Longitudinal Follow up to Assess Biomarkers Predictive of Emphysema Progression in Patients With COPD (Chronic Obstructive Pulmonary Disease)

NCT02719184 | Completed Results

• 1 other identifier: 352.2069
• Study Type: observational
• Target: 463
• Locations: 12 countries
• Sites: 51

Brief Summary

The study will include 60 healthy subjects (ex-smoker without any airflow limitation), 125 COPD GOLD (global initiative for chronic obstructive lung disease) I , 125 COPD GOLD II, 125 COPD GOLD III and up to 20 patients with COPD and A1AT (Alpha1-Antitrypsin) deficiency (ZZ genotype). Soluble and imaging biomarkers will be investigated addressing different aspects of disease pathways postulated to be relevant for COPD progression.

Conditions

Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema

Outcome Measures

Primary Outcomes (6)

• Absolute Change From Baseline at Week 156 in Adjusted Lung Density (ALD) Based on Percentile Density at 15% (PD15) Adjusted for Lung Volume

  The absolute change from baseline at Week 156 in adjusted lung density (ALD) based on Percentile Density at 15% (PD15) adjusted for lung volume was reported. The ALD was calculated as: Percentile Density at 15% (PD15) \[gram/Liter (L)\] \* (Inspiratory volume \[L\]/predicted total lung volume \[L\]). The absolute change from baseline in ALD gram/Liter (g/L) was analyzed by Mixed Model for Repeated Measures (MMRM).

  Up to Week 156. Change from baseline value at Week 156 was reported.

• Annual Rate of Lung Function Decline Based on Forced Expiratory Volume in 1 Second (FEV1)

  The annual rate of lung function decline based on Forced Expiratory Volume in 1 second (FEV1) was reported. The annual rate was estimated from a random slope and intercept model with fixed categorical effects of diagnosis group, fixed continuous effects of time \[Year\], and including diagnosis group-by-time interaction. Random effect was included for subject specific intercept and time. Within-subject errors are modelled by an unstructured variance-covariance matrix.

  Up to Week 156

• Number of Participants by the Category of Number of Exacerbations During Study

  Number of participants by the category of number of exacerbations (no exacerbation, 1 exacerbation, or \>= 2 exacerbations) during study was reported.

  Up to Week 156

• Duration of Exacerbations During Study (Per Year)

  The duration of exacerbations for each subject was calculated as: sum of duration of episodes during study (days)\*(365.25/ number of days in study).

  Up to 156 weeks

• Number of Participants With at Least Moderate Exacerbation During Study by the Category of Number of Moderate Exacerbations

  Number of participants with at least moderate exacerbation during study by the category of number of moderate exacerbation (no moderate exacerbation, 1 moderate exacerbation, or \>= 2 moderate exacerbations) was reported.

  Up to 156 weeks

• Number of Participants With Severe Exacerbations During Study by the Category of Number of Severe Exacerbations

  Number of participants with severe exacerbations during study by the category of number of severe exacerbations (no severe exacerbation, 1 severe exacerbation, or \>= 2 severe exacerbations) was reported.

  Up to 156 weeks

Study Arms (5)

Healthy subjects

All eligible healthy subjects were included in this group. The observational period is 156 weeks.

COPD GOLD I

All eligible patients with Chronic Obstructive Pulmonary Disease (COPD) grade 1 according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) were included in this group. The observational period is 156 weeks.

COPD GOLD II

All eligible patients with Chronic Obstructive Pulmonary Disease (COPD) grade 2 according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) were included in this group. The observational period is 156 weeks.

COPD GOLD III

All eligible patients with Chronic Obstructive Pulmonary Disease (COPD) grade 3 according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) were included in this group. The observational period is 156 weeks.

COPD and A1AT Deficiency

All eligible patients with Chronic Obstructive Pulmonary Disease (COPD) and Alpha one anti-trypsin (A1AT) deficiency were included in this group. The observational period is 156 weeks.

