Effects of Liraglutide in Chronic Obstructive Pulmonary Disease

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

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: Liraglutide; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Esbjerg, Denmark, 6700
    • Hospital of South West Jutland
  • Vejle, Denmark, 7100
    • Lillebaelt Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transition Dyspnea Index (TDI)	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	40 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6 minutes walking test	Walking distance during a 6-minutes walking test	44 weeks
Diffusion capacity of the lung for carbon monoxide (DLCO)	Pulmonary Diffusion Capacity measured by Carbon Monoxide (CO) diffusion capacity test	44 weeks
FEV1/FVC	Forced expiratory volume in first second (FEV1)/forced vital capacity (FVC)	44 weeks
Total lung capacity (TLC)	Total lung capacity	44 weeks
Residual volume (RV)	Residual volume	44 weeks
CAT-score	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	44 weeks
SF-36	Short Form (36) Health Survey, which is a Quality of life questionnaire score, subscale scores are calculated according to the SF-36 manual	44 weeks
CRP	Inflammation marker, C-reactive protein, higher value indicates more inflammation	44 weeks
IL-6	Inflammation marker, Interleukine 6, higher values indicates more inflammation	44 weeks
MCP-1	Inflammation marker, Monocyte Chemoattractant Protein-1, higher value indicates more inflammation	44 weeks
Maximal standard uptake value (SUV max)	Maximal standard uptake value as measure by FDG-PET/CT scan of the lungs, a higher value indicates more inflammation	Twice over 44 weeks
Mean standard uptake value (SUV mean)	Mean standard uptake value as measured by FDG-PET/CT scan of the lungs, a higher value indicates more inflammation	Twice over 44 weeks
Total lesion glycolysis (TLG)	Total lesion glycolysis as measured by FDG-PET/CT, a higher value indicates more inflammation	Twice over 44 weeks
Body weight	Changes in body weight	44 weeks
Number of COPD exacerbations	Mild-moderate exacerbations: Treatment with antibiotics or/and oral prednisolone and Moderate-severe exacerbations: Hospitalization due to pulmonary symptoms.	44 weeks
Changes in use of bronchodilator drugs and anti-inflammatory drugs	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.	44 weeks
Apnea/hypopnea index (AHI)	Apnea/hypopnea index, higher value indicates more apnea/hypopnea episodes	Twice during 44 weeks
Oxygen desaturation index (ODI)	Oxygen desaturation index, higher values indicate more episodes of desaturation	Twice during 44 weeks
Epworth score	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	Twice during 44 weeks

Collaborators and Investigators

• Sponsor: Claus Bogh Juhl
• Investigators: Principal Investigator: Claus B Juhl, MD PhD, Hospital of South West Jutland

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Actual): May 31, 2020
• Study Completion (Actual): May 31, 2020

Study Registration Dates

• First Submitted: March 2, 2018
• First Submitted That Met QC Criteria: March 8, 2018
• First Posted (Actual): March 15, 2018

Study Record Updates

• Last Update Posted (Actual): March 16, 2021
• Last Update Submitted That Met QC Criteria: March 12, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: quality of life; Chronic obstructive pulmonary disease; inflammation; GLP-1 receptor agonist; weightloss; FDG/PET-CT
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Liraglutide
• Other Study ID Numbers: U1111-1188-8695

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No