Balanced Placebo Design With Varenicline: Pharmacological and Expectancy Effects on Medication Adherence

Varenicline Pharmacological and Expectancy Effects on Medication Adherence (Balanced Placebo Design With Varenicline: Pharmacological and Expectancy Effects on Medication Adherence)

The current study will use the double-blind balanced placebo design to examine differences between expectancies versus the pharmacological effects of varenicline medication administered for two weeks to cigarette smokers. The double-blind balanced placebo design includes medication administration (active medication v. placebo) and medication information (told truth v. deception) resulting in four groups of smokers: (1) told therapeutic dose (TD) medication + received TD medication; (2) told TD medication + received placebo; (3) told low dose (LD) medication+ received TD dose medication; (4) told LD medication + received placebo. Ecological momentary assessments (EMA) in the form of Daily Dairies delivered via smartphone will assess real-time side effects, withdrawal symptoms, cigarettes smoked, medication use, and reasons for medication non-adherence.

Study Overview

• Status: Completed
• Conditions: Medication Adherence
• Intervention / Treatment: Drug: Varenicline; Other: Placebo

Detailed Description

The current proposal will utilize the double-blind balanced placebo design to differentiate expectancies versus pharmacologic mechanisms of varenicline administered to varenicline naïve smokers seeking treatment (N = 80) for two-weeks. Race block randomization (controlling for baseline expectancies) will be used to randomize participants. The double-blind balanced placebo design includes a cross-balanced medication administration (active medication v. placebo) and instructional set (told truth v. deception) resulting in four groups of smokers seeking treatment (n = 20 for each): (1) told therapeutic dose (TD) medication + received TD medication; (2) told TD medication + received placebo; (3) told low dose (LD) medication+ received TD dose medication; (4) told LD medication + received placebo. Participants will be told they received low dose (rather than placebo) due to concerns that participants will not take a medication that they believe to be a placebo. Ecological momentary assessments (EMA) in the form of Daily Dairies delivered via smartphone will assess real-time side effects, withdrawal symptoms, cigarettes smoked, medication use, and reasons for medication non-adherence. The current proposal will test the following specific aims:

Specific Aim 1: Examine the main effects of instructional set and pharmacology. Hypothesis 1: Main effects for TD instructional set and active medication administration will result in reduced medication adherence compared with LD instructional set and placebo medication.

Specific Aim 2: Examine the interaction between instructional set and pharmacology. Hypothesis 2: There will be a synergistic (i.e., non-additive) effect between instructional set and pharmacology. Specifically, those assigned to the TD instructional set and active medication group will result in a 50% discontinuation compared to a 20% discontinuation in the TD instructional set and placebo medication group.

Exploratory Aim: Evaluate moderators of pharmacology and expectancy effects on medication adherence. First, we will conduct exploratory examination of baseline medication expectancies moderating the relationship between pharmacology and medication adherence. Second, we will conduct an exploratory evaluation of potential moderators (e.g., gender and race) of pharmacology and baseline medication expectancy.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 years or older
• Smoking at least 5 cigarettes per day (cpd) for the past year
• A carbon monoxide (CO) >10ppm
• English speaking
• Must own a cellphone with SMS text capacity with Internet access OR daily use of email
• Must be varenicline naïve
• Express a desire to quit smoking

Exclusion Criteria:

• Living in a restricted environment (e.g., prison or jail facility, etc.)
• Pregnant or nursing
• Currently enrolled in a smoking cessation treatment program, using NRT products, or prescribed bupropion or varenicline
• Known allergy to varenicline
• History of kidney disease, dialysis or known kidney impairment
• Cognitive impairment or unstable psychiatric condition that interferes with the informed consent process (individuals stable on psychiatric medications will be included)
• Daily or exclusive use of other tobacco products
• Current suicidal or homicidal ideation or a suicidal attempt within the past 12 months
• History of stroke, heart attack, or seizures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Therapeutic Dose Truth; told therapeutic dose medication + received therapeutic dose medication	Drug: Varenicline; Participants will be provided varenicline medication
Placebo Comparator: Therapeutic Dose Deception; told therapeutic dose medication + received placebo	Other: Placebo; Participants will be provided placebo medication
Active Comparator: Low Dose Vareniclince Deception; told low dose medication + received therapeutic dose medication	Drug: Varenicline; Participants will be provided varenicline medication
Placebo Comparator: Low Dose Placebo Deception; told low dose medication + received placebo	Other: Placebo; Participants will be provided placebo medication

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Medication Adherence	Self-reported medication adherence measured through a single item assessing medication compliance. The item is answered as "yes" (scored as 1) or "no" (scored as 0). This measure combines all responses from Day 1 through Day 13 of this study to provide a total measure of medication adherence ranging from 0% (missed all doses) to 100% (took every dose as prescribed). Higher scores indicate better outcomes (i.e., better adherence to medication).	Days 1 - 13

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Medication Expectancies	Medication expectancies will be measured through the Beliefs and Attitudes about Varenicline (BAV) scale which is a 6-item questionnaire adapted to assess varenicline expectancies. This measure is rated on a scale from 1 (not at all) to 5 (extremely). The measure has a minimum score of 6 and a maximum score of 30. Higher scores indicating better outcomes (i.e., stronger positive beliefs about using varenicline).	Baseline and Day 14

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side Effects	A 30-item self-report measure of the presence (or not) of symptoms commonly associated with varenicline side effects and nicotine withdrawal. Items are rated as "No" (scored as 0) or "Yes" (scored as 1). A total score was calculated to reflect the total number of reported side effects. This measure has a minimum score of 0 and a maximum score of 30. Higher scores indicate worse outcomes (i.e., greater frequency of experienced side effects).	Day 14

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2018
• Primary Completion (Actual): October 29, 2019
• Study Completion (Actual): October 29, 2019

Study Registration Dates

• First Submitted: May 15, 2018
• First Submitted That Met QC Criteria: May 24, 2018
• First Posted (Actual): May 29, 2018

Study Record Updates

• Last Update Posted (Actual): December 14, 2020
• Last Update Submitted That Met QC Criteria: November 17, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Nicotinic Agonists; Cholinergic Agonists; Varenicline
• Other Study ID Numbers: IRB-300001404

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

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.: No