Study of COPD Subgroups and Biomarkers (SPIROMICS)

January 10, 2024 updated by: University of North Carolina, Chapel Hill

Subpopulations and Intermediate Outcome Measures in COPD Study

SPIROMICS I and SPIROMICS II are observational studies of Chronic Obstructive Pulmonary Disease (COPD).

SPIROMICS I had two main aims: (1) To find groups of patients with COPD who share certain characteristics; (2) To find new ways of measuring whether or not COPD is getting worse and so provide new ways of testing whether a new treatment is working.

SPIROMICS II has three primary aims. Aim 1 is to define the natural history of "Smokers with symptoms despite preserved spirometry" and characterize the airway mucus abnormalities underlying this condition. Aim 2 is to determine the radiographic precursor lesion(s) for emphysema, and identify the molecular phenotypes underlying airway disease and emphysema. Aim 3 is to advance understanding of the biology of COPD exacerbations through analysis of predisposing baseline phenotypes, exacerbation triggers and host inflammatory response.

Study Overview

Status

Active, not recruiting

Conditions

Detailed Description

SPIROMICS was initially funded through contracts from the NIH. That phase of SPIROMICS is now referred to as SPIROMICS I. SPIROMICS is now funded as a grant from the NIH. The current phase is referred to as SPIROMICS II.

Brief summary of SPIROMICS I:

The purpose of SPIROMICS is to learn about chronic obstructive pulmonary disease (COPD), which is sometimes called emphysema or chronic bronchitis. Millions of Americans have COPD, and it is the fourth leading cause of death in the country. The most common cause of COPD is cigarette smoking, although not all smokers get COPD. The discovery of new treatments for COPD has been slowed by a poor understanding of different types of COPD and a lack of ways to measure whether or not COPD is getting worse.

The study has two main goals. The first is to find groups of patients with COPD who share certain characteristics. Certain groups may respond differently to certain treatments. The second is to find new ways of measuring whether or not COPD is getting worse. This would provide new ways of testing whether a new treatment is working.

SPIROMICS has three substudies and two ancillary studies.

Substudies:

  1. Repeatability Substudy: The entire baseline clinic visit will be repeated on 100 volunteers. The goal of this substudy is to determine reliability of measurement procedures.
  2. Bronchoscopy Substudy: 300 participants will be enrolled for two additional study visits, including a bronchoscopy. The goal of this substudy is to collect and assess biological specimens and relate those results to clinical measurements.
  3. Exacerbation Substudy: Up to 400 participants will be enrolled in this substudy. A daily symptom diary will be collected on all participants. Participants will also be seen in the clinic during a pulmonary exacerbation. The goals of this substudy are to 1) better understand the relationship between symptoms and exacerbations and 2) obtain clinical data and specimens during a pulmonary exacerbation.

Ancillary Studies:

  1. Air Pollution Ancillary Study: The SPIROMICS Air Pollution ancillary study uses state-of-the art air pollution exposure assessments to determine individual-level outdoor and indoor air pollution exposure. The goals of this substudy are to determine the effect of long-term air pollution exposure on COPD morbidity and to determine whether short-term changes in outdoor air pollution are associated with changes in COPD morbidity.
  2. Parametric Response Mapping in COPD: The Parametric Response Mapping (PRM) in COPD ancillary study collects an additional CT scan during the final study visit and uses a new analysis technique (PRM) to assess the functional small airways of the lung and emphysema.

Brief summary of SPIROMICS II:

Aim 1 is to define the natural history of "Smokers with symptoms despite preserved spirometry" and characterize the airway mucus abnormalities underlying this condition. Aim 2 is to determine the radiographic precursor lesion(s) for emphysema, and identify the molecular phenotypes underlying airway disease and emphysema. Aim 3 is to advance understanding of the biology of COPD exacerbations through analysis of predisposing baseline phenotypes, exacerbation triggers and host inflammatory response.

SPIROMICS II will continue follow-up of current participants, with no new enrollment. Each participant will have one clinic visit and will be contacted by telephone every 4 months.

Study Type

Observational

Enrollment (Actual)

2981

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35249
        • University of Alabama at Birmingham
    • California
      • Los Angeles, California, United States, 90095
        • University of California at Los Angeles
      • San Francisco, California, United States, 94143
        • University of California at San Francisco
    • Colorado
      • Denver, Colorado, United States, 80206
        • National Jewish Health
    • Illinois
      • Chicago, Illinois, United States, 60612
        • University of Illinois at Chicago
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa
    • Maryland
      • Baltimore, Maryland, United States, 21224
        • Johns Hopkins University
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan
    • New York
      • New York, New York, United States, 10032
        • Columbia University
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19140
        • Temple University
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Never-smokers, current and former smokers without COPD, and current and former smokers with COPD with access to one of the study clinical centers.

