History of Changes for Study: NCT05530577

Effects of Semaglutide on Nicotine Intake

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Study Record Versions

Version	Submitted Date	Changes
1	September 1, 2022	None (earliest Version on record)
2	October 21, 2022	Recruitment Status, Study Status and Contacts/Locations
3	November 14, 2023	Study Status, Contacts/Locations and Eligibility

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	21-1548
Brief Title:	Effects of Semaglutide on Nicotine Intake
Official Title:	Effects of Semaglutide on Nicotine Intake and Smoking Lapse
Secondary IDs:	R21DA047663-02 [U.S. NIH Grant/Contract]

Study Status


Record Verification:	September 2022
Overall Status:	Not yet recruiting
Study Start:	September 2022
Primary Completion:	August 2023 [Anticipated]
Study Completion:	October 2023 [Anticipated]

First Submitted:	August 26, 2022
First Submitted that Met QC Criteria:	September 1, 2022
First Posted:	September 7, 2022 [Actual]

Last Update Submitted that Met QC Criteria:	September 1, 2022
Last Update Posted:	September 7, 2022 [Actual]

Sponsor/Collaborators


Sponsor:	University of North Carolina, Chapel Hill
Responsible Party:	Sponsor
Collaborators:	National Institute on Drug Abuse (NIDA)

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:	Yes

Study Description

Brief Summary:

Tobacco use remains the foremost cause of preventable deaths in the U.S. and worldwide. Advancing new smoking cessation therapies, including those targeting novel biological mechanisms, is a critical public health priority. Accumulating evidence from preclinical studies suggests that glucagon-like peptide-1 (GLP-1) receptor agonists reduce intake and/or reinstatement of addictive drugs, including nicotine. However, translational work is necessary to establish whether GLP-1 receptor agonists alter aspects of nicotine response and smoking behavior in smokers. Human laboratory studies play a pivotal role in drug development by providing a time- and cost-efficient means of validating preclinical findings, also providing an ideal platform for studying mechanisms of medication effects. This is an experimental investigation to examine the effects of an approved GLP-1 receptor agonist on nicotine intake and reinstatement. Dependent smokers will be enrolled in a double-blind, parallel-arm trial with laboratory endpoints. Laboratory procedures will include a validated procedure for measuring smoking lapse/reinstatement after overnight abstinence. This study will provide initial laboratory evidence for the potential efficacy of GLP-1 receptor agonists as adjunctive treatments for smoking cessation.

Detailed Description:

Conditions


Conditions:	Tobacco Use Disorder Nicotine Addiction
Keywords:

Study Design


Study Type:	Interventional
Primary Purpose:	Basic Science
Study Phase:	Phase 2
Interventional Study Model:	Parallel Assignment
	Randomized parallel group design.
Number of Arms:	2
Masking:	Triple (Participant, Investigator, Outcomes Assessor)
Allocation:	Randomized
Enrollment:	48 [Anticipated]

Arms and Interventions

Arms	Assigned Interventions
Experimental: Semaglutide Participants will receive semaglutide via subcutaneous injections at escalating doses (0.25mg to 1.0mg) over 9 weeks.	Drug: Semaglutide Semaglutide (subcutaneous)
Sham Comparator: Sham/Placebo Participants will receive sham subcutaneous injections over 9 weeks.	Drug: Sham/placebo Sham subcutaneous injection

Outcome Measures


Primary Outcome Measures:
1.	Change in Nicotine Self-Administration [ Time Frame: baseline (Week 0) to post-medication (Week 8) ] Number of cigarettes smoked during a laboratory smoking procedure
2.	Change in Nicotine Reinstatement Duration [ Time Frame: baseline (Week 0) to post-medication (Week 8) ] Duration (minutes) of resistance to smoking reinstatement during a laboratory lapse task
Secondary Outcome Measures:
1.	Change in Daily Cigarette Smoking [ Time Frame: baseline (Week 0) to study endpoint (Week 10) ] Number of cigarettes consumed per day during medication exposure
Other Outcome Measures:
1.	Change in Cigarette Craving [ Time Frame: baseline (Week 0) to post-medication (Week 8) ] Self-reported craving during a cue exposure task
2.	Change in Subjective Responses to Cigarette Smoking [ Time Frame: baseline (Week 0) to post-medication (Week 8) ] Self-reported responses to cigarette smoking during a laboratory smoking procedure The Cigarette Purchase Task is a 21-question self-reported measure to understand motivation for obtaining cigarettes which asks participants about the number of cigarettes they would purchase and smoke based on an increasing cigarette cost.
3.	Change in Body Weight [ Time Frame: baseline (Week 0) to study endpoint (Week 10) ] Body weight
4.	Change in HbA1c [ Time Frame: baseline (Week 0) to study endpoint (Week 10) ] Hemoglobin A1C (HbA1c)

