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

NCT ID: NCT02719184

Last Updated: 2024-08-16

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 463 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-04-13
• Study Completion Date: 2021-06-14

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Healthy subjects

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

No interventions assigned to this group

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.

No interventions assigned to this group

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.

No interventions assigned to this group

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.

No interventions assigned to this group

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.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• 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:

1. mild: post-broncho-dilator FEV1 >=80% of predicted normal (GLI 2012 and JRS 2014) at Visit 1

2. moderate: 50%<= post-broncho-dilator FEV1 < 80% of predicted normal (GLI 2012 and JRS 2014) without chronic respiratory failure at Visit 1

3. 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

Exclusion Criteria

• 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:

1. Put the subject at risk because of participation in the study

2. 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
• A history of cystic fibrosis
• Clinical diagnosis of bronchiectasis requiring specific treatment
• Clinically relevant abnormal baseline hematology and blood chemistry
• Known active tuberculosis
• Patients with change in any therapy within 4 weeks prior to Visit 1
• Current and planned A1AT augmentation therapy
• A malignancy for which the patient has undergone resection, radiation or chemotherapy within past 5 years. Patients with treated basal cell carcinoma or fully cured squamous cell carcinoma are allowed
• Inability to comply with restrictions regarding diet, life style and medication

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

University of California San Diego

San Diego, California, United States

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

Torrance, California, United States

National Jewish Health

Denver, Colorado, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Johns Hopkins University

Baltimore, Maryland, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Temple University Hospital

Philadelphia, Pennsylvania, United States

Baylor College of Medicine

Houston, Texas, United States

Diagnostics Research Group

San Antonio, Texas, United States

University of Utah Health Sciences Center

Salt Lake City, Utah, United States

Brussels - UNIV St-Pierre

Brussels, , Belgium

UZ Leuven

Leuven, , Belgium

University of Alberta Hospital (University of Alberta)

Edmonton, Alberta, Canada

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, Canada

McMaster University Medical Centre

Hamilton, Ontario, Canada

McGill University Health Centre (MUHC)

Montreal, Quebec, Canada

Royal University Hospital

Saskatoon, Saskatchewan, Canada

IUCPQ (Laval University)

Québec, , Canada

Aarhus University Hospital

Aarhus N, , Denmark

Gentofte Hospital

Hellerup, , Denmark

Hvidovre Hospital

Hvidovre, , Denmark

HYKS Keuhkosairauksien tutkimusyksikkö

Helsinki, , Finland

TYKS

Turku, , Finland

IKF Pneumologie GmbH & Co. KG

Frankfurt, , Germany

Pneumologisches Forschungsinstitut an der LungenClinic Grosshansdorf GmbH

Großhansdorf, , Germany

Fraunhofer ITEM

Hanover, , Germany

KLB Gesundheitsforschung Lübeck GmbH

Lübeck, , Germany

Kagoshima University Hospital

Kagoshima, Kagoshima, , Japan

Showa University Fujigaoka Hospital

Kanagawa, Yokohama, , Japan

Kishiwada City Hospital

Osaka, Kishiwada, , Japan

Osaka City University Hospital

Osaka, Osaka, , Japan

Showa University Hospital

Tokyo, Shinagawa-ku, , Japan

Respiratory Medicine Centre, private prac., Bialystok

Bialystok, , Poland

University Clinical Center, Gdansk

Gdansk, , Poland

Institute of Tuberculosis & Lung Disease, Warsaw

Warsaw, , Poland

Konkuk University Medical Center

Seoul, , South Korea

SMG-SNU Boramae Medical Center

Seoul, , South Korea

Korea University Guro Hospital

Seoul, , South Korea

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

Seoul, , South Korea

Hospital del Mar

Barcelona, , Spain

Hospital Vall d'Hebron

Barcelona, , Spain

Hospital Clínic de Barcelona

Barcelona, , Spain

Hospital de Bellvitge

L'Hospitalet de Llobregat, , Spain

Hospital Son Espases

Palma de Mallorca, , Spain

Hospital Quirónsalud Madrid

Pozuelo de Alarcón, , Spain

Skånes universitetssjukhus, Lund

Lund, , Sweden

Queen Elizabeth Hospital

Birmingham, , United Kingdom

Glenfield Hospital

Leicester, , United Kingdom

Royal Free Hospital

London, , United Kingdom

Medicines Evaluation Unit

Manchester, , United Kingdom

Countries

United States; Belgium; Canada; Denmark; Finland; Germany; Japan; Poland; South Korea; Spain; Sweden; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 37978492 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33753437 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.mystudywindow.com

Related Info

Other Identifiers

352.2069

Identifier Type: -

Identifier Source: org_study_id