numbers: 180785

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes