Multimodal Cue Exposure Therapy for Smoking Cessation

Multimodal CET for Smoking Cessation Augmented With D-cycloserine

At two sites (Boston University and the University of Texas at Austin, under the MPI direction of Drs. Otto and Smits) the investigators propose to randomly assign 240 adult smokers who have achieved short-term abstinence following open treatment with a 4 session cognitive-behavior therapy program combined with medication (nicotine patch, varenicline, or bupropion, selected openly) to (1) d-cycloserine augmentation of multimodal cue exposure therapy (CET), or (2) placebo augmentation of multimodal CET. This Stage II project is designed to: (1) evaluate the short-term and long-term efficacy of the experimental intervention, (2) further test putative mechanisms of change, (3) explore possible moderator effects of theoretically-relevant variables, and (4) use innovative, multimodal CET strategies. Putative mediators and smoking abstinence will be assessed during the intervention period and up to 6 months following the quit attempt.

Study Overview

• Status: Withdrawn
• Conditions: Smoking Cessation
• Intervention / Treatment: Drug: D-Cycloserine; Behavioral: Open Phase CBT that preceeds the randomization phase; Drug: Open phase smoking cessation pharmacotherapy that proceeds the randomization phase; Drug: Placebo oral tablet

Detailed Description

This study utilizes on open phase of 4-sessions of cognitive-behavior therapy for smoking cessation that is combined with open pharmacotherapy (selected by participants in collaboration with the study medical team: nicotine patch, varenicline, or bupropion). Session topics include educational (e.g., health risks of smoking, effectiveness of different treatment approaches), motivational enhancement (e.g., identifying personally relevant benefits of quitting, and costs of continuing to smoke), and cognitive-behavioral elements (e.g., identifying smoking triggers, developing coping strategies for these triggers, planning for high risk situations, relapse prevention). The study therapists will also make a supportive phone call on the day of the quit attempt, with repeated check-in calls over the quit window (i.e., weeks 4-6) as needed for individuals having difficulties reaching abstinence. Participants who fail to achieve smoking cessation during the quit period window will be referred for clinical treatment as desired in the center the study is conducted in or an alternative site.

Following successful smoking abstinence at Week 0 (Week 0 is defined by 24 hr abstinence within a two-week grace period of the target date), participants will be randomized to the study drug condition (50 mg DCS or matching placebo) combined with cue-exposure therapy (CET). CET is manualized and will have four modalities: (1) exposure to slides of smoking (pictorial), (2) exposure to emotions and imagined situations that most reliably trigger an urge to smoke (emotional/imaginal), (3) exposure to a participant's own cigarettes and pack (in vivo),70 and (4) personalized and immersive 360° VR exposure (participants select the VR scene-e.g., break time outside work, evening party, car ride that best corresponds to their highest craving situation). CET sessions are scheduled for the quit week, one week later, and again 8 weeks later. Smoking cessation assessments continue across 24 weeks of follow-up.

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: (open phase)

• daily smoker for at least one year, smoking an average of at least 10 cigarettes per day, and motivated to quit smoking (>5 on a 10 point scale)
• had reactivity to in vivo smoking cues (an increase of two points or maximal score of 10 on a 10 point visual analogue craving scale [VAS]) following no smoking for a minimum of two hours
• medical clearance to participate in the protocol

Exclusion Criteria:

• use of other tobacco products
• current unstable medical illness (i.e. deemed as at high risk of significant worsening by study intervention procedures by study physician; e.g. heart disease, chronic obstructive pulmonary disease, or seizure disorders - assessed during telephone prescreen and initial assessment), seizure disorder, pregnancy, breastfeeding, or use of isoniazid or ethionamide
• lifetime history of psychotic disorders or uncontrolled bipolar disorder, by DSM-5 criteria as assessed by the MIni International Neuropsychiatric Interview
• substance use disorder other than nicotine or caffeine active in the past 6 months, or excessive concurrent alcohol use as defined by self-report of an average of >21 standardized drinks per week for males or >14 standardized drinks per week for females
• elevated suicide risk as determined by clinician interview
• current use of any psychotropic medications or pharmacotherapy or psychotherapy for smoking cessation not provided by the investigators during the quit attempt
• known hypersensitivity to DCS
• insufficient command of the English language or inability to understand study procedures and participate in the informed consent process

To progress to the randomized phase:

• participants must achieve a 24 hour abstinence period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: D-Cycloserine Augmentation; D-cycloserine (DCS) augmentation of CET sessions	Drug: D-Cycloserine; 50 mg d-cycloserine given as an augmentation agent, 70 minutes prior to three CET sessions for participants who achieved smoking cessation following open treatment.; Other Names: DCS; Behavioral: Open Phase CBT that preceeds the randomization phase; Four sessions of weekly individual cognitive-behavior therapy (CBT: a form of psychotherapy that treats problems by helping people modify thoughts, behaviors, and emotions; in this case, for the goal of smoking cessation). Session topics include educational (e.g., health risks of smoking, effectiveness of different treatment approaches), motivational enhancement (e.g., identifying personally relevant benefits of quitting, and costs of continuing to smoke), and cognitive-behavioral elements (e.g., identifying smoking triggers, developing coping strategies for these triggers, planning for high risk situations, relapse prevention).; Drug: Open phase smoking cessation pharmacotherapy that proceeds the randomization phase; Initiating 2 weeks prior to quit date and continuing for 8 weeks after quit date, choice of one of three pharmacological smoking cessation aids: Nicotine Replacement Therapy (nicotine patch), Varenicline, or Bupropion.
PLACEBO_COMPARATOR: Placebo Augmentation; Placebo (PBO) augmentation of CET sessions	Behavioral: Open Phase CBT that preceeds the randomization phase; Four sessions of weekly individual cognitive-behavior therapy (CBT: a form of psychotherapy that treats problems by helping people modify thoughts, behaviors, and emotions; in this case, for the goal of smoking cessation). Session topics include educational (e.g., health risks of smoking, effectiveness of different treatment approaches), motivational enhancement (e.g., identifying personally relevant benefits of quitting, and costs of continuing to smoke), and cognitive-behavioral elements (e.g., identifying smoking triggers, developing coping strategies for these triggers, planning for high risk situations, relapse prevention).; Drug: Open phase smoking cessation pharmacotherapy that proceeds the randomization phase; Initiating 2 weeks prior to quit date and continuing for 8 weeks after quit date, choice of one of three pharmacological smoking cessation aids: Nicotine Replacement Therapy (nicotine patch), Varenicline, or Bupropion.; Drug: Placebo oral tablet; matching 50 mg identical placebo given as an augmentation agent, 70 minutes prior to three CET sessions for participants who achieved smoking cessation following open treatment.; Other Names: PBO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rates of Prolonged Abstinence (PA)	Failure to maintain PA at any assessment will be defined by 7 or more consecutive days of smoking or smoking at least 1 cigarette over the 2 consecutive weeks prior to the assessment	Prolonged abstinence is assessed from Quit week to Week 24 of Follow-up
Rates of Point Prevalence Abstinence (PPA)	PPA is defined as no smoking in the 7 days prior to any assessment. Self-report is verified with saliva cotinine.	Point Prevalence Abstinence is assessed from Quit Week to 24 week Follow-up using a growth curve model

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cue-Induces Patient Rating of Craving for Cigarettes	Cravings in response to visual, in vivo, imaginal, and VR smoking cues rated according to a 0 to 11 visual analogue scale; higher scores represent higher craving levels.	Post-quit weeks 0, 1, 2, 9, and 10

Collaborators and Investigators

• Sponsor: Boston University Charles River Campus
• Collaborators: National Institute on Drug Abuse (NIDA)

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): October 1, 2020
• Primary Completion (ANTICIPATED): January 31, 2021
• Study Completion (ANTICIPATED): January 31, 2021

Study Registration Dates

• First Submitted: June 19, 2019
• First Submitted That Met QC Criteria: July 25, 2019
• First Posted (ACTUAL): July 29, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 12, 2021
• Last Update Submitted That Met QC Criteria: February 10, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antimetabolites; Anti-Bacterial Agents; Antitubercular Agents; Antibiotics, Antitubercular; Anti-Infective Agents, Urinary; Renal Agents; Cycloserine
• Other Study ID Numbers: R01DA048043

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: One year after publication of the primary aims from this project the primary and fully de-identified IPD will be made available by the investigators on CD for other researchers providing documented IRB consent from their institution.
• IPD Sharing Time Frame: One year after publication of primary aims
• IPD Sharing Access Criteria: Institutional IRB approval
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ANALYTIC_CODE

Drug and device information, study documents

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