Eligibility Criteria

• Age: 40 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Healthy volunteers and COPD patients

You may qualify if:

• Male or female healthy subjects or COPD (GOLD I to III) outpatients with or without A1AT deficiency
• Ex-smokers for at least 9 months with a smoking history of \>=20 pack years
• Signed informed consent consistent with ICH-GCP (International Conference on Harmonisation - Good Clinical Practice) guidelines prior to participation in the study, which includes the application of study restrictions
• Age \>= 40 and \<=70 years
• Body mass index (BMI) of \>= 18 and \<= 35 kg/m2 (\<= 30 kg/m2 in the MRI subset)
• Ability to perform all study related procedures including technically acceptable pulmonary function tests, body plethysmography, DLCO ( Diffusing Capacity of the lungs for Carbon Monoxide) , sputum induction (if applicable), chest CT (Computed Tomography) and MRI (if applicable)
• The current COPD must be mild, moderate or severe based on lung functions and symptoms and the clinical situation must have stabilized for at least 4 weeks prior to Visit 1. The following definitions adapted from the GOLD Guidelines apply:
• mild: post-broncho-dilator FEV1 \>=80% of predicted normal (GLI 2012 and JRS 2014) at Visit 1
• moderate: 50%\<= post-broncho-dilator FEV1 \< 80% of predicted normal (GLI 2012 and JRS 2014) without chronic respiratory failure at Visit 1
• severe: 30%\<= post-bronchodilator FEV1 \<50% of predicted normal (GLI 2012 and JRS 2014) without chronic respiratory failure at Visit 1
• Patients must be on stable therapy (not limited to respiratory medication) for the last 4 weeks prior to Visit 1
• \- Documented A1AT deficiency of ZZ genotype
• Normal lung function values at Visit 1 with a documented post-bronchodilator FEV1 \>=80% of predicted normal (GLI 2012 and JRS 2014) and a post-bronchodilator FEV1/FVC \>= lower limit of normal
• Mean post DLCO over all acceptable measurements at Visit 1 of \>= 70% of predicted normal

You may not qualify if:

• Previous participation in this study or participation in another trial with an investigational drug within 6 weeks prior to Visit 1 or during the study
• Significant pulmonary disease or other significant medical conditions\* (as determined by medical history, examination and clinical investigations at screening) that may in the opinion of the investigator result in any of the following:
• Put the subject at risk because of participation in the study
• Cause concern regarding the subject's ability to participate in this study \*e.g. rheumatoid arthritis, inflammatory bowel disease, severe liver disease, psoriasis, hematological, infectious and psychiatric diseases
• Documented history of asthma. For allergic rhinitis or atopy, source documentation to verify that the subject does not have asthma
• Planned surgery during the study expected to interfere with study procedures and outcome
• Blood withdrawal of more than 100 mL within the past 6 weeks prior to Visit 1 and between Visit 1 and 2
• Significant alcohol or drug abuse within past 2 years prior to Visit 1
• Women who are pregnant, nursing or plan to become pregnant while in the study
• Place of permanent residence of less than 3 months prior to Visit 1
• For the MRI subset: subject who do not meet the following criteria for the MRI assessment at Visit 2: systolic blood pressure between 90 and 180 mmHg (SBP), diastolic blood pressure between 50 and 110 mmHg (DBP), pulse rate between 40 and 110 bpm, ear temperature between 35 - 37.5 C, and a glomerular filtration rate (GFR) \>= 30 mL/min (GFR must not be older than 14 days from the MRI assessment)
• \- Respiratory tract infection or COPD exacerbation in the 4 weeks prior to Visit 1 or during the screening period prior to Visit 2, if rescheduling rules cannot be met
• Newly added anti-inflammatory treatment within 4 weeks prior to Visit 1
• Patients on treatment with PDE (Phosphodiesterase)-5 inhibitors (e.g. Roflumilast) and maintenance treatment Methylxanthines (e.g. Theophylline)
• Hospitalisation for respiratory failure during the year prior to Visit 1

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (51)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

University of California San Diego

San Diego, California, 92103-8415, United States

Location

The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21224, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Diagnostics Research Group

San Antonio, Texas, 78229, United States

Location

University of Utah Health Sciences Center

Salt Lake City, Utah, 84108, United States

Location

Brussels - UNIV St-Pierre

Brussels, 1000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

University of Alberta Hospital (University of Alberta)

Edmonton, Alberta, T6G 1Z1, Canada

Location

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, L8N 4A6, Canada

Location

McMaster University Medical Centre

Hamilton, Ontario, L8N 4K1, Canada

Location

McGill University Health Centre (MUHC)