Eligibility


Minimum Age:	21 Years
Maximum Age:	65 Years
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	Yes
Criteria:	Inclusion Criteria: Age 21-65 Smoking 5+ cigarettes per day (on average) over the past year, with no period of abstinence > 90 days Biochemical verification of smoking status, based on expired CO > 8 at baseline Baseline Fagerström (FTND) score of 5+ (indicating at least moderate nicotine dependence) Reporting long-term motivation to quit smoking (defined as interest in a quit attempt within the next 3-18 months) Willingness to take study medication and complete study procedures Willingness to complete lab sessions involving cigarette smoking Ability to communicate in English Exclusion Criteria: Regular use of electronic nicotine delivery systems (ENDS/vaping), cigars, chewing tobacco or snuff, based on at least weekly use in the past 30 days Past 30-day use of nicotine replacement therapies/products Reporting past 30-day use of illicit drugs other than cannabis at baseline, or having a positive toxicology screen for illicit drugs other than cannabis at baseline Current engagement in alcohol or smoking cessation treatments, or currently engaged in intentional efforts to quit alcohol use Past 30-day use of: Sincalide, Sulfonylureas, insulin and insulin products or other medications that may interact with semaglutide, or weight control medications Prior use of semaglutide or other GLP-1 agonists Known or suspected hypersensitivity to study medication or related products Lifetime diagnosis of severe mental illness (including schizophrenia and bipolar disorder) Meeting criteria for current alcohol use disorder (AUD) or other substance use disorder (with the exception of tobacco or mild cannabis use disorder) History of suicide attempt, or recent (past 30 day) suicidal ideation, or psychiatric hospitalization in the last 6 months Current significant medical or neurological illness (based on self-report or medical record) including severe hepatic impairment or cirrhosis, impaired renal function (eGFR <50ml/min), acute or chronic pancreatitis, gastroparesis, gallbladder disease or cholelithiasis, other severe gastrointestinal disease, heart failure, coronary artery disease, stroke, seizure disorder, or other medical condition that poses a risk for the medication or alcohol administration components of the study (as determined by the MD) A personal or family history of medullary thyroid cancer or multiple endocrine neoplasia 2A or 2B Calcitonin greater than or equal to 50 ng/L Uncontrolled thyroid disease TSH >6.0 mIU/L or <0.4 mIU/L at screening History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g., subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery) History of Type 1 or Type 2 diabetes, or HbA1c >6.5% measured at screening History of diabetic retinopathy, proliferative retinopathy, or maculopathy History of diabetic ketoacidosis History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and carcinoma in situ) Currently nursing, pregnant, anticipating pregnancy in the next 6 months, or not using a highly effective contraceptive method as judged by the MD, and defined as: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) intrauterine device intrauterine hormone-releasing system bilateral tubal occlusion vasectomized partner sexual abstinence Elevation of serum lipase, amylase, direct (conjugated) bilirubin, or alkaline phosphatase (ALP), ALT, or AST) more than 3X the upper limit of normal on baseline bloodwork Baseline body mass index (BMI) <25kg/m2 or >35kg/m2 Uncontrolled hypertension or systolic BP >180 mmHg and/or diastolic BP >105 mmHg, averaged from three measurements Plans for travel outside of the local area in the upcoming 12 weeks that would interfere with lab visits during the study period (or other logistic factors that would make it difficult to commit to entire duration of study)

Contacts/Locations


Central Contact Person:	Christian Hendershot, PhD Telephone: (919) 962-5565 Email: christian_hendershot@med.unc.edu
Central Contact Backup:	Margret Powell Email: margret_powell@med.unc.edu
Study Officials:	Christian Hendershot, PhD Principal Investigator University of North Carolina, Chapel Hill
Locations:	United States, North Carolina
	University of North Carolina Chapel Hill, North Carolina, United States, 27599

IPDSharing


Plan to Share IPD:	Yes IPD will be shared with other investigators upon reasonable request.
	Supporting Information: Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) Clinical Study Report (CSR) Analytic Code
	Time Frame: Data will become available following publication of study manuscripts and will be available indefinitely.
	Access Criteria: Reasonable request from qualified investigator.
	URL:

References


Citations:
Links:
Available IPD/Information: