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Effects of Liraglutide in Chronic Obstructive Pulmonary Disease

Primary Purpose

Pulmonary Disease, Chronic Obstructive

Status
Completed
Phase
Phase 4
Locations
Denmark
Study Type
Interventional
Intervention
Liraglutide
Placebo
Sponsored by
Claus Bogh Juhl
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Disease, Chronic Obstructive focused on measuring GLP-1 receptor agonist, Chronic obstructive pulmonary disease, FDG/PET-CT, inflammation, weightloss, quality of life

Eligibility Criteria

30 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Hospital of South West Jutland
  • Lillebaelt Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Liraglutide

Placebo

Arm Description

Liraglutide injection 3.0 mg daily

Placebo, matching injection pen

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
March 2, 2018
Last Updated
March 12, 2021
Sponsor
Claus Bogh Juhl
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1. Study Identification

Unique Protocol Identification Number
NCT03466021
Brief Title
Effects of Liraglutide in Chronic Obstructive Pulmonary Disease
Official Title
Effects of GLP-1 Receptor Agonist Treatment on Pulmonary Function and Quality of Life in Obese Patients With Chronic Obstructive Pulmonary Disease.
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
January 1, 2018 (Actual)
Primary Completion Date
May 31, 2020 (Actual)
Study Completion Date
May 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Claus Bogh Juhl

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Disease, Chronic Obstructive
Keywords
GLP-1 receptor agonist, Chronic obstructive pulmonary disease, FDG/PET-CT, inflammation, weightloss, quality of life

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
A prospective, randomized, placebo-controlled, double-blinded, parallel group and two-center trial.
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Liraglutide
Arm Type
Active Comparator
Arm Description
Liraglutide injection 3.0 mg daily
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo, matching injection pen
Intervention Type
Drug
Intervention Name(s)
Liraglutide
Other Intervention Name(s)
Saxenda, NN2211
Intervention Description
Initially 0.6 mg daily, increasing weekly with 0.6 mg, until 3.0 mg is reached.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching injection
Primary Outcome Measure Information:
Title
Transition Dyspnea Index (TDI)
Description
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
Time Frame
40 weeks
Secondary Outcome Measure Information:
Title
6 minutes walking test
Description
Walking distance during a 6-minutes walking test
Time Frame
44 weeks
Title
Diffusion capacity of the lung for carbon monoxide (DLCO)
Description
Pulmonary Diffusion Capacity measured by Carbon Monoxide (CO) diffusion capacity test
Time Frame
44 weeks
Title
FEV1/FVC
Description
Forced expiratory volume in first second (FEV1)/forced vital capacity (FVC)
Time Frame
44 weeks
Title
Total lung capacity (TLC)
Description
Total lung capacity
Time Frame
44 weeks
Title
Residual volume (RV)
Description
Residual volume
Time Frame
44 weeks
Title
CAT-score
Description
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
Time Frame
44 weeks
Title
SF-36
Description
Short Form (36) Health Survey, which is a Quality of life questionnaire score, subscale scores are calculated according to the SF-36 manual
Time Frame
44 weeks
Title
CRP
Description
Inflammation marker, C-reactive protein, higher value indicates more inflammation
Time Frame
44 weeks
Title
IL-6
Description
Inflammation marker, Interleukine 6, higher values indicates more inflammation
Time Frame
44 weeks
Title
MCP-1
Description
Inflammation marker, Monocyte Chemoattractant Protein-1, higher value indicates more inflammation
Time Frame
44 weeks
Title
Maximal standard uptake value (SUV max)
Description
Maximal standard uptake value as measure by FDG-PET/CT scan of the lungs, a higher value indicates more inflammation
Time Frame
Twice over 44 weeks
Title
Mean standard uptake value (SUV mean)
Description
Mean standard uptake value as measured by FDG-PET/CT scan of the lungs, a higher value indicates more inflammation
Time Frame
Twice over 44 weeks
Title
Total lesion glycolysis (TLG)
Description
Total lesion glycolysis as measured by FDG-PET/CT, a higher value indicates more inflammation
Time Frame
Twice over 44 weeks
Title
Body weight
Description
Changes in body weight
Time Frame
44 weeks
Title
Number of COPD exacerbations
Description
Mild-moderate exacerbations: Treatment with antibiotics or/and oral prednisolone and Moderate-severe exacerbations: Hospitalization due to pulmonary symptoms.
Time Frame
44 weeks
Title
Changes in use of bronchodilator drugs and anti-inflammatory drugs
Description
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.
Time Frame
44 weeks
Title
Apnea/hypopnea index (AHI)
Description
Apnea/hypopnea index, higher value indicates more apnea/hypopnea episodes
Time Frame
Twice during 44 weeks
Title
Oxygen desaturation index (ODI)
Description
Oxygen desaturation index, higher values indicate more episodes of desaturation
Time Frame
Twice during 44 weeks
Title
Epworth score
Description
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
Time Frame
Twice during 44 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Claus B Juhl, MD PhD
Organizational Affiliation
Hospital of South West Jutland
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital of South West Jutland
City
Esbjerg
ZIP/Postal Code
6700
Country
Denmark
Facility Name
Lillebaelt Hospital
City
Vejle
ZIP/Postal Code
7100
Country
Denmark

12. IPD Sharing Statement

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Effects of Liraglutide in Chronic Obstructive Pulmonary Disease

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