Smoking Cessation Facilitated by Glucagon-like Peptide-1 (GLP-1) Analogues

Study Overview
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Brief Summary
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Cigarette smoking is the leading preventable cause of premature death worldwide. However smoking is a very difficult addiction to break whereby main reasons for not quitting or relapsing after cessation are the nicotine withdrawal syndrome and post-cessational weight gain. GLP-1 analogues are well known to stimulate insulin secretion and to reduce energy intake and therefore body weight. Recent findings from animal and human studies suggest a role of GLP-1 in the pathophysiology of addiction. The putative role of GLP-1 analogues in nicotine reward regulation combined with its weight reducing effects might be of major interest in view of novel pharmacotherapeutic options for smoking cessation. Substudy fMRI: This substudy is to evaluate effects of Dulaglutide treatment on functional neuronal changes in smokers who want to quit smoking. Substudy Energy: This substudy is to investigate the effect of Dulaglutide (Trulicity®) on REE and further parameters associated with energy metabolism (bodycomposition, haemodynamic parameters and catecholamine action) in a subset of patients recruited for the main trial.

Detailed Description
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Cigarette smoking is the leading preventable cause of premature death worldwide. However smoking is a very difficult addiction to break and despite established smoking cessation programs quit rates are low, especially in the real-life setting. The main reasons for not quitting or relapsing after cessation are the nicotine withdrawal syndrome and post-cessational weight gain. GLP-1 analogues are well known to stimulate insulin secretion and to reduce energy intake and therefore body weight. Recent findings from animal and human studies suggest a role of GLP-1 in the pathophysiology of addiction. The putative role of GLP-1 analogues in nicotine reward regulation combined with its weight reducing effects might be of major interest in view of novel pharmacotherapeutic options for smoking cessation. Substudy fMRI (60 patients): Supposing that GLP-1 and analogues modulates nicotine induces reward system this substudy is to analyze if treatment with Dulaglutide (Trulicity®) attenuates craving and therefore functional brain activation. It is to evaluate effects of Dulaglutide treatment on functional neuronal changes in smokers who want to quit smoking. Substudy Energy (60 patients): The aim of the substudy Energy is to investigate the effect of Dulaglutide (Trulicity®) on REE and further parameters associated with energy metabolism (bodycomposition, haemodynamic parameters and catecholamine action) in a subset of patients recruited for the main trial.

Official Title
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Smoking Cessation Facilitated by Glucagon-like Peptide-1 (GLP-1) Analogues - a Randomized, Double-blind, Placebo-controlled Trial

Conditions
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Craving, Glucagon-like Peptide-1, Smoking Cessation, Weight Change, Body

Intervention / Treatment
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* Drug: Dulaglutide
* Drug: 0.5 ml normal saline (0.9% sodium chloride [0.9% NaCl])


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for the main study: Age 18 to 75 years Daily smokers who are willing to quit and exhibit one of the following criteria: ≥10 cigarettes per day or At least moderate nicotine dependence defined by a Fagerstroem Score of ≥5 Points or Tobacco associated disease Treatment with varenicline (Champix®) Additional Inclusion Criteria for the substudy fMRI: Only patients aged 18-50 years are eligible Additional Inclusion Criteria for the substudy Energy: BMI of 18-30 kg/m2 Exclusion Criteria for the main study: Pregnancy (incl. wish to become pregnant within next 3 months) or breast feeding Pre-existing Treatment with GLP-1 agonists History of pancreatitis Severe renal insufficiency (estimated glomerular Filtration rate smaller than 30 ml/min/1.73 m2) Instable psychiatric conditions Anorexia nervosa Additional Exclusion Criteria for the substudy fMRI: Medical conditions that affect brain function (e.g. stroke, epilepsy, space occupying lesions, multiple sclerosis, Parkinson's disease, dementia, transient ischemic attack), Current use of medications that alter brain function Current illicit drug abuse including marijuana (alcohol ≤ 1 drink per day allowed) Claustrophobia, cardiac pacemaker, electronic device or ferromagnetic metal foreign bodies

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomized, double-blind, placebo-controlled trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention group<br>Dulaglutide (Trulicity®) 1.5 mg in 0.5 ml, via pen s.c. once weekly for 12 weeks. | Drug: Dulaglutide<br>* Application of Dulaglutide (Trulicity®) 1.5 mg s.c. once weekly for 12 weeks.<br>* Other names: Trulicity;|
| Placebo Comparator: Placebo group<br>0.5 ml normal saline (0.9% sodium chloride (NaCl)), injection s.c. via syringe once weekly for 12 weeks. | Drug: 0.5 ml normal saline (0.9% sodium chloride [0.9% NaCl])<br>* Application of 0.5 ml normal saline (0.9% sodium chloride [0.9% NaCl]) once weekly for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Point prevalence abstinence rate at week 12 | Point prevalence abstinence rate at week 12 of dulaglutide treatment and Standard of care (SOC) versus SOC alone, confirmed with end-expiratory exhaled carbon monoxide measurements of 10 ppm or less | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Body weight | Change in body weight in kg (and BMI [kg/m²]) relative to baseline at week 12 of dulaglutide treatment versus placebo. | 12 weeks |