Clinical trial NCT03204396: Smoking Cessation Facilitated by Glucagon-like Peptide-1 (GLP-1) Analogues
Official title: Smoking Cessation Facilitated by Glucagon-like Peptide-1 (GLP-1) Analogues - a Randomized, Double-blind, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glucagon-like Peptide-1
Smoking Cessation
Weight Change, Body
Craving
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2017-07-02
Enrollment: 256
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized, double-blind, placebo-controlled trial
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Point prevalence abstinence rate at week 12
timeFrame: 12 weeks
Secondary outcomes:
measure: Change in Body weight
timeFrame: 12 weeks
Other outcomes:
measure: Point prevalence abstinence rate at week 24 and 52
timeFrame: 52 weeks
measure: Prolonged abstinence rate at week 24 and 52
timeFrame: 52 weeks
measure: Smoking reduction at week 12, 24, and 52
timeFrame: 52 weeks
measure: Change of craving at week 4 and 12 relative to baseline
timeFrame: 12 weeks
measure: Change of body weight in kg (and BMI [kg/m²]) at week 4, 8, 24, and 52
timeFrame: 52 weeks
measure: Change in haemoglobin A1c levels at week 12, 24, and 52
timeFrame: 52 weeks
measure: Craving measured by a Visual Analogue Scale (VAS) in the substudy "fMRI"
timeFrame: at week 12
measure: Working memory performance investigated by the N-back task score in the substudy "fMRI"
timeFrame: at week 12
measure: Blood oxygenated level dependent (BOLD) signal in fMRI in the substudy "fMRI"
timeFrame: at week 12
measure: Change in structural plasticity of grey and white matter in fMRI in the substudy "fMRI"
timeFrame: at week 0 and at week 12
measure: Change of resting energy expenditure (REE) in the substudy "Energy"
timeFrame: at week 0 and at week 12
measure: Change in body composition in the substudy "Energy"
timeFrame: at week 0 and at week 12
measure: Change in haemodynamic parameters in the substudy "Energy"
timeFrame: at week 0, 12, 24, 52
measure: Change in sympathetic activity in the substudy "Energy"
timeFrame: at week 0 and at week 12
Locations:
city: Basel
country: Switzerland
facility: Universitätsspital Basel
Study officials:
affiliation: University Hospital Basel, Endokrinology, diabetology, metabolism
name: Bettina Winzeler, Dr.
role: PRINCIPAL_INVESTIGATOR
References: