Nicotine Use DisorderSITNCT03438188
Neural Basis of Eating Behavior in Abstinent Smokers
A study testing Practice Quit Attempt in people with Nicotine Use Disorder, run by University of Pennsylvania at 1 site in United States.
Trial summary
The purpose of this research study is to better understand why people gain weight when they quit smoking by examining food intake and changes in brain activity in smokers when they are smoking as usual compared to when they have been deprived of cigarettes (i.e., have not smoked for 4 days) as compared to a non-smoker… Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Nicotine Use Disorder
- What is being tested?
- Practice Quit Attempt
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 82 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2018to 30 Aug 2023
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male and female participants who are between 18 and 45 years of age.
- Smoking group - 80 treatment-seeking smokers who self-report smoking at least 10 cigarettes (menthol and/or non-menthol) per day for at least the last 6 months. Smoking status will be confirmed by CO greater than or equal to 8 parts per million (ppm) at the Intake Visit.
- Non-smoking group - 30 individuals reporting fewer than 100 lifetime cigarettes and not even a puff of a cigarette for a minimum of 2 years. Smoking status of non-smokers will be confirmed by CO less than 5ppm. They will be matched to the smoker group on age, sex, and education.
- Plan to live in the area for the duration of the study (i.e. ~8 weeks/2 months).
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the combined consent and HIPAA form.
- Smokers who wish to make a permanent quit attempt in the next 1-2 months (treatment-seeking), because our prior work suggests that motivated subjects are more sensitive to medication effects on smoking behavior. Using a scale from 0 to 100 (100, being extremely interested), subjects must rate their interest in quitting smoking within the next 1-2 months greater than 50.
- Able to communicate fluently in English (i.e. speaking, writing, and reading).
Who cannot join
- Subjects who present and/or self-report with the following criteria will not be eligible to participate in the study:
- Smoking Behavior
- Regular use of nicotine-containing products other than cigarettes (e.g. chewing tobacco, snuff, snus, cigars, e-cigs, etc.). Participants agreeing to abstain from using nicotine- containing products other than cigarettes will be considered eligible.
- Current enrollment or plans to enroll in another research and/or smoking cessation program over the duration of the study (i.e. ~8 weeks/2 months).
- Anticipated use (within the next ~8 weeks/2 months) of any nicotine substitutes and/or smoking cessation treatments/medications unless provided through the study.
- Provide a CO breath test reading less than 8 ppm at Intake Visit (smokers) or greater than 5ppm at intake visit (non-smokers).
Show all 66Show fewer
- Alcohol and Drug
- History of substance abuse (other than nicotine) in the past 12 months and/or currently receiving medical treatment for substance abuse. Counseling and support groups (e.g. Alcoholics Anonymous and Narcotics Anonymous) will not be considered medical treatment for the purposes of this protocol.
- Current alcohol consumption that exceeds 25 standard drinks/week.
- Breath alcohol reading (BrAC) greater than .000 at the Intake Visit.
- A positive urine drug screen (UDS) for cocaine, opiates, amphetamines, methamphetamines, phencyclidine (PCP), ecstasy (MDMA), barbiturates, benzodiazepines, methadone, and/or oxycodone at the Intake Visit.
- Medical
- Women who are pregnant, breast feeding, or planning a pregnancy over the duration of the study period. Women must agree to use an adequate form of contraception or abstain from sexual intercourse for the duration of the study.
- Current treatment of cancer or diagnosed with cancer (except basal or squamous-cell carcinoma not treated with chemotherapy and/or radiation) in the past 6 months.
- Poorly controlled, brittle, or pump-dependent Type I diabetes.
- Current peptic ulcer bleeding.
- Active hepatitis or poorly controlled kidney and/or liver disease.
- Serious or unstable disease within the past 6 months. Notable diseases will be evaluated on a case-by-case basis by the Principal Investigator and/or the Study Physician.
- Any impairment including, but not limited to, visual, physical, and/or neurological impairments preventing proper completion of the study procedures. Notable impairments will be evaluated on a case-by-case basis by the Principal Investigator and/or the Study Physician.
- Applicable food allergies or disorders:
- Galactosemia a
- Notable milk allergy (lactose intolerant participants may proceed unless they experience severe symptoms) b
- Notable soy allergy c
- Peanut allergy d a,b,c Boost® Original Very Vanilla Nutritional Shake: Contains milk and soy ingredients. Suitable for Lactose Intolerance.
- b,c,d M\&M's® (Milk Chocolate): Contains milk and soy ingredients (MAY CONTAIN PEANUTS) Lay's® Classic Potato Chips (Gluten Free): Potatoes, vegetable oil, and salt
- Psychiatric
- Current diagnosis of major depression. Subjects with a history of major depression, in remission for 6 months or longer (may be stable on antidepressant medications), are eligible.
