Clinical trial NCT03534934: CT-Based Modeling of Bone Micro-Architecture and Fracture-Risk in COPD
Official title: CT-Based Modeling of Bone Micro-Architecture and Fracture-Risk in COPD
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Pulmonary Disease, Chronic Obstructive
Osteoporosis
Keywords: COPD
Osteoporosis
Lead sponsor: University of Iowa
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2018-05-23
Enrollment: 560
Sex: ALL
Minimum age (years): 45
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: All subjects will participate in both baseline and three year follow-up visits and undergo identical interventions.
Primary purpose: DIAGNOSTIC

Brief summary: The goal of this translational study is to establish a newly emerging CT-based tool for the characterization of changes in bone micro-architecture and assessment of their implications for fracture-risk in a population of COPD patients at risk for osteoporosis. The tool will be suitable and generalizable across emerging CT scanners from different vendors, and it will provide a more structurally-based assessment of osteoporosis and bone loss than is provided by simple bone density measures. The study will characterize the impact of different COPD-related factors on bone structure, and their implications for fracture-risk, leading to the development of a COPD-specific model for assessment of fracture-risk that will utilize patient-specific demographic, clinical and radiographic data, and CT BMD at the spine, as well as bone structural measures at the hip and/or ankle.

Detailed description: This translational study seeks to establish a Chronic Obstructive Pulmonary Disease (COPD)-specific fracture prediction model using the investigators unique computed tomography (CT)-based assessment of peripheral bone micro-architecture. Osteoporosis, a common comorbidity among patients with COPD, accelerates morbidity and mortality. The basis for this comorbidity is poorly understood, thus the need for characterizing the link between COPD-related factors and bone micro-architecture and their association to fracture-risk. Multiple COPD-related factors are associated with osteoporosis. Different COPD-related causes of bone loss may non-uniformly impact cortical and trabecular bone structures with varying mechanical consequences, reflective of divergent COPD-associated fracture-risk in individuals with similar bone mineral density (BMD). Little is known about this linkage, and the study goal is to fill this knowledge gap using a clinically suitable emerging CT-based tool for characterization of bone micro-architecture at peripheral sites. Specifically, this study will-(1) establish the generalizability of the investigators bone micro-architecture assessment applied to emerging low dose / high resolution CT scanners from different vendors; (2) assess its potential as compared to dual energy x-ray absorptiometry (DXA) to explain prevalent fractures and predict incident fractures among patients with COPD; (3) quantify the impact of different COPD-related factors on bone structures and their implications for fracture-risk; (4) identify COPD subtypes with rapid bone structural degeneration; and (5) develop a COPD-specific model for assessment of fracture-risk using patient-specific data.

The study will take advantage of-(1) existing COPD patient cohorts with lung characterization at the University of Iowa (UI) and Columbia University (CU) representing a wide demographic range; (2) access to emerging CT scanners at both sites; and (3) unique image processing methodologies for quantifying three-dimensional bone structural metrics. The study will recruit 550 smokers with and without COPD from the UI and CU cohorts of the COPDGene and SPIROMICS studies. Smokers without COPD will comprise the control group for the study. At baseline and 3-year follow-up visits, the study team will collect-(1) data related to risk factors; (2) a lateral spine CT scout scan to assess vertebral fractures; (3) high resolution CT scans of the hip and ankle for computation of bone structural metrics; (4) whole-body, spine and hip DXA scans for evaluation of bone mineral density and body composition; and (5) DXA vertebral fracture assessment.

This study will establish an emerging CT-based scanner-independent generalizable tool to assess bone response to different therapeutic interventions aimed at slowing or reversing bone loss, and possibly restoring bone structure, potentially leading to more patient-specific interventions. Also, this study seeks to explain the relationships among various COPD-related factors, bone structural changes and their implications for fracture-risk.

Finally, a COPD-specific model for assessment of fracture-risk will be developed that will utilize patient-specific demographic, clinical and radiographic data, and CT BMD at the spine, as well as bone structural measures at the hip and/or ankle.

Eligibility criteria: Inclusion Criteria:

* Current or former smoker, defined as having at least 10-pack year lifetime history
* Age: 45-90

Subjects will be stratified into groups based on COPD disease status: smokers with COPD and smokers without COPD.

Smokers with COPD will be further stratified into three groups: low emphysema (\< 3%), moderate emphysema (between 3 and 10%), and severe emphysema (\> 10%).

Exclusion Criteria:

* Pregnant or breast-feeding
* Metastatic Malignancy
* Currently receiving dialysis
* Any lower extremity fracture within the last year
* Any lower extremity fracture with hardware implant(s)
* History of bilateral tibia fractures

Primary outcomes:
measure: Incident vertebral fractures
timeFrame: Change from baseline and three year follow up visit.
measure: Prevalent vertebral fractures at baseline
timeFrame: Baseline Visit
measure: CT-based fracture-risk
timeFrame: Baseline Visit
measure: DXA-based fracture risk
timeFrame: Baseline Visit
Secondary outcomes:
measure: CT bone micro-structural measures at the ankle
timeFrame: Change from baseline and three year follow up visit
measure: CT bone mineral density at the spine
timeFrame: Change from baseline and three year follow up visit
measure: DXA Bone Mineral Density
timeFrame: Change from baseline and three year follow up visit.
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
Study officials:
affiliation: University of Iowa
name: Punam Saha, PhD
role: PRINCIPAL_INVESTIGATOR
References: