Effects of Liraglutide in Chronic Obstructive Pulmonary Disease

Phase 4

Completed

• Conditions: Pulmonary Disease, Chronic Obstructive
• Interventions: Drug: Placebo; Drug: Liraglutide

• Registration Number: NCT03466021
• Lead Sponsor: Claus Bogh Juhl

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.

Study Timeline

• Study Start: 2018-01-01
• Study First Submitted: 2018-03-02
• Study First Submitted QC: 2018-03-08
• Study First Posted: 2018-03-15
• Primary Completion: 2020-05-31
• Study Completion: 2020-05-31
• Status Verified: 2021-03
• Last Update Submitted: 2021-03-12
• Last Update Posted: 2021-03-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo, matching injection pen
Liraglutide	Liraglutide	Liraglutide injection 3.0 mg daily

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
Oxygen desaturation index (ODI)	Twice during 44 weeks	Oxygen desaturation index, higher values indicate more episodes of desaturation
Total lesion glycolysis (TLG)	Twice over 44 weeks	Total lesion glycolysis as measured by FDG-PET/CT, a higher value indicates more inflammation
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
CRP	44 weeks	Inflammation marker, C-reactive protein, 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
Body weight	44 weeks	Changes in body weight
IL-6	44 weeks	Inflammation marker, Interleukine 6, higher values indicates more inflammation
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
FEV1/FVC	44 weeks	Forced expiratory volume in first second (FEV1)/forced vital capacity (FVC)
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
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.
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
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.
Apnea/hypopnea index (AHI)	Twice during 44 weeks	Apnea/hypopnea index, higher value indicates more apnea/hypopnea episodes

Trial Locations

Locations (2)

Hospital of South West Jutland; 🇩🇰 Esbjerg, Denmark

Lillebaelt Hospital; 🇩🇰 Vejle, Denmark