- Lifetime history of a suicide attempt.
- Lifetime history of schizophrenia, psychosis, and/or bipolar disorder.
- Current diagnosis of Attention Deficit/Hyperactivity Disorder (ADHD).
- Current diagnosis of bulimia, anorexia nervosa or binge eating.
- Medication
- Current use or recent discontinuation (within the last 14 days) of:
- Smoking cessation medication (e.g., Zyban, Wellbutrin, Wellbutrin SR, Chantix).
- Benzodiazepines and/or Barbiturates.
- Anti-psychotic medications.
- Prescription stimulants (e.g., Provigil, Ritalin, Adderall).
- Systemic steroids.
- Medications for the use of addiction treatment.
- Current use of:
- Nicotine replacement therapy (NRT).
- Heart medications such as digoxin, quinidine, and nitroglycerin.
- Daily use of:
- Opiate-containing medications for chronic pain.
- Inhaled corticosteroids.
- Subjects will be instructed to refrain from using any study-prohibited drugs/medications (both recreational and prescription) throughout their participation in the study. After final eligibility is confirmed, subjects who report taking contraindicated medication(s) over the course of the study period may only remain eligible if the Study Physician and Principal Investigator determine that the contraindicated medication(s) do/did not significantly impact the study design, data quality, and/or subject safety and welfare. Subjects are permitted to take necessary prescription medications not included within the exclusion list during the study.
- General Exclusion
- Past, current, anticipated, or pending enrollment in another research program over the study period that could potentially impact subject safety, study data, and/or the study design as determined by the Principal Investigator and/or Study Physician.
- Participation in a dietary program within the past 30 days.
- Any medical condition, illness, disorder, adverse event (AE), or concomitant medication that could compromise participant safety or significantly impact study performance as determined by the Principal Investigator and/or Study Physician. Subjects may be deemed ineligible for any of the aforementioned reasons at any point throughout the study, as well as during the initial telephone screen.
- Significant non-compliance with protocol and/or study design as determined by the Principal Investigator and/or Study Physician. Subjects may be deemed ineligible at any point throughout the study.
- Low or borderline intellectual functioning - determined by receiving a score of less than 85 on the Shipley Institute of Living Scale (SILS), which correlates with the Wechsler Adult Intelligence Scale-Revised (WAIS-R) Estimated IQ Test.
- fMRI Exclusion Criteria
- History of claustrophobia.
- Being left-handed.
- Lifetime history of stroke.
- Having a cochlear implant or wearing bilateral hearing aids.
- History of notable head trauma. Although notable head trauma is typically defined as being knocked unconscious for a period of three minutes or longer, notable head trauma will be evaluated on a case-by-case basis by the appropriate personnel prior to an eligibility decision, considering exceptions can be made based on the nature and severity of the trauma.
- History of brain or spinal tumor.
- Pacemakers, certain metallic implants or objects, or presence of metal in the eye as contraindicated for MRI.
- Any circumstances (e.g., exclusionary metal implants, certain dental work, and/or physical impairments) and/or conditions that may interfere with MRI and MRI-related study visit procedures. All potential exclusionary circumstances and/or conditions will be evaluated on a case-by-case basis by the appropriate personnel prior to an eligibility decision.
- History of gunshot wounds. Injuries from BB guns will be evaluated on a case-by-case basis by the appropriate personnel prior to an eligibility decision.
- History of epilepsy and/or recurrent or uncontrolled seizures.
- Weight greater than 250 lbs at Intake Visit or self-reported at phone screen. If a participant weighs less than or equal to 250 lbs at Intake, but presents with a weight greater than 250 lbs at either Scan 1 and/or Scan 2, the participant may be permitted to proceed with the scan as long as the participant's weight does not exceed 300 lbs.
- A positive urine drug screen (UDS) for cocaine, opiates, amphetamines, methamphetamines, phencyclidine (PCP), ecstasy (MDMA), barbiturates, benzodiazepines, methadone, and/or oxycodone at intake or either Scan Visit.
- A BrAC greater than 0.000 at intake or either Scan Visit.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
The purpose of this research study is to better understand why people gain weight when they quit smoking by examining food intake and changes in brain activity in smokers when they are smoking as usual compared to when they have been deprived of cigarettes (i.e., have not smoked for 4 days) as compared to a non-smoker control group.
Read the detailed description
Tobacco use and obesity are the two leading causes of preventable deaths. Because these two behaviors share common brain reward mechanisms, reducing one behavior often leads to increases in the other behavior. Behavioral Economic and Incentive Salience models shed much light on this clinical problem. Smoking cessation produces reward dysregulation that can alter the motivational salience of other reinforcers, particularly food. After stopping smoking, smokers increase between-meal snacking, especially foods high in fat and sugar. Increases in caloric intake occur within days of quitting smoking, and are clinically significant. The investigators have also shown that smoking cessation produces working memory deficits and reduces activity in the brain's cognitive control circuits, making it even more difficult to exert self-control over temptations to eat highly rewarding foods. Thus, smokers have a double challenge: food becomes more salient and reinforcing at a time when their neurocognitive resources are compromised.
