{
  "abstract": "Background\n\nSmoking remains the leading preventable cause of cancer mortality in the United States. Varenicline is the most effective monotherapy for smoking cessation, and combining it with nicotine replacement therapy (NRT) may further improve cessation rates. Smartphone-based medication adherence interventions could enhance pharmacotherapy adherence and cessation outcomes.Objective\n\nThis trial will evaluate the efficacy of varenicline plus nicotine lozenges and a smartphone adherence intervention for promoting smoking cessation.Methods\n\nThis fully remote, 2 × 2 factorial randomized controlled trial will enroll 496 adults from Oklahoma who smoke cigarettes daily. Participants will be randomized to 1 of 4 conditions: (1) varenicline (VAR) + nicotine lozenges (NRT) versus VAR alone and (2) a smartphone-based smoking cessation app with adherence components (COMBO-A [adherence]) or without adherence components (COMBO-B [basic]). The primary outcomes are biochemically verified 7-day point prevalence abstinence at 26 weeks post quit date and medication adherence during the treatment period. Secondary outcomes include withdrawal symptoms and medication side effects over the 12-week treatment period.Results\n\nStudy recruitment began in July 2026. As of the date of this paper's submission, 8 participants have been enrolled. Enrollment is expected to be completed by December 2028, with primary data collection and follow-up completed by June 2029. Primary study results are anticipated later in 2029.Conclusions\n\nIf effective, VAR+NRT would offer a new evidence-based cessation treatment option. If the smartphone adherence intervention improves medication adherence and cessation, it could be adapted for other pharmacotherapies and widely implemented. Ultimately, this research aims to enhance cessation efforts and reduce cancer risk among adults who smoke.",
  "abstract_shown": true,
  "affiliations": [
    "TSET Health Promotion Research Center, Stephenson Cancer Center, University of Oklahoma Health Campus, 655 Research Parkway, Oklahoma City, OK, 73104, United States, 1 (405) 271-6872.",
    "Department of Internal Medicine, University of Oklahoma Health Campus, Tulsa, OK, United States.",
    "Department of Behavioral and Social Sciences and Center for Alcohol and Addiction Studies, Brown University School of Public Health, Providence, RI, United States.",
    "Department of Medicine, Alpert Medical School, Brown University, Providence, RI, United States.",
    "Department of Family and Preventive Medicine, University of Oklahoma Health Campus, Oklahoma City, OK, United States.",
    "Department of Biostatistics and Epidemiology, Hudson College of Public Health, University of Oklahoma Health Campus, Oklahoma City, OK, United States.",
    "Department of Psychiatry and Behavioral Sciences, University of Oklahoma Health Campus, Oklahoma City, OK, United States.",
    "College of Pharmacy, University of Oklahoma Health Campus, Oklahoma City, OK, United States."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Nathalia M Machado",
      "orcid": "0000-0001-6534-2157"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Jasjit S Ahluwalia",
      "orcid": "0000-0003-1756-3646"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Michael S Businelle",
      "orcid": "0000-0002-9038-2238"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Summer G Frank-Pearce",
      "orcid": "0000-0003-0779-4926"
    },
    {
      "affs": [
        6
      ],
      "name": "Irina Baranskaya",
      "orcid": "0000-0003-4555-3621"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Emily T Hébert",
      "orcid": "0000-0001-5922-164X"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Munjireen S Sifat",
      "orcid": "0000-0003-1377-8981"
    },
    {
      "affs": [
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      ],
      "name": "Shannon H Gwin",
      "orcid": "0000-0002-6760-7312"
    },
    {
      "affs": [
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      ],
      "name": "Roma Thakur",
      "orcid": "0009-0000-5528-5478"
    },
    {
      "affs": [
        0
      ],
      "name": "Sharon Glassman",
      "orcid": "0000-0002-2705-4581"
    },
    {
      "affs": [
        7
      ],
      "name": "Henry W Kinnard",
      "orcid": "0009-0006-5275-3858"
    },
    {
      "affs": [
        0
      ],
      "name": "Gaurav Kumar",
      "orcid": "0000-0001-6226-8107"
    },
    {
      "affs": [
        0
      ],
      "name": "Deeksha Gupta",
      "orcid": "0000-0001-5120-7659"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Darla E Kendzor",
      "orcid": "0000-0002-7273-1916"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bebjpx45fxpaw.bib",
  "cited_by": 0,
  "doi": "10.2196/108379",
  "fulltext_url": "https://europepmc.org/articles/PMC13727020",
  "id": "bebjpx45fxpaw",
  "issns": [
    "1929-0748"
  ],
  "landing_url": "https://europepmc.org/article/MED/42970756",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Behavior Change"
    ],
    [
      "heading",
      "Engagement with and Adherence to Digital Health Interventions, Law of Attrition"
    ],
    [
      "heading",
      "Mobile Health (mhealth)"
    ],
    [
      "heading",
      "Protocol"
    ],
    [
      "heading",
      "RCTs - Protocols/Proposals (funded, already peer-reviewed, eHealth)"
    ],
    [
      "heading",
      "Substance Abuse"
    ],
    [
      "heading",
      "mHealth for Wellness, Behavior Change and Prevention"
    ],
    [
      "openalex",
      "2737|Smoking Behavior and Cessation"
    ]
  ],
  "openalex": "W7225074921",
  "pdf_url": "https://europepmc.org/articles/PMC13727020?pdf=render",
  "pmcid": "PMC13727020",
  "pmid": "42970756",
  "published": "2026-11-02",
  "publisher": "JMIR Publications Inc.",
  "ris": "https://research.draconitic.com/paper/bebjpx45fxpaw.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T15:20:43Z",
      "native_id": "MED:42970756",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42970756"
    },
    {
      "first_seen": "2026-11-05T12:23:14Z",
      "native_id": "PMC13727020",
      "source": "pmc",
      "url": "https://doi.org/10.2196/108379"
    }
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Smoking Behavior and Cessation",
      "subfield": "physiology"
    }
  ],
  "title": "A Randomized Factorial Trial of Varenicline, Nicotine Lozenges, and Smartphone Medication Adherence Reminders for Smoking Cessation: Protocol for the COMBO II Study.",
  "title_text": "A Randomized Factorial Trial of Varenicline, Nicotine Lozenges, and Smartphone Medication Adherence Reminders for Smoking Cessation: Protocol for the COMBO II Study.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:22:50Z",
  "url": "https://research.draconitic.com/paper/bebjpx45fxpaw",
  "venue": "JMIR research protocols",
  "versions": []
}