Description

Inclusion Criteria:

  • Between 40 and 80 at baseline visit
  • Never smokers: <1 pack-year history of smoking
  • Never smokers: Must meet lung function criteria based on spirometry without inhaled bronchodilators
  • Current or former smokers: >20 pack-year history of smoking
  • Current or former smokers: Must meet lung function criteria based on spirometry with inhaled bronchodilators

Exclusion Criteria:

  • Dementia or other cognitive dysfunction which in the opinion of the investigator would prevent the participant from consenting to the study or completing study procedures
  • Plans to leave the area in the next 3 years
  • Smoking history of > 1 pack-year but <21 pack-years
  • BMI > 40 kg/m2 at baseline exam
  • Prior significant difficulties with pulmonary function testing
  • Hypersensitivity to or intolerance of albuterol sulfate or ipratropium bromide or propellants or excipients of the inhalers
  • Non-COPD obstructive lung disease, severe kyphoscoliosis, neuromuscular weakness, or other conditions, including clinically significant cardiovascular and pulmonary disease, that, limit the interpretability of the pulmonary function measures.
  • History of Interstitial lung disease
  • History of Lung volume reduction surgery or lung resection
  • History of lung or other organ transplant
  • History of endobronchial valve therapy
  • History of large thoracic metal implants (e.g., AICD (automatic implantable cardioverter/defibrillator) and/or pacemaker)
  • Currently taking >=10mg a day/20mg every other day of prednisone or equivalent systemic corticosteroid
  • Currently taking any immunosuppressive agent
  • Current illicit substance abuse, excluding marijuana
  • History of or current use of IV Ritalin
  • History of or current use of heroin
  • History of illegal IV drug use within the last 10 years or more than 5 instances of illegal IV drug use ever
  • Known HIV/AIDS infection
  • History of lung cancer or any cancer that spread to multiple locations in the body
  • History of or current exposure to chemotherapy or radiation treatments that, in the opinion of the investigator, limits the interpretability of the pulmonary function measures.
  • Diagnosis of unstable cardiovascular disease including myocardial infarction in the past 6 weeks, uncontrolled congestive heart failure, or uncontrolled arrhythmia
  • Any illness expected to cause mortality in the next 3 years
  • Active pulmonary infection, including tuberculosis
  • History of pulmonary embolism in the past 2 years
  • Known diagnosis of primary bronchiectasis
  • Currently institutionalized (e.g., prisons, long-term care facilities)
  • Known to be a first degree relative of another, already enrolled participant (i.e., biological parent, biological sibling)
  • Never smokers only: Current diagnosis of asthma
  • Women only: Cannot be pregnant at baseline or plan to become pregnant during the course of the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Smokers without COPD
Current or former smokers with at least a 20 pack-year history with normal lung function based on post-bronchodilator spirometry (n=944).
Severe COPD
Current and former smokers with at least a 20 pack-year history with severe COPD based on post-bronchodilator spirometry (n=625).
Mild/Moderate COPD
Current and former smokers with at least a 20 pack-year history with mild to moderate COPD based on post-bronchodilator spirometry (n=1210).
Non-smokers
Never-smokers with normal lung function on spirometry without use of bronchodilators (n=201).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Morbidity
Time Frame: Up to end of follow-up (data presented up to month 36)
Morbidity in SPIROMICS will primarily be measured by assessing acute exacerbations in the SPIROMICS cohort.
Up to end of follow-up (data presented up to month 36)
Lung Function
Time Frame: Up to end of follow-up (data presented up to month 36)
COPD is characterized by physiological problems, such as airflow limitations and abnormalities of gas exchange and lung hyperinflation. These features of lung function are accessed objectively in the laboratory setting using spirometry/plethysmography, which can measure such parameters as FEV1 (forced expiratory volume in one second), FVC (forced vital capacity or total volume of air exhaled after full inspiration), FRC (functional residual capacity or volume of gas remaining in the lung at the end of tidal expiration), and IC (inspiratory capacity or maximum volume of gas that can be inspired from end-tidal expiration). The FDA preferred primary endpoint for assessment of alteration in disease progression in COPD is serial measurements of FEV1 over three years.
Up to end of follow-up (data presented up to month 36)
Mortality
Time Frame: Up to end of follow-up (data presented up to month 36)
Deaths of SPIROMICS participants will be identified during follow-up calls and attempts to schedule clinic exams during the three-year study period, and deaths will be recorded in the clinical database. The cause of death will be determined via chart review and adjudication, and deaths attributable to COPD worsening or exacerbation will be recorded as confirmed clinical endpoints, in addition to contributing to the endpoint of all-cause mortality.
Up to end of follow-up (data presented up to month 36)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Repeatability Substudy: Repeatability of clinic visit measurements
Time Frame: Up to end of recruitment (2-6 week measurement repeatability)
The repeatability of clinic visit measurements will be assessed at the end of this substudy. In this substudy all clinic procedures and samples are repeated/recollected 2-6 weeks after the baseline clinic visit in a subset of participants. This provides a measurement of short-term repeatability of these assessments.
Up to end of recruitment (2-6 week measurement repeatability)
Exacerbation Substudy: Assess clinical and biological data in relation to an acute exacerbation
Time Frame: Up to end of follow-up (data presented up to month 15)
The exacerbation substudy will collect clinical and biological measurements during an acute exacerbation in a subset of participants. These will be used to better understand the biological processes underlying an acute exacerbation.
Up to end of follow-up (data presented up to month 15)
Exacerbation Substudy: Assess symptomatic changes in COPD in relation to acute exacerbation
Time Frame: Up to end of follow-up (data presented up to month 15)
The exacerbation substudy will collect a daily symptom diary. Data from this daily diary will be used to characterize the stable versus exacerbative state in a subset of participants.
Up to end of follow-up (data presented up to month 15)
Parametric Response Mapping in COPD: Structural assessment of the lung
Time Frame: Up to end of follow-up (data presented up to month 36)
In the PRM ancillary study, PRM metrics will be used to non-invasively evaluate the regional structural heterogeneity of the lung, including small airways disease and emphysema, and its relationship to clinical measurements.
Up to end of follow-up (data presented up to month 36)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of North Carolina, Chapel Hill

