Cognitive and Affective Mechanisms Underlying an Olfactory Approach to Modify Cigarette Craving

NCT04902469 | Recruiting DMC

• 2 other identifiers: STUDY20070045R01AT010896-01
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed study uses fMRI and behavioral measures in and outside the laboratory to investigate the neurobehavioral mechanisms underlying the impact of pleasant olfactory cues (OCs) on cigarette craving. The investigators plan to randomize 278 participants to a pleasant OC condition or an odor blank (neutral) condition and due to anticipated drop out expect to run 250 adult (half female) smokers, including both daily and nondaily smokers through the protocol. This study involves three visits. In the first visit, participants will complete a baseline breath carbon monoxide reading, a brief odor threshold test, and complete a series of self-report measures. In the next session, participants who are 8-hrs deprived of nicotine will undergo a 60-minute fMRI scan that will include structural, resting state, and task-based data collection. The fMRI task involves completing a series of tasks designed to index responses linked to key neural networks found to relate to addiction (e.g., reward processing, working memory). Participants will also be exposed to smoking cues to heighten craving and then depending on their condition (randomly assigned) will either receive a pleasant or neutral (odor blank) OC. In the third session, behavioral data will be collected to test the impact of either a pleasant or neutral OC on cigarette craving using self-reported urge and behavioral measures linked to craving. Finally, for pilot purposes designed to offer data for a subsequent clinical study (beyond this study), participants will additionally complete a 7-day ecological momentary assessment (EMA) protocol in which they will monitor cigarette craving and initial data will be collected outside the laboratory to evaluate the impact of OCs on naturally occurring craving. It is hypothesized that pleasant OCs will disrupt craving brain states and attenuate craving (as compared to neutral olfactory cues). Further, it is hypothesized that individual variation in neural responses to cognitive and affective tasks will reveal variation in mechanisms underlying pleasant OC craving reduction and that individual differences will moderate pleasant OC-induced craving relief. Finally, it is also expected that emotional responses to pleasant OCs will mediate the impact of OCs on craving and smoking-related processes.

Conditions

Craving

Keywords

Craving; Olfaction; mechanistic study

Outcome Measures

Primary Outcomes (2)

• Disruption of the Craving Brain State by the Pleasant, Compared to the Neutral, Olfactory Cue

  Condition difference in the Fisher Z-transformed correlation coefficient between the craving brain state and olfactory cue-induced brain state, where brain states are indexed as the fMRI contrast between cigarette cue (with, and without, odor) and control cue

  within 1 month of enrollment; immediately before and after administration of the olfactory cue

• Craving Observed During Pleasant Compared to Neutral OC Exposure Assessments, Controlling for Pre-OC Craving Ratings

  Condition difference in self-reported urge on a 0 to 100 scale, with 0 equal to no urge to smoke at all, and 100 as the "strongest urge to smoke that I have ever felt"

  between 1 and 10 days subsequent to the fMRI study visit; before and immediately after administration of the olfactory cue

Secondary Outcomes (3)

• Strength of the Cognitive-Associated Neural Fingerprint Induced During the Pleasant Compared to Neutral Olfactory Cue

  within 1 month of enrollment; during the fMRI scan

• Change in Craving from Peak Craving to the Craving Observed During Pleasant, Compared to Neutral, Olfactory Cues as Measured by a Pressure-Sensitive Squeeze Device

  between 1 and 10 days subsequent to the fMRI study visit; immediately before and after administration of the olfactory cue

• Mediating Role of the Emotional Response to the Pleasant Olfactory Cue, as Indexed by the Facial Action Coding System, on the Impact of Pleasant Olfactory Cues on Self-Reported Craving

  between 1 and 10 days subsequent to the fMRI study visit; immediately before and after administration of the olfactory cue

Study Arms (2)

Pleasant Odor

EXPERIMENTAL

Participants in this condition will sniff the olfactory cue they rate as both pleasant (\>5 on the 1-9 scale) and the most intense following cigarette cue exposure. If this odor is the same as their self-reported preferred e-cigarette flavor, we will choose the next most intense odor out of the odors rated as pleasant.

Behavioral: Pleasant Odor

Odor Blank

OTHER

Participants in this condition will sniff a neutral olfactory cue (odor blank) following cigarette cue exposure.

