- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03204396
Smoking Cessation Facilitated by Glucagon-like Peptide-1 (GLP-1) Analogues (SKIP)
Smoking Cessation Facilitated by Glucagon-like Peptide-1 (GLP-1) Analogues - a Randomized, Double-blind, Placebo-controlled Trial
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.
Study Overview
Status
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Basel, Switzerland, 4031
- Universitätsspital Basel
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Active Comparator: Intervention group
Dulaglutide (Trulicity®) 1.5 mg in 0.5 ml, via pen s.c.
once weekly for 12 weeks.
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Application of Dulaglutide (Trulicity®) 1.5 mg s.c.
once weekly for 12 weeks.
Other Names:
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Placebo Comparator: Placebo group
0.5 ml normal saline (0.9% sodium chloride (NaCl)), injection s.c.
via syringe once weekly for 12 weeks.
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Application of 0.5 ml normal saline (0.9% sodium chloride [0.9% NaCl]) once weekly for 12 weeks
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Point prevalence abstinence rate at week 12
Time Frame: 12 weeks
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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
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12 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Body weight
Time Frame: 12 weeks
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Change in body weight in kg (and BMI [kg/m²]) relative to baseline at week 12 of dulaglutide treatment versus placebo.
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12 weeks
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Point prevalence abstinence rate at week 24 and 52
Time Frame: 52 weeks
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Point prevalence abstinence rate at weeks 24 and 52 of dulaglutide treatment and SOC versus SOC alone, confirmed with end-expiratory exhaled carbon monoxide measurements of 10 ppm or less
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52 weeks
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Prolonged abstinence rate at week 24 and 52
Time Frame: 52 weeks
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52 weeks
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Smoking reduction at week 12, 24, and 52
Time Frame: 52 weeks
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52 weeks
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Change of craving at week 4 and 12 relative to baseline
Time Frame: 12 weeks
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12 weeks
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Change of body weight in kg (and BMI [kg/m²]) at week 4, 8, 24, and 52
Time Frame: 52 weeks
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52 weeks
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Change in haemoglobin A1c levels at week 12, 24, and 52
Time Frame: 52 weeks
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52 weeks
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Craving measured by a Visual Analogue Scale (VAS) in the substudy "fMRI"
Time Frame: at week 12
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Behavioural endpoint of the substudy fMRI.
The VAS rating scale includes seven steps from no craving to high craving.
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at week 12
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Working memory performance investigated by the N-back task score in the substudy "fMRI"
Time Frame: at week 12
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Behavioural endpoint of the substudy fMRI.
During the N-back task, all subjects see series of letters with an interstimulus interval of 2 s.
Each stimulus is presented for 1 s.
During a baseline (0-back) condition, subjects are required to press the button with the right hand when the letter "X" appears.
During 1-back and 2-back conditions, participants are instructed to press the button if the currently presented letter is the same as that presented 1 (1-back condition) or 2 trials beforehand (2-back condition).
The three conditions will be presented in ten alternating 30 s blocks (2 × 1-back, 3 × 2-back and 5 × 0-back) matched for the number of target letters per block (i.e., 2 or 3), in a pseudo-random order.
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at week 12
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Blood oxygenated level dependent (BOLD) signal in fMRI in the substudy "fMRI"
Time Frame: at week 12
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Functional neuronal changes are assessed through the surrogate of blood oxygenated level dependent (BOLD) signal, an indirect measure of neural activity.
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at week 12
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Change in structural plasticity of grey and white matter in fMRI in the substudy "fMRI"
Time Frame: at week 0 and at week 12
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Change in structural plasticity of grey and white matter in regions parts of the reward pathway (i.e.
anterior cingulate cortex, insula, striatum) and in subcortical regions.
One T1 sequence and one DTI sequence will be performed to investigate changes in grey and white matter.
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at week 0 and at week 12
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Change of resting energy expenditure (REE) in the substudy "Energy"
Time Frame: at week 0 and at week 12
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Kcal per 24 hours.
It is assessed by indirect calorimetry measuring volume of oxygen uptake (VO2) and expelled volume of carbon dioxide (VO2) in ml/min and calculated by the Weir Equation REE = [3.9
* (VO2) + 1.1 (VCO2)] * 1.44.
The respiratory quotient (RQ) is calculated by dividing VCO2 by VO2.
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at week 0 and at week 12
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Change in body composition in the substudy "Energy"
Time Frame: at week 0 and at week 12
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Body composition is assessed by bioelectrical impedance analysis.
Measures are muscle and fat mass as a proportion (%) of total body weight.
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at week 0 and at week 12
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Change in haemodynamic parameters in the substudy "Energy"
Time Frame: at week 0, 12, 24, 52
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Blood pressure (mmHg), heart rate (beats per minute), cardiac index (l/min/m2), and peripheral vascular resistance (Pa*[s/m3]) assessed by non-invasive thoracic bioimpedance (HOTMAN®)
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at week 0, 12, 24, 52
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Change in sympathetic activity in the substudy "Energy"
Time Frame: at week 0 and at week 12
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Plasma catecholamine (epinephrine and norepinephrine) and neuropeptide Y (NPY)* levels measured in pg/ml.
NPY is a 36 aminoacid peptide well known to potentiate the action of catecholamine postsynaptically through the Y1 receptor and inhibit presynaptically the catecholamine secretion through the Y2 receptor
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at week 0 and at week 12
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Collaborators and Investigators
Investigators
- Principal Investigator: Bettina Winzeler, Dr., University Hospital Basel, Endokrinology, diabetology, metabolism
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2017-00286
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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