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Daily Liraglutide for Nicotine Dependence (DAL)

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ClinicalTrials.gov Identifier: NCT03712098
Recruitment Status : Recruiting
First Posted : October 19, 2018
Last Update Posted : June 5, 2019
Sponsor:
Collaborator:
Novo Nordisk A/S
Information provided by (Responsible Party):
Rebecca Ashare, University of Pennsylvania

Brief 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.

Condition or disease Intervention/treatment Phase
Smoking Cessation Weight, Body Drug: Liraglutide Drug: Placebo Behavioral: Smoking Cessation Counseling Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
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)
Primary Purpose: Treatment
Official Title: Glucagon-like Peptide-1 Receptor Agonists as Novel Pharmacotherapies for Nicotine Dependence
Actual Study Start Date : November 29, 2018
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : May 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Liraglutide

Arm Intervention/treatment
Experimental: Smoking Cessation Counseling & Liraglutide
Participants receive 8 sessions of smoking cessation behavioral counseling and 32 weeks of the medication liraglutide. Liraglutide comes in a pre-filled pen and is self-injected one time per day into the abdomen, thigh, or upper arm area. The dosing regimen, which follows FDA guidelines and is documented to be safe and well-tolerated in prior clinical studies, will begin at 0.6 mg and increase weekly by 0.6 mg until the recommended dose of 3 mg is reached (Weeks 1 through 5) and will continue at the 3 mg dose through the end of the study (Week 32).
Drug: Liraglutide
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.
Other Name: Saxenda

Behavioral: Smoking Cessation Counseling
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.

Active Comparator: Smoking Cessation Counseling & Placebo
Participants receive 8 sessions of smoking cessation behavioral counseling and 32 weeks of placebo. The placebo comes in a pre-filled pen and is self-injected one time per day into the abdomen, thigh, or upper arm area. The dosing regimen, which is the same as the liraglutide regimen, will begin at 0.6 mg and increase weekly by 0.6 mg until 3 mg is reached (Weeks 1 through 5) and will continue at the 3 mg dose through the end of the study (Week 32).
Drug: Placebo
The placebo is an inactive substance that is designed to look like liraglutide but contains no medication.

Behavioral: Smoking Cessation Counseling
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.




Primary Outcome Measures :
  1. 7-day point prevalence smoking abstinence at 12 weeks post-Target Quit Date [ Time Frame: Week 18 ]
    Biochemically verified carbon monoxide (CO) reading <5 using a Vitalograph Breath CO Analyzer

  2. 7-day point prevalence smoking abstinence at 26 weeks post-Target Quit Date [ Time Frame: Week 32 ]
    Biochemically verified carbon monoxide (CO) reading <5 using a Vitalograph Breath CO Analyzer


Secondary Outcome Measures :
  1. Body weight at 12 weeks post-Target Quit Date [ Time Frame: Week 18 ]
    Body weight will be measured by digital scale (pounds, ounces) wearing light clothing without shoes

  2. Body weight at 26 weeks post-Target Quit Date [ Time Frame: Week 32 ]
    Body weight will be measured by digital scale (pounds, ounces) wearing light clothing without shoes


Other Outcome Measures:
  1. Calories consumed per day [ Time Frame: Weeks 0, 5, 18, & 32 ]
    The research team staff will use a multi-pass method with an interactive computerized software program, the ASA24® (Automated Self-Administered 24-hour Recall), to determine total kcal/day with participants over the phone.

  2. Relative reinforcing value of food (RRVF) during acute nicotine withdrawal [ Time Frame: Week 0 & Week 5 ]
    Participants choose between a standard low effort monetary reward and either (on separate trials) a food or monetary reward of higher value and effort. Each trial presents a choice between a standard reward (27 button clicks for $0.25) or exerting greater effort to earn a larger reward. On half of the trials, larger rewards will be $0.50 (2 x standard value). In the remaining trials the larger reward will be double the calibrated snack portion (e.g., 20 M&Ms). Effort for more valuable rewards will vary from 27 to 775 responses in 25 log10 steps. Pairs of visual stimuli depicting the two options appear for 4.5 sec followed by a 3-14 sec inter-trial interval.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. 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. Providing a breath alcohol concentration (BrAC) reading greater than 0.00.
  4. A positive urine drug screen for cocaine, methamphetamines, PCP, barbiturates, and/or ecstasy (MDMA).

    1. Those who screen positive for amphetamines, benzodiazepines, methadone, oxycodone, and/or and opiates (low level cut-off 300 ng/mL) and who are prescribed these medications will be reviewed on a case-by-case basis by the PI and Study Physician. 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 study visit.
  2. Current diagnosis of unstable and untreated major depression, as determined by self-report & 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 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. Known or suspected allergy to liraglutide, excipients, or related products. * Participants presenting with SBP greater than 159 mmHg and/or 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).

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03712098


Contacts
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Contact: Molly R Ruben, MPH 215-746-8420 Molly.Ruben@pennmedicine.upenn.edu

Locations
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United States, Pennsylvania
Center for Interdisciplinary Research on Nicotine Addiction, University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Molly R Ruben, MPH    215-746-8420    Molly.Ruben@pennmedicine.upenn.edu   
Sponsors and Collaborators
Rebecca Ashare
Novo Nordisk A/S
Investigators
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Principal Investigator: Rebecca L Ashare, PhD University of Pennsylvania

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Responsible Party: Rebecca Ashare, Assistant Professor, Department of Psychiatry, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT03712098     History of Changes
Other Study ID Numbers: 831835
First Posted: October 19, 2018    Key Record Dates
Last Update Posted: June 5, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Body Weight
Tobacco Use Disorder
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Signs and Symptoms
Liraglutide
Nicotine
Glucagon-Like Peptide 1
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists