Impact of Sweeteners on the Addictive Threshold of Nicotine

NCT07771725 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 20000434452U54DA036151-11
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

To determine if sucralose, an artificial sweetener, modulates nicotine threshold doses for discrimination, subjective-rewarding effects, and reinforcement in smokers with varying levels of dependence.

Conditions

Smoking ( Cigarette)

Outcome Measures

Primary Outcomes (2)

• Drug Discrimination Scale (DDS) score.

  This scale asks the participants to select if they received Drug A or B and how confident they are in their selection on a scale of 0 to 10. Higher scores indicate more confidence.

  OnTest Days 1, 2, 3 and 4

• Drug Effects Questionnaire (DEQ) pleasurable effects score

  The DEQ pleasurable effects consists of 11 questions with total score range from 0-100. Higher scores indicate more positive effects.

  OnTest Days 1, 2, 3 and 4

Secondary Outcomes (1)

• Minnesota Nicotine Withdrawal Scale score

  OnTest Days 1, 2, 3 and 4

Study Arms (4)

Nicotine

ACTIVE COMPARATOR

These test days will evaluate two nicotine doses (0.05 mg/pulse and 0.1 mg/pulse)

Drug: Nicotine 0.05 mg/pulse and 0.1 mg/pulse

saline

PLACEBO COMPARATOR

Saline (sugar water)

Drug: Saline Placebo (0.5mL injection)

sucralose

ACTIVE COMPARATOR

participants practice using the e-cigarette and sample the sweet (sucralose) and control (unsweetened) flavors

Dietary Supplement: sucralose

unsweetened flavor

PLACEBO COMPARATOR

participants practice using the e-cigarette and sample the sweet (sucralose) and control (unsweetened) flavors

Dietary Supplement: Sugar syrup (Placebo)

Interventions

Nicotine 0.05 mg/pulse and 0.1 mg/pulse DRUG

Nicotine will be used and compared to saline given by IV push by study physician

Nicotine

Saline Placebo (0.5mL injection) DRUG

Saline will be used compared to the low dose of Nicotine given by IV push by study physician

saline

sucralose DIETARY_SUPPLEMENT

sweet flavor (sucralose) compared to unsweetened flavor

sucralose

Sugar syrup (Placebo) DIETARY_SUPPLEMENT

Unsweetened flavor compared to the sweetened flavor sucralose.

unsweetened flavor

Eligibility Criteria

• Age: 21 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Smoking at least for one year and more frequently than once a week, smoking status confirmed with a semi-quantitative urine nicotine test. Smokers will be stratified by level of dependence, assessed with the FTND 29 low or no dependence ≤3 and moderate or high dependence ≥ 4.
• In good health as verified by medical history, screening examination, and screening laboratory tests.
• For women, report using acceptable birth control methods.

You may not qualify if:

• History of major medical or psychiatric disorders that the physician investigator deems as contraindicated for the participant to be in the study;
• regular current use of certain psychotropic medications (such as mood stabilizers, antipsychotics, or anxiolytics being prescribed to treat bipolar disorder, psychosis or anxiety spectrum disorders, respectively);
• current untreated alcohol or substance use disorder for any other recreational or prescription drugs other than nicotine;
• for women, pregnant as determined by pregnancy screening, or breastfeeding; and 5) seeking (or undergoing) treatment for tobacco dependence or smoking.

Sponsors & Collaborators

• Yale University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

VA Hospital

West Haven, Connecticut, 06516, United States

Location

MeSH Terms

Conditions

Cigarette Smoking

Interventions

Nicotine; Pulse; Injections; trichlorosucrose

Condition Hierarchy (Ancestors)

Tobacco Smoking; Smoking; Behavior; Tobacco Use

Intervention Hierarchy (Ancestors)

Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Hemodynamics; Cardiovascular Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Mehmet Sofuoglu, M.D., Ph.D.

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mehmet Sofuoglu, M.D., Ph.D.

CONTACT

203-932-5711; Mehmet.Sofuoglu@yale.edu

Stacy A Minnix, B.S.

CONTACT

203--932-5711

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2026
• First Posted: August 18, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: August 31, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)