Bipolar Disorder, Nicotine Dependence, Schizoaffective Disorder, Schizophrenia
Conditions
Keywords
nicotine, varenicline, Acceptance and Commitment Therapy, schizophrenia, schizoaffective, bipolar, smoking cessation, cigarette
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.
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.
Interventions
DRUGVarenicline
The ten 30-minute sessions will target core processes in ACT such as acceptance and being present.
Sponsors
Veterans Medical Research Foundation
University of California
University of California, San Diego
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Everyone, with the exception of the study pharmacist, will be blinded to which arm participants will be randomized into.
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Nicotine Metabolite Ratio (NMR) Exploratory Aim | Through completion of study, an average of 2 years | 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. |
Countries
United States
Participant flow
Pre-assignment details
The protocol defined all participants who signed a written informed consent and who completed a formal screening process as Enrolled in the trial. Thus, following CONSORT diagram terminology, there were N = 39 enrollees. 28 participants were randomized into one of the two treatment arms and were thus allocated to treatment.
Participants by arm
| Arm | Count |
|---|---|
| Low Dose Varenicline 0.5 mg twice daily with 0.5 mg daily titration over one full week
Varenicline: The ten 30-minute sessions will target core processes in ACT such as acceptance and being present. | 14 |
| Standard Dose Varenicline 1.0 mg twice daily with standard titration
Varenicline: The ten 30-minute sessions will target core processes in ACT such as acceptance and being present. | 14 |
| Total | 28 |
Baseline characteristics
| Characteristic | Low Dose Varenicline | Standard Dose Varenicline | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 14 Participants | 27 Participants |
| Age, Continuous | 50 years STANDARD_DEVIATION 9.8 | 45.6 years STANDARD_DEVIATION 11.6 | 47.8 years STANDARD_DEVIATION 10.8 |
| Cigarettes Per Day | 14.5 Cigarettes STANDARD_DEVIATION 3.3 | 25.2 Cigarettes STANDARD_DEVIATION 11 | 19.8 Cigarettes STANDARD_DEVIATION 9.7 |
| Diagnosis: Bipolar Disorder (BD) or Schizophrenia Spectrum Disorder (SSD) BD | 7 Participants | 8 Participants | 15 Participants |
| Diagnosis: Bipolar Disorder (BD) or Schizophrenia Spectrum Disorder (SSD) SSD | 7 Participants | 6 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 13 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Fagerström Test for Cigarette Dependence | 5.4 units on a scale STANDARD_DEVIATION 1.6 | 6.8 units on a scale STANDARD_DEVIATION 2 | 6 units on a scale STANDARD_DEVIATION 1.9 |
| Hospital Anxiety and Depression Scale (HADS) HADS: Anxiety | 9.6 units on a scale STANDARD_DEVIATION 5.9 | 12 units on a scale STANDARD_DEVIATION 6.6 | 10.8 units on a scale STANDARD_DEVIATION 6.3 |
| Hospital Anxiety and Depression Scale (HADS) HADS: Depression | 4.4 units on a scale STANDARD_DEVIATION 3.9 | 6.5 units on a scale STANDARD_DEVIATION 5.5 | 5.4 units on a scale STANDARD_DEVIATION 4.8 |
| Minnesota Nicotine Withdrawal Scale | 20.9 units on a scale STANDARD_DEVIATION 12.4 | 23.5 units on a scale STANDARD_DEVIATION 12.3 | 22.2 units on a scale STANDARD_DEVIATION 12.2 |
| Questionnaire of Smoking Urges- Brief | 51.1 units on a scale STANDARD_DEVIATION 15 | 51.7 units on a scale STANDARD_DEVIATION 15.1 | 51.4 units on a scale STANDARD_DEVIATION 14.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 6 Participants | 14 Participants |
| Region of Enrollment United States | 14 Participants | 14 Participants | 28 Participants |
| Sex: Female, Male Female | 6 Participants | 7 Participants | 13 Participants |
| Sex: Female, Male Male | 8 Participants | 7 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 14 |
| other Total, other adverse events | 13 / 14 | 12 / 14 |
| serious Total, serious adverse events | 0 / 14 | 1 / 14 |
Outcome results
Primary
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)
Time frame: Through completion of study, an average of 2 years
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Low Dose Varenicline | Feasibility of Combining ACT With 2 Different Varenicline-assisted Quitting Strategies | Demand For Participating | 1 Participants |
| Low Dose Varenicline | Feasibility of Combining ACT With 2 Different Varenicline-assisted Quitting Strategies | Practicality of Study Procedures | 9 Participants |
| Low Dose Varenicline | Feasibility of Combining ACT With 2 Different Varenicline-assisted Quitting Strategies | Acceptability of Study Procedures | 13 Participants |
| Standard Dose Varenicline | Feasibility of Combining ACT With 2 Different Varenicline-assisted Quitting Strategies | Demand For Participating | 1 Participants |
| Standard Dose Varenicline | Feasibility of Combining ACT With 2 Different Varenicline-assisted Quitting Strategies | Practicality of Study Procedures | 12 Participants |
| Standard Dose Varenicline | Feasibility of Combining ACT With 2 Different Varenicline-assisted Quitting Strategies | Acceptability of Study Procedures | 12 Participants |
Other Pre-specified
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.
Time frame: Through completion of study, an average of 2 years
Population: Due to the small sample size and our finding that practically all smokers in this sample of persons with serious mental illness would be considered normal metabolizers based on population normative values, Arms/Groups were combined to maximize power and to explore whether there was any correlation between the NMR values and the incidence of adverse events. Since this was an exploratory aim, the analysis was pre-specified to include all participants regardless of varenicline condition.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose Varenicline | Nicotine Metabolite Ratio (NMR) Exploratory Aim | 1.20 ratio of molar concentrations | Standard Deviation 0.75 |