Montreal, Quebec, H4A 3J1, Canada

Location

Royal University Hospital

Saskatoon, Saskatchewan, S7N 0W8, Canada

Location

IUCPQ (Laval University)

Québec, G1V 4G5, Canada

Location

Aarhus University Hospital

Aarhus N, 8200, Denmark

Location

Gentofte Hospital

Hellerup, 2900, Denmark

Location

Hvidovre Hospital

Hvidovre, 2650, Denmark

Location

HYKS Keuhkosairauksien tutkimusyksikkö

Helsinki, 00029, Finland

Location

TYKS

Turku, 20520, Finland

Location

IKF Pneumologie GmbH & Co. KG

Frankfurt, 60596, Germany

Location

Pneumologisches Forschungsinstitut an der LungenClinic Grosshansdorf GmbH

Großhansdorf, 22927, Germany

Location

Fraunhofer ITEM

Hanover, 30625, Germany

Location

KLB Gesundheitsforschung Lübeck GmbH

Lübeck, 23552, Germany

Location

Kagoshima University Hospital

Kagoshima, Kagoshima, 890-8520, Japan

Location

Showa University Fujigaoka Hospital

Kanagawa, Yokohama, 227-8501, Japan

Location

Kishiwada City Hospital

Osaka, Kishiwada, 596-8501, Japan

Location

Osaka City University Hospital

Osaka, Osaka, 545-8586, Japan

Location

Showa University Hospital

Tokyo, Shinagawa-ku, 142-8666, Japan

Location

Respiratory Medicine Centre, private prac., Bialystok

Bialystok, 15044, Poland

Location

University Clinical Center, Gdansk

Gdansk, 80 952, Poland

Location

Institute of Tuberculosis & Lung Disease, Warsaw

Warsaw, 01138, Poland

Location

Konkuk University Medical Center

Seoul, 05030, South Korea

Location

SMG-SNU Boramae Medical Center

Seoul, 07061, South Korea

Location

Korea University Guro Hospital

Seoul, 08308, South Korea

Location

The Catholic University of Korea, Eunpyeong St. Mary's Hospital

Seoul, 22711, South Korea

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Hospital de Bellvitge

L'Hospitalet de Llobregat, 08907, Spain

Location

Hospital Son Espases

Palma de Mallorca, 07010, Spain

Location

Hospital Quirónsalud Madrid

Pozuelo de Alarcón, 28223, Spain

Location

Skånes universitetssjukhus, Lund

Lund, 221 85, Sweden

Location

Queen Elizabeth Hospital

Birmingham, B15 2GW, United Kingdom

Location

Glenfield Hospital

Leicester, LE3 9QP, United Kingdom

Location

Royal Free Hospital

London, NW3 2PF, United Kingdom

Location

Medicines Evaluation Unit

Manchester, M23 9QZ, United Kingdom

Location

Related Publications (2)

• Crapo JD, Gupta A, Lynch DA, Turner AM, Mroz RM, Janssens W, Ludwig-Sengpiel A, Koegler H, Eleftheraki A, Risse F, Diefenbach C. Baseline characteristics from a 3-year longitudinal study to phenotype subjects with COPD: the FOOTPRINTS study. Respir Res. 2023 Nov 17;24(1):290. doi: 10.1186/s12931-023-02584-2.

  PMID: 37978492 DERIVED

• Crapo J, Gupta A, Lynch DA, Vogel-Claussen J, Watz H, Turner AM, Mroz RM, Janssens W, Ludwig-Sengpiel A, Beck M, Langellier B, Ittrich C, Risse F, Diefenbach C. FOOTPRINTS study protocol: rationale and methodology of a 3-year longitudinal observational study to phenotype patients with COPD. BMJ Open. 2021 Mar 22;11(3):e042526. doi: 10.1136/bmjopen-2020-042526.

  PMID: 33753437 DERIVED

Related Links

• Related Info

Biospecimen

Retention: SAMPLES WITH DNA

Soluble and imaging biomarkers

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

18002430127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2016
• First Posted: March 25, 2016
• Study Start: April 13, 2016
• Primary Completion: June 14, 2021
• Study Completion: June 14, 2021
• Last Updated: August 16, 2024
• Results First Posted: August 16, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: After structured results have been posted, all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.

Locations

FI (2); KR (4); SE (1); BE (2); US (11); CA (6); DK (3); JP (5); PL (3); ES (6); GB (4); DE (4)