Neuroimaging can identify mechanisms underlying behavior change beyond self-report and behavioral measures. The proposed functional magnetic resonance imaging (fMRI) study breaks new ground by integrating concepts and tools from the fields of behavioral economics and cognitive neuroscience to accelerate the study of mechanisms underlying PCWG. The investigators will use a previously validated within-subject crossover neuroimaging study design to examine changes in working memory, food salience (cue-induced craving), and food reinforcement processes in the brain after 4 days of smoking cessation (vs. smoking as usual). A non-smoker control group will provide insight into baseline differences from smokers (abstinent and satiated). Caloric intake, the primary outcome, will be assessed using 24-hr. food recalls during each study period. The investigators will assess three parallel pathways including: working memory, food cue reactivity, and food reinforcement at the neural and behavioral levels.
This study will provide new insights about how the brain can constrain or promote the ability of smokers to prevent post cessation weight gain (PCWG) and lead to new interventions that integrate neural and behavioral framework. Support for our predictions would inform testing of novel approaches to prevent PCWG, such as computerized neurocognitive exercise training to increase DLPFC activity and shift activity away from reward sensitive brain networks.
- Conditions
- Nicotine Use Disorder
- Being tested
- Practice Quit Attempt
- Keywords
- Nicotine Addiction, Quitting Smoking
- Medical subject headings
- Tobacco Use Disorder, Smoking Cessation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Practice Quit AttemptOther
Smokers will be studied under 2 conditions: smoking as usual and during a 4 day practice quit attempt.
| Study group | Role | What they receive |
|---|---|---|
| Smoker Group | Experimental | The smokers group will be scanned on 2 occasions: (1) after a 4 day monitored practice quit attempt (biochemically verified), and (2) after 4 days of smoking as usual (order counterbalanced). Receives: Other: Practice Quit Attempt |
| Non-Smoking Comparison Group | No intervention | Healthy non-smokers will complete one period (comparable to abstinence arm) of the study to serve as a baseline comparison group. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Abstinence Induced Change in Task BOLD Signal Change
The primary outcome measure is change in BOLD signal for the Food Cue-Induced Craving primary regions of interest for the BOLD fMRI analysis are anterior cingulate gyrus (ACC), Insula, Ventral Striatum (VS), and orbital frontal cortex (OFC). For the Working Memory N-Back Task the primary regions of interest for the BOLD analysis will be dorsal lateral prefrontal cortex (DLPFC) and posterior cingulate gyrus (PCC).
Measured: BOLD fMRI is collected on days 4 and 32 of protocol
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2018
- Study start1 Mar 2018
- Primary completion1 Apr 2023
- Study completion30 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Nicotine Use DisorderStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- This is a within-subject cross-over neuroimaging investigation of 3 potential neural mechanisms of increased caloric intake during initial smoking cessation. Eighty smokers will be scanned on 2 occasions: (1) after 4 days of monitored abstinence (biochemically verified), and (2) after 4 days of smoking as usual (order counterbalanced). In addition, 30 healthy non-smokers (matched for sex, age, and education) will complete one period of the study to serve as a baseline comparison group.
- Masking
- None (open label)
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, James Loughead, University of Pennsylvania
- Investigators
- James Loughead, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03438188
- Sponsor's protocol ID
- 828958
- Acronym
- SIT
- Status last verified
- Jan 2025
- First submitted
- 9 Feb 2018
- Last updated
- 5 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neural Basis of Eating Behavior in Abstinent Smokers
- ClinicalTrials.gov ID
- NCT03438188
- Acronym / sponsor ID
- SIT / 828958
- Conditions
- Nicotine Use Disorder
- Keywords
- Nicotine Addiction, Quitting Smoking
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 1 Mar 2018 (actual)
- Primary completion
- 1 Apr 2023 (actual)
- Study completion
- 30 Aug 2023 (actual)
- First posted
- 19 Feb 2018 (actual)
- Results
- Posted 5 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to better understand why people gain weight when they quit smoking by examining food intake and changes in brain activity in smokers when they are smoking as usual compared to when they have been deprived of cigarettes (i.e., have not smoked for 4 days) as compared to a non-smoker control group.
