Effects of Liraglutide in Chronic Obstructive Pulmonary Disease

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03466021
• Other study ID #: U1111-1188-8695
• Status: Completed
• Phase: Phase 4
• Start date: January 1, 2018
• Est. completion date: May 31, 2020

Study information

• Verified date: March 2021
• Source: Hospital of South West Jutland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: May 31, 2020
• Est. primary completion date: May 31, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 30 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Liraglutide
Initially 0.6 mg daily, increasing weekly with 0.6 mg, until 3.0 mg is reached.
• Placebo
Matching injection

Locations

Country	Name	City	State
Denmark	Hospital of South West Jutland	Esbjerg
Denmark	Lillebaelt Hospital	Vejle

Sponsors (1)

Lead Sponsor	Collaborator
Claus Bogh Juhl

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	6 minutes walking test	Walking distance during a 6-minutes walking test	44 weeks
Secondary	Diffusion capacity of the lung for carbon monoxide (DLCO)	Pulmonary Diffusion Capacity measured by Carbon Monoxide (CO) diffusion capacity test	44 weeks
Secondary	FEV1/FVC	Forced expiratory volume in first second (FEV1)/forced vital capacity (FVC)	44 weeks
Secondary	Total lung capacity (TLC)	Total lung capacity	44 weeks
Secondary	Residual volume (RV)	Residual volume	44 weeks
Secondary	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
Secondary	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
Secondary	CRP	Inflammation marker, C-reactive protein, higher value indicates more inflammation	44 weeks
Secondary	IL-6	Inflammation marker, Interleukine 6, higher values indicates more inflammation	44 weeks
Secondary	MCP-1	Inflammation marker, Monocyte Chemoattractant Protein-1, higher value indicates more inflammation	44 weeks
Secondary	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
Secondary	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
Secondary	Total lesion glycolysis (TLG)	Total lesion glycolysis as measured by FDG-PET/CT, a higher value indicates more inflammation	Twice over 44 weeks
Secondary	Body weight	Changes in body weight	44 weeks
Secondary	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
Secondary	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
Secondary	Apnea/hypopnea index (AHI)	Apnea/hypopnea index, higher value indicates more apnea/hypopnea episodes	Twice during 44 weeks
Secondary	Oxygen desaturation index (ODI)	Oxygen desaturation index, higher values indicate more episodes of desaturation	Twice during 44 weeks
Secondary	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