Behavioral: Odor Blank

Interventions

Pleasant Odor BEHAVIORAL

Each participant in the pleasant odor condition will sniff an odor that they rated as the most intense out of a sample of odors rated to be pleasant. If this odor is the same as their self-reported preferred e-cigarette flavor, we will choose the next most intense odor out of the odors rated to be pleasant. Odors are generic and commercially available in supermarkets such as vanilla, coconut, and chocolate. Importantly, the investigators are not testing the specific odors, rather the participant's idiosyncratic response to a menu of odors. In other words, the key is that each participant in the experimental condition receives the odor that they like the best, regardless of which one it is.

Pleasant Odor

Odor Blank BEHAVIORAL

Each participant in the odor blank condition will sniff a neutral olfactory cue (odor blank). This involves a container with no added scent. This serves as the control condition.

Odor Blank

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 18-49
• Right-handed
• Fluent in English
• Intact sense of smell
• Pass an MRI safety screening and along these lines will need to be 250lbs or less to safely enter the MRI
• No drug dependence outside of nicotine or caffeine
• Must fit into one of two categories of smokers, daily or nondaily, as confirmed by verbal self-report and a baseline CO reading; Daily smokers: must smoke 10-30 cigarettes per day for at least 12 months, Nondaily smokers: must smoke for 1-14 days of the last 30 days with no more than 20 cigarettes a day
• Need to have access to a working smartphone to complete the ecological momentary assessment portion of the study

You may not qualify if:

• Medical conditions that contraindicate nicotine use
• Not fluent in English
• Illiterate
• Current neurological or psychotic disorders
• Current psychoactive drug use
• MRI contraindications such as stroke history, pregnancy, metal in the body, history of aneurysms, or serious head injury
• Individuals will also be excluded if they report any allergies to the odors used in our study.
• Baseline CO readings will need to be consistent with our criteria for daily and nondaily smokers for participants to be considered eligible. Specifically, we plan to rule out extremely heavy smokers (nondeprived CO \> 55, for whom the smoking abstinence requirement may be too extreme to allow a sensitive test of our OC manipulation) and daily smokers with a nondeprived CO reading \<10 PPM as this would raise concerns that they do smoke enough to be classified as a daily smoker.

Sponsors & Collaborators

• University of Pittsburgh: lead
• National Center for Complementary and Integrative Health (NCCIH): collaborator

Study Sites (1)

The University of Pittsburgh

Pittsburgh, Pennsylvania, 15260, United States

RECRUITING

Related Publications (2)

• Sayette MA, Marchetti MA, Herz RS, Martin LM, Bowdring MA. Pleasant olfactory cues can reduce cigarette craving. J Abnorm Psychol. 2019 May;128(4):327-340. doi: 10.1037/abn0000431. Epub 2019 Apr 15.

  PMID: 30985171 BACKGROUND

• Sayette MA, Parrott DJ. Effects of olfactory stimuli on urge reduction in smokers. Exp Clin Psychopharmacol. 1999 May;7(2):151-9. doi: 10.1037//1064-1297.7.2.151.

  PMID: 10340155 BACKGROUND

MeSH Terms

Conditions

Anosmia

Condition Hierarchy (Ancestors)

Olfaction Disorders; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Michael A Sayette, PhD

  The University of Pittsburgh

  PRINCIPAL INVESTIGATOR

• Marc N Coutanche, PhD

  The University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michael A Sayette, PhD

CONTACT

412-624-8799; sayette@pitt.edu

Marc N Coutanche, PhD

CONTACT

(412) 624-7458; marc.coutanche@pitt.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participants will not be informed about whether they are in the odor blank (control) or pleasant odor (experimental) group. However, the odor blank group is intended to control for the act of sniffing rather than the belief that one has sniffed a pleasant odor.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychology

Model Details: This is a between-subjects design in which 250 nicotine-deprived smokers, who vary in whether they smoke daily and in motivation to quit, will be exposed to smoking cues to induce peak cravings and then receive either a pleasant (n = 125) or neutral (n = 125) olfactory cue.

Study Record Dates

• First Submitted: May 17, 2021
• First Posted: May 26, 2021
• Study Start: December 1, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: July 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Study methods, hypotheses, and primary planned analyses will be pre-registered on the Open Science Framework (OSF) prior to data collection. Subsequent to publication of papers based on data pertaining to this investigation's specific aims, de-identified data will be made available for the purposes of research upon access request.
• Access Criteria: De-identified study data will be available to researchers who agree to a data-sharing agreement that provides for (1) a commitment to using the data only for noncommercial research purposes and (2) a commitment to securing the data using appropriate computer technology. Unthresholded fMRI statistical maps will be publicly available to all users on NeuroVault.

Locations

US (1)