Clinical trial NCT03538808
Conditions: Medication Adherence
Sponsor: University of Alabama at Birmingham
Start date: 2018-11-06; Completion date: 2019-10-29
Enrollment: 80 participants; Allocation: RANDOMIZED; Intervention model: FACTORIAL

Brief summary:
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.

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.

Arms: arm 1: told therapeutic dose medication + received therapeutic dose medication arm 2: told therapeutic dose medication + received placebo arm 3: told low dose medication + received therapeutic dose medication arm 4: told low dose medication + received placebo
Interventions: intervention 1: Varenicline intervention 2: Placebo
Intervention descriptions: intervention 1: Participants will be provided varenicline medication intervention 2: Participants will be provided placebo medication

Protocol documents:
Prot_SAP_001.pdf: 
 
 
 
 
Balanced Placebo Design With Varenicline: Pharmacological and Expectancy Effects on 
Medication Adherence 
NCT03538808 
12/05/17 
Samantha Schiavon, M.A. 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
Study Protocol 
 
All eligible participants completed baseline measures to determine tobacco history, 
medication expectancies, side effects, and smoking cessation outcomes (i.e., cravings, 
withdrawal, cessation fatigue, etc.). Following completion of the study questionnaires, 
participants were randomized into either: (1) told therapeutic dose (TD) medication + received 
varenicline; (2) told TD medication + received placebo; (3) told low dose (LD) medication + 
received varenicline; (4) told LD medication + received placebo. Randomization into one of the 
four conditions was balanced on race/ethnicity (African American or Caucasian) and baseline 
negative medication expectancies as measured on the Stanford Expectations of Treatment 
Scale (dichotomized as  ≤ 3.7 or  ≥ 3.8). 
Once participants were randomized, they were provided with a two-week blister 
package of varenicline medication or matched placebo and given scripted instructions for either 
the low dose or therapeutic dose condition (see below).  Additionally, all participants engaged 
in brief smoking cessation counseling (~15 minutes) and were provided a one-page tip sheet 
with cognitive and behavioral strategies to quit smoking.  
 
Low Dose Instructions: “You will be receiving an extremely low dose of Chantix. You will 
experience some benefit from taking this dose, but should not experience side effects.”  


Therapeutic Dose Instructions: “You will be receiving a therapeutic standard dose of Chantix. 
You will experience maximum benefit from taking this dose, but may experience greater side 
effects.”  
 
 
All participants were instructed to take their first medication dose immediately 
following their baseline appointment and proceed with the standard titration schedule: Days 1 
– 3 (0.5mg/daily), Days 4 – 7 (0.5mg/BID), Days 8+ (1 mg/BID). On days 1 – 13, participants 
completed ecological momentary assessments through a once-daily electronic “daily diary”. 
This daily diary assessment was completed through a secure link on either their cellular phone 
or computer based on individual preferences. All participants were also given paper calendars 
as a backup method to collect data on daily medication adherence and cigarette use in the 
event they experience changes in cellular data coverage, internet accessibility, or technical 
issues with the data collection software.  
 
On day 14 participants completed their final appointment and were instructed to bring 
their medication blister packages for adherence verification. Additionally, participants 
completed study questionnaires regarding side effects and smoking cessation outcomes. After 
all assessments were completed participants were engaged in a study manipulation check, in 
which they were told that deception was used on some of the participants and they would earn 
$1 if they could correctly guess whether or not they received a low or therapeutic dose of 
varenicline. The dollar compensation was meant to motivate a thoughtful guess, but was 
provided to the participants regardless of their answer. Following the manipulation check, all 
participants were provided with private debriefing information in an enclosed envelope to 


ensure the study could remain double-blind. In addition to receiving $10 for completing the 
baseline appointment, study compensation was administered based on the percentage of daily 
diaries completed: at least 50% ($20), at least 80% ($40), and 90% or higher ($50).  
 
Planned Analysis 
A total of 76 participants completed at least 3 waves of data and were included in the 
Generalized Estimating Equations (GEE) model to evaluate Specific Aims 1 and 2. Time was 
structured daily for the 14-day medication regimen as assessed through the daily diaries. The 
outcome variable for medication adherence was dichotomized as Yes (coded 1) or No (coded 0). 
The GEE model was specified to predict medication adherence (i.e., “Yes” responses). All GEE 
models were conducted utilizing an exchangeable correlation matrix and binomial distribution 
with a logit link function. To evaluate the Exploratory Aim, a series of moderation analyses were 
conducted utilizing the PROCESS macro for SPSS.   
Additionally, two statistical analyses were conducted to examine a possible association 
between the interaction effect of the study manipulations (medication received and 
instructional set) as it relates to experienced side effects and medication adherence. First, a 
repeated measures ANOVA was utilized to examine the interaction effect of medication 
received and instructional set on experienced side effects. Secondly, a moderated moderation 
analysis using a three-way interaction was conducted to examine if the interaction between 
medication received (varenicline v. placebo) and instructional set (therapeutic v. low dose) has 
a significant effect on the relationship between side effects and medication adherence.