Detailed description
Tobacco use and obesity are the two leading causes of preventable deaths. Because these two behaviors share common brain reward mechanisms, reducing one behavior often leads to increases in the other behavior. Behavioral Economic and Incentive Salience models shed much light on this clinical problem. Smoking cessation produces reward dysregulation that can alter the motivational salience of other reinforcers, particularly food. After stopping smoking, smokers increase between-meal snacking, especially foods high in fat and sugar. Increases in caloric intake occur within days of quitting smoking, and are clinically significant. The investigators have also shown that smoking cessation produces working memory deficits and reduces activity in the brain's cognitive control circuits, making it even more difficult to exert self-control over temptations to eat highly rewarding foods. Thus, smokers have a double challenge: food becomes more salient and reinforcing at a time when their neurocognitive resources are compromised.
Neuroimaging can identify mechanisms underlying behavior change beyond self-report and behavioral measures. The proposed functional magnetic resonance imaging (fMRI) study breaks new ground by integrating concepts and tools from the fields of behavioral economics and cognitive neuroscience to accelerate the study of mechanisms underlying PCWG. The investigators will use a previously validated within-subject crossover neuroimaging study design to examine changes in working memory, food salience (cue-induced craving), and food reinforcement processes in the brain after 4 days of smoking cessation (vs. smoking as usual). A non-smoker control group will provide insight into baseline differences from smokers (abstinent and satiated). Caloric intake, the primary outcome, will be assessed using 24-hr. food recalls during each study period. The investigators will assess three parallel pathways including: working memory, food cue reactivity, and food reinforcement at the neural and behavioral levels.
This study will provide new insights about how the brain can constrain or promote the ability of smokers to prevent post cessation weight gain (PCWG) and lead to new interventions that integrate neural and behavioral framework. Support for our predictions would inform testing of novel approaches to prevent PCWG, such as computerized neurocognitive exercise training to increase DLPFC activity and shift activity away from reward sensitive brain networks.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a within-subject cross-over neuroimaging investigation of 3 potential neural mechanisms of increased caloric intake during initial smoking cessation. Eighty smokers will be scanned on 2 occasions: (1) after 4 days of monitored abstinence (biochemically verified), and (2) after 4 days of smoking as usual (order counterbalanced). In addition, 30 healthy non-smokers (matched for sex, age, and education) will complete one period of the study to serve as a baseline comparison group.
| Arm | Type | Receives |
|---|---|---|
| Smoker Group | Experimental | Other: Practice Quit AttemptThe smokers group will be scanned on 2 occasions: (1) after a 4 day monitored practice quit attempt (biochemically verified), and (2) after 4 days of smoking as usual (order counterbalanced). |
| Non-Smoking Comparison Group | No intervention | –Healthy non-smokers will complete one period (comparable to abstinence arm) of the study to serve as a baseline comparison group. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Male and female participants who are between 18 and 45 years of age.
- Smoking group - 80 treatment-seeking smokers who self-report smoking at least 10 cigarettes (menthol and/or non-menthol) per day for at least the last 6 months. Smoking status will be confirmed by CO greater than or equal to 8 parts per million (ppm) at the Intake Visit.
- Non-smoking group - 30 individuals reporting fewer than 100 lifetime cigarettes and not even a puff of a cigarette for a minimum of 2 years. Smoking status of non-smokers will be confirmed by CO less than 5ppm. They will be matched to the smoker group on age, sex, and education.
- Plan to live in the area for the duration of the study (i.e. ~8 weeks/2 months).
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the combined consent and HIPAA form.
Key exclusion criteria (66 listed)
- Subjects who present and/or self-report with the following criteria will not be eligible to participate in the study:
- Smoking Behavior
- Regular use of nicotine-containing products other than cigarettes (e.g. chewing tobacco, snuff, snus, cigars, e-cigs, etc.). Participants agreeing to abstain from using nicotine- containing products other than cigarettes will be considered eligible.
- Current enrollment or plans to enroll in another research and/or smoking cessation program over the duration of the study (i.e. ~8 weeks/2 months).
- Anticipated use (within the next ~8 weeks/2 months) of any nicotine substitutes and/or smoking cessation treatments/medications unless provided through the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Practice Quit AttemptSmokers will be studied under 2 conditions: smoking as usual and during a 4 day practice quit attempt. | Other | Smoker Group |
Primary outcome
Abstinence Induced Change in Task BOLD Signal Change
Time frame: BOLD fMRI is collected on days 4 and 32 of protocol
The primary outcome measure is change in BOLD signal for the Food Cue-Induced Craving primary regions of interest for the BOLD fMRI analysis are anterior cingulate gyrus (ACC), Insula, Ventral Striatum (VS), and orbital frontal cortex (OFC). For the Working Memory N-Back Task the primary regions of interest for the BOLD analysis will be dorsal lateral prefrontal cortex (DLPFC) and posterior cingulate gyrus (PCC).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Loughead principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Practice Quit Attempt in people with Nicotine Use Disorder, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 66 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Abstinence Induced Change in Task BOLD Signal Change (time frame: BOLD fMRI is collected on days 4 and 32 of protocol). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2025.