Effects of Liraglutide in Chronic Obstructive Pulmonary Disease

Sponsor

Claus Bogh Juhl (Other)

Overall Status

Completed

CT.gov ID

NCT03466021

Collaborator

(none)

Enrollment

Locations

Arms

28.9

Actual Duration (Months)

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Disease, Chronic Obstructive	Drug: Liraglutide Drug: Placebo	Phase 4

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 Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

A prospective, randomized, placebo-controlled, double-blinded, parallel group and two-center trial.A prospective, randomized, placebo-controlled, double-blinded, parallel group and two-center trial.

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Effects of GLP-1 Receptor Agonist Treatment on Pulmonary Function and Quality of Life in Obese Patients With Chronic Obstructive Pulmonary Disease.

Actual Study Start Date :

Jan 1, 2018

Actual Primary Completion Date :

May 31, 2020

Actual Study Completion Date :

May 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Liraglutide Liraglutide injection 3.0 mg daily	Drug: Liraglutide Initially 0.6 mg daily, increasing weekly with 0.6 mg, until 3.0 mg is reached. Other Names: Saxenda NN2211
Placebo Comparator: Placebo Placebo, matching injection pen	Drug: Placebo Matching injection

Arm

Intervention/Treatment

Active Comparator: Liraglutide

Liraglutide injection 3.0 mg daily

Drug: Liraglutide

Initially 0.6 mg daily, increasing weekly with 0.6 mg, until 3.0 mg is reached.

Other Names:

Saxenda

NN2211

Placebo Comparator: Placebo

Placebo, matching injection pen

Drug: Placebo

Matching injection

Outcome Measures

Primary Outcome Measures

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

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
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
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
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.
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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Informed consent obtained before any trial-related activities
COPD as defined by FEV1/FVC<70% after maximal broncho-dilatation and in accordance with the Gold guidelines 2017 (25)
Previous smoking of ≥ 20 pack-years
Overweight defined as BMI > 27 kg/m2
Age 30 - 75 years
Women of childbearing potential must use a safe anti-contraceptive method

Exclusion Criteria:

Chronic treatment with systemic steroids (inhalation steroids allowed)
Current smokers
Diabetes mellitus type 1 and type 2 as defined by current or previous treatment with antidiabetic medications of any kind or HbA1c ≥ 48mmol/mol
Severe hepatic disease (Alanine transferase > 3 x UNL)
Severe impaired renal function (eGFR < 30ml/min)
Congestive heart disease New York Heart Association (NYHA) class 3-4
History of acute or chronic pancreatitis
History of cholecystitis or cholecystolithiasis
Pregnant or breastfeeding women
Known bronchial asthma or interstitial lung disease
Family history of multiple endocrine neoplasia type 2 (MEN2) or medullary thyroid carcinoma
Large goiter or plasma-calcitonin > 50ng/ml