Daily Liraglutide for Nicotine Dependence
Condition: Smoking Cessation; Weight, Body
MeSH terms: Body Weight; Tobacco Use Disorder
Intervention: Liraglutide; Placebo; Smoking Cessation Counseling
Intervention description: Liraglutide 3.0 mg is an injectable medicine that may help some adults with excess weight (BMI ≥27) who also have weight-related medical problems or obesity (BMI ≥30) lose weight and keep the weight off. Liraglutide is approved by the U.S. Food and Drug Administration (FDA) for chronic weight management when combined with a reduced-calorie meal plan and physical activity.; The placebo is an inactive substance that is designed to look like liraglutide but contains no medication.; All participants receive manual-based counseling from a trained smoking cessation counselor. The counseling sessions are designed to enhance awareness of the harmful effects of smoking, assist the participant in developing skills to quit, and avoid relapse.
Intervention MeSH terms: Liraglutide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This is a randomized, double-blind, placebo-controlled, parallel arm pilot study with one between-subjects factor of medication group (liraglutide vs. placebo).
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This clinical research trial examines the effects of the GLP-1 receptor agonist liraglutide
      on smoking behavior, food intake, and weight gain. In this double-blind, placebo-controlled,
      parallel arm pilot study, overweight and obese smokers (N=40; 20 female and 20 male) will be
      randomized to 32 weeks of liraglutide or placebo and undergo 8 sessions of smoking cessation
      behavioral counseling. Outcomes are smoking abstinence and weight change.
    

Eligibility criteria:

        Inclusion Criteria:

        Eligible subjects will be males and females:

          1. 18 years of age or older who self-report smoking cigarettes (menthol and non-menthol)
             at least 10 times per day, on average, for the past 6 months.

          2. Interested in quitting smoking (defined as "intend to quit within one month").

          3. Body mass index (BMI) greater than or equal to 27 kg/m2 with one weight-related
             comorbidity (e.g. high blood pressure, high cholesterol, dyslipidemia) or greater than
             or equal to 30 kg/m2 per the manufacturer label for weight management.

          4. Women of childbearing potential (based on medical history) must consent to use a
             medically accepted method of birth control (e.g., condoms and spermicide, oral
             contraceptive, Depo-Provera injection, contraceptive patch, intrauterine device (IUD),
             tubal ligation) or agree to abstain from sexual intercourse during the time they are
             in the study.

          5. Able to communicate (speak, read, and write) fluently in English.

          6. Capable of giving written informed consent before any study-related activities, which
             includes compliance with the requirements and restrictions listed in the combined
             consent/HIPAA form.

          7. If current or past diagnosis of bipolar disorder, eligible if:

               1. No psychotic features

               2. MADRS: total score less than 8 (past 4 weeks); suicidal item score less than 1
                  (past 4 weeks)

               3. Young Mania Rating Scale (Y-MRS): total score less than 8 (past 4 weeks);
                  irritability, speech content, disruptive or aggressive behavior items score less
                  than 3 (past 4 weeks)

               4. No psychiatric hospitalization or Emergency Room visits for psychiatric issues in
                  the past 6 months

               5. No aggressive or violent acts or behavior in the past 6 months

        Exclusion Criteria:

        Subjects who present with and/or self-report the following criteria will not be eligible to
        participate in the study.

        Smoking Behavior:

          1. Current enrollment in a smoking cessation program, or use of other smoking cessation
             medications (e.g. Chantix/varenicline, Zyban/bupropion, nicotine replacement
             therapy/gum/patch, etc.) in the last month or plans to do either in the next 2 months.

          2. Daily use of chewing tobacco, snuff and/or snus, or electronic cigarettes.

        Alcohol/Drug Use:

          1. Self-report current alcohol consumption that exceeds 25 standard drinks/week over the
             past 6 months.

          2. Current untreated and unstable diagnosis of severe substance use disorder (eligible if
             past use and/or if receiving treatment and stable for at least 30 days). Current
             untreated and unstable moderate substance use disorder requires Study Physician
             approval.

          3. A positive urine drug screen for cocaine, methamphetamines, phencyclidine (PCP),
             barbiturates, and/or ecstasy (MDMA).

               1. Participants believed to have a false-positive result on the drug screen may
                  continue with the study with investigator approval.

        Medical:

          1. Females who self-report current pregnancy, planning a pregnancy during the study,
             currently breastfeeding/lactating, or not using adequate contraceptive measures. All
             female participants will undergo a urine pregnancy test at Intake and at every
             in-person study visit.

          2. Current diagnosis of unstable and untreated major depression, as determined by
             self-report & MINI International Neuropsychiatric Interview (MINI) (eligible if stable
             for at least 30 days).

          3. Current or past diagnosis of psychotic disorder, as determined by self-report or MINI.
             Mood Disorder with Psychotic Features determined by MINI requires PI approval for
             eligibility.

          4. Suicide risk on the Columbia Suicide Severity Rating Scale (C-SSRS) indicated by
             active suicidal ideation (within past 30 days), any suicidal attempt within the past 2
             years, or 2 or more lifetime suicidal attempts.

          5. Self-reported kidney and/or liver disease or transplant.

          6. Heart/Cardiovascular disease (e.g., angina, coronary heart disease, stroke, etc.) in
             the past 6 months.

          7. Type-1 or type-2 diabetes (previously diagnosed or indicated by HbA1c level of 6.5% or
             higher).

          8. Uncontrolled hypertension (BP systolic greater than 159 and/or diastolic greater than
             99)*.

          9. Personal or family history of medullary thyroid carcinoma (MTC).

         10. Personal or family history of Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

         11. History of pancreatitis.

         12. History of gallbladder disease.

         13. A blood glucose level less than 70 mg/dl at the Intake Visit.

         14. Prior history, or plans, of surgical intervention for weight loss.

         15. Hypersensitivity to liraglutide or any product components.

         16. Current diagnosis of hyperthyroidism or hypothyroidism (requires thyroid function test
             review by study physician (SP) to determine eligibility)

         17. Recent weight loss (more than or equal to 5% body weight) in the past 3 months

               -  Participants presenting with systolic blood pressure (SBP) greater than 159 mmHg
                  and/or diastolic blood pressure (DBP) greater than 99 mmHg at the Intake visit
                  will be instructed to sit quietly for 10 minutes. Then the participant will have
                  a second blood pressure reading taken after a 10 minute period. If, after the
                  second reading the SBP greater than 159 mmHg and the DBP greater than 99 mmHg,
                  the individual will be instructed to sit comfortably for 10 minutes and then have
                  a third blood pressure reading. If, after the third reading the SBP greater than
                  159 mmHg and the DBP greater than 99 mmHg, the individual will be ineligible to
                  participate.

        Medications:

        1. Current or recent use (last 14 days) of weight loss medication, and/or use of
        medications known to impact weight (e.g. corticosteroids, excluding inhaled).

        General Exclusion:

          1. Current, anticipated, or pending enrollment in another research program over the next
             2-3 months that could potentially affect subject safety and/or the study data/design
             as determined by the Principal Investigator and/or Study Physician.

          2. Not planning to live in the area for the next 9 months.

          3. Previous participation in this trial (i.e., previously randomized and started study
             medication).

          4. Any impairment (physical and/or neurological) including visual or other impairment
             preventing ability to complete study tasks.

          5. Inability to provide informed consent or complete any of the study tasks as determined
             by the Principal Investigator.