CT-Based Modeling of Bone Micro-Architecture and Fracture-Risk in COPD

Osteoporosis Clinical Trial

Official title:

CT-Based Modeling of Bone Micro-Architecture and Fracture-Risk in COPD

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT03534934
• Other study ID #: 201802724
• Secondary ID: R01HL142042
• Status: Enrolling by invitation
• Phase: N/A
• Start date: February 26, 2019
• Est. completion date: June 1, 2025

Study information

• Verified date: November 2023
• Source: University of Iowa
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 560
• Est. completion date: June 1, 2025
• Est. primary completion date: June 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 45 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Osteoporosis
• Pulmonary Disease, Chronic Obstructive

Intervention

Diagnostic Test:
• Vital signs
Heart rate, respirations, blood pressure, temperature, oxygen saturation arterial oxygen saturation (SaO2), height and weight
• Urine Pregnancy Test
Urine pregnancy test done on woman of childbearing potential.

Other:
• Questionnaires
Subject Questionnaire Calcium Intake Questionnaire Home and Work Activities Survey

Diagnostic Test:
• Blood Test
Blood test for vitamin D level, Hemoglobin A1c, and creatinine level
• Duel-energy X-ray absorptiometry scan
Bone density measurement
• Multi-detector computed tomography
Hip and ankle CT scan
• Dual-energy X-ray absorptiometry scan
Vertebral fracture assessment

Locations

Country	Name	City	State
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Columbia University Medical Center	New York	New York

Sponsors (3)

Lead Sponsor	Collaborator
Punam K Saha	National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incident vertebral fractures	Method: Incident vertebral fracture cases between baseline and three-year follow-up visits will be determined by expert visual reading of baseline and three-year follow-up lateral spine CT scout scans.	Change from baseline and three year follow up visit.
Primary	Prevalent vertebral fractures at baseline	Method: Prevalent fracture cases at the baseline visit will be determined using expert visual reading of the baseline lateral spine CT scout scan.	Baseline Visit
Primary	CT-based fracture-risk	Method: Fragility fracture-risk will be computed using a CT-based model comprising of patient-specific demographic, clinical and radiographic data, CT bone mineral density at the spine, and CT bone micro-structural measures at the ankle.	Baseline Visit
Primary	DXA-based fracture risk	Method: Fragility fracture-risk will be computed using a DXA-based model comprising of patient-specific demographic, clinical and radiographic data, and whole-body, spine, and hip DXA bone mineral density.	Baseline Visit
Secondary	CT bone micro-structural measures at the ankle	Method: CT measures of micro-structure at the ankle will be computed using a high-resolution ankle CT scan and computerized algorithms.	Change from baseline and three year follow up visit
Secondary	CT bone mineral density at the spine	Method: CT measures of thoracic spine bone mineral density will be computed using a chest CT scan and computerized algorithms.	Change from baseline and three year follow up visit
Secondary	DXA Bone Mineral Density	DXA Bone Mineral Density score will be obtained using standard DXA scans.	Change from baseline and three year follow up visit.