Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
GLP-1 receptor agonist, Chronic obstructive pulmonary disease, FDG/PET-CT, inflammation, weightloss, quality of life
Brief summary
The study is a 44 weeks, prospective, randomized, placebo-controlled, double-blinded, parallel group two-center trial. Forty patients are recruited among the outpatients of the chronic obstructive pulmonary disease (COPD) clinic, Hospital of South West Jutland and Lillebælt Hospital according to the inclusion and exclusion criteria. The patients are randomized to receive liraglutide 3 mg per day (initial dose 0.6 mg, increasing by 0.6 mg weekly until 3 mg is reached) or placebo. At baseline, after four weeks (assessment of the acute effect of liraglutide), 20 weeks, and 40 weeks (assessment of the combined effect of liraglutide and weight loss) and at week 44 (assessment of the weight-loss after discontinuation of liraglutide) the patients are assessed by physical examination, carbon monoxide (CO) diffusion test, pulmonary function test, biomarkers of inflammation (CRP, interleucine-6 (IL-6), monocyte chemitactic protein-1 (MCP-1)), Fluorodeoxyglucose (FDG)/PET-CT scan of the lungs, 6-minute walking test, respiratory polygraphy and validated questionnaires including basic dyspnea index, transition dyspnea index, COPD Assessment Test (CAT)-score, short-form-36 (SF-36) and Epworth Sleepiness Score.
Detailed description
COPD is a common disease characterized by pulmonary inflammation, reduced pulmonary capacity, reduced physical activity and quality of life. Obesity is likewise a common disease characterized by inflammation, reduced physical activity and quality of life. Targeting both obesity and inflammation may turn out beneficial for patients with COPD and obesity, and this study explore the possibility to reverse a vicious cycle of COPD, lack of physical activity and obesity. The primary objective of the study is to evaluate the effect of Liraglutide 3mg in patients with COPD on patient reported outcomes as measured by the Transition Dyspnea Index. The hypothesis is that Liraglutide 3mg exerts beneficial effects on measures of pulmonary function and quality of life in overweight patients with COPD by reducing body weight and reducing inflammatory activity.
Interventions
DRUGLiraglutide
Initially 0.6 mg daily, increasing weekly with 0.6 mg, until 3.0 mg is reached.
DRUGPlacebo
Matching injection
Sponsors
Claus Bogh Juhl
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
A prospective, randomized, placebo-controlled, double-blinded, parallel group and two-center trial.
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
1. Informed consent obtained before any trial-related activities 2. COPD as defined by FEV1/FVC\<70% after maximal broncho-dilatation and in accordance with the Gold guidelines 2017 (25) 3. Previous smoking of ≥ 20 pack-years 4. Overweight defined as BMI \> 27 kg/m2 5. Age 30 - 75 years 6. Women of childbearing potential must use a safe anti-contraceptive method
Exclusion criteria
1. Chronic treatment with systemic steroids (inhalation steroids allowed) 2. Current smokers 3. Diabetes mellitus type 1 and type 2 as defined by current or previous treatment with antidiabetic medications of any kind or HbA1c ≥ 48mmol/mol 4. Severe hepatic disease (Alanine transferase \> 3 x UNL) 5. Severe impaired renal function (eGFR \< 30ml/min) 6. Congestive heart disease New York Heart Association (NYHA) class 3-4 7. History of acute or chronic pancreatitis 8. History of cholecystitis or cholecystolithiasis 9. Pregnant or breastfeeding women 10. Known bronchial asthma or interstitial lung disease 11. Family history of multiple endocrine neoplasia type 2 (MEN2) or medullary thyroid carcinoma 12. Large goiter or plasma-calcitonin \> 50ng/ml
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Transition Dyspnea Index (TDI) | 40 weeks | The primary objective is to evaluate the effect of Liraglutide 3mg on Transition Dyspnea Index (TDI) after 40 weeks of treatment in subjects with COPD and overweight (BMI\>27 kg/m2). A positive value indicates less dyspnea during specified activities |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in use of bronchodilator drugs and anti-inflammatory drugs | 44 weeks | Defined by an increase in beta2agonists of more than 20 % per week and a change of more than 20 % of dose of anti-inflammatory drugs respectively. |
| 6 minutes walking test | 44 weeks | Walking distance during a 6-minutes walking test |
| Diffusion capacity of the lung for carbon monoxide (DLCO) | 44 weeks | Pulmonary Diffusion Capacity measured by Carbon Monoxide (CO) diffusion capacity test |
| FEV1/FVC | 44 weeks | Forced expiratory volume in first second (FEV1)/forced vital capacity (FVC) |
| Total lung capacity (TLC) | 44 weeks | Total lung capacity |
| Residual volume (RV) | 44 weeks | Residual volume |
| CAT-score | 44 weeks | Chronic Obstructive Pulmonary Disease assessment test, a measure of COPD impact on every day life, total score ranges 0-25, a higher score indicates more symptoms |
| SF-36 | 44 weeks | Short Form (36) Health Survey, which is a Quality of life questionnaire score, subscale scores are calculated according to the SF-36 manual |
| CRP | 44 weeks | Inflammation marker, C-reactive protein, higher value indicates more inflammation |
| Number of COPD exacerbations | 44 weeks | Mild-moderate exacerbations: Treatment with antibiotics or/and oral prednisolone and Moderate-severe exacerbations: Hospitalization due to pulmonary symptoms. |
| MCP-1 | 44 weeks | Inflammation marker, Monocyte Chemoattractant Protein-1, higher value indicates more inflammation |
| Maximal standard uptake value (SUV max) | Twice over 44 weeks | Maximal standard uptake value as measure by FDG-PET/CT scan of the lungs, a higher value indicates more inflammation |
| Mean standard uptake value (SUV mean) | Twice over 44 weeks | Mean standard uptake value as measured by FDG-PET/CT scan of the lungs, a higher value indicates more inflammation |
| Total lesion glycolysis (TLG) | Twice over 44 weeks | Total lesion glycolysis as measured by FDG-PET/CT, a higher value indicates more inflammation |
| Body weight | 44 weeks | Changes in body weight |
| Apnea/hypopnea index (AHI) | Twice during 44 weeks | Apnea/hypopnea index, higher value indicates more apnea/hypopnea episodes |
| Oxygen desaturation index (ODI) | Twice during 44 weeks | Oxygen desaturation index, higher values indicate more episodes of desaturation |
| Epworth score | Twice during 44 weeks | Epworth sleepiness scale questionnaire, total score is calculated, 0-9: Normal, 10-15: mild to moderate sleep apnea, 16 or more indicate severe sleep apnea |
| IL-6 | 44 weeks | Inflammation marker, Interleukine 6, higher values indicates more inflammation |
Countries
Denmark
Outcome results
None listed