Collaborators

Johns Hopkins University
National Heart, Lung, and Blood Institute (NHLBI)
University of California, Los Angeles
University of Alabama at Birmingham
Columbia University
University of Michigan
University of Iowa
University of Illinois at Chicago
University of California, San Francisco
Temple University
University of Utah
National Jewish Health
COPD Foundation
Wake Forest University

Investigators

  • Principal Investigator: Gerard Criner, MD, Temple University
  • Principal Investigator: David Couper, PhD, University of North Carolina, Chapel Hill
  • Principal Investigator: Graham Barr, PhD, MD, Columbia University
  • Principal Investigator: Eugene Bleecker, MD, University of Arizona
  • Principal Investigator: Robert Paine, MD, University of Utah
  • Principal Investigator: Eric Hoffman, MD, University of Iowa
  • Study Chair: Prescott Woodruff, MD, University of California at San Francisco
  • Principal Investigator: Igor Barjaktarevic, MD, University of California at Los Angeles
  • Principal Investigator: MeiLan Han, MD, University of Michigan
  • Principal Investigator: Russell Bowler, MD, National Jewish Health
  • Principal Investigator: Alejandro Cornellas, MD, University of Iowa
  • Principal Investigator: Nadia Hansel, MD, Johns Hopkins University
  • Principal Investigator: Jerry Krishnan, MD, University of Illinois at Chicago
  • Principal Investigator: Stephen Peters, MD, Wake Forest University
  • Principal Investigator: Mark Dransfield, MD, University of Alabama at Birmingham

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2010

Primary Completion (Estimated)

July 1, 2024

Study Completion (Estimated)

July 1, 2024

Study Registration Dates

First Submitted

October 16, 2013

First Submitted That Met QC Criteria

October 21, 2013

First Posted (Estimated)

October 25, 2013

Study Record Updates

Last Update Posted (Actual)

January 12, 2024

Last Update Submitted That Met QC Criteria

January 10, 2024

Last Verified

January 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 10-0048
  • HHSN268200900020C (Other Identifier: National Heart, Lung, and Blood Institute)
  • HHSN268200900013C (Other Identifier: National Heart, Lung, and Blood Institute)
  • HHSN268200900014C (Other Identifier: National Heart, Lung, and Blood Institute)
  • HHSN268200900015C (Other Identifier: National Heart, Lung, and Blood Institute)
  • HHSN268200900016C (Other Identifier: National Heart, Lung, and Blood Institute)
  • HHSN268200900017C (Other Identifier: National Heart, Lung, and Blood Institute)
  • HHSN268200900018C (Other Identifier: National Heart, Lung, and Blood Institute)
  • HHSN2682009000019C (Other Identifier: National Heart, Lung, and Blood Institute)
  • 5U01HL137880 (U.S. NIH Grant/Contract)
  • 1U24HL141762 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All data collected in SPIROMICS I have been submitted to the NHLBI data repository (BioLINCC). Updates will be submitted regularly during SPIROMICS II

IPD Sharing Time Frame

Data from SPIROMICS I are currently available and will remain available indefinitely.

IPD Sharing Access Criteria

Access criteria for data from BioLINCC are determined by NHLBI, not by the SPIROMICS Investigators.

Criteria for obtaining data directly from SPIROMICS are provided on the web site given below.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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