Imaging of Apoptosis in Chronic Obstructive Pulmonary Disease (COPD)

Phase 2

Active, not recruiting

• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Interventions: Radiation: SPECT-CT imaging; Drug: AxV-128/Tc

• Registration Number: NCT02978144
• Lead Sponsor: Columbia University

Brief Summary

This will be a prospective study examining the use of 99mTc-Annexin V-128 (AxV-128/Tc) single-photon emission computed tomography (SPECT)/computerized tomography (CT) technology in the imaging and functional assessment of the lung of patients with chronic obstructive pulmonary disease (COPD), healthy volunteer smokers without COPD and healthy volunteer subjects without smoking history. The aim of study is to determine if patients with COPD have an increased AxV-128/Tc signal with SPECT/CT.

Detailed Description

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death and is characterized by clinical symptoms and spirometry. Additional measures for diagnosis can be taken using imaging modalities such as CT. However, the evaluation of lung destruction in COPD is limited by the inability to visualize the activation of pathological processes since imaging modalities are only able to evaluate end-organ damage. In this proposal, the investigators aim to assess a molecular imaging probe targeting apoptosis, a cellular process known to be pathogenic in COPD. Apoptosis, a process of programmed cellular death, correlates with COPD severity and is not seen in the normal adult lung. In the past several years the investigators have demonstrated the successful ability of AxV-128/Tc to detect apoptosis in vivo in a preclinical animal model of smoke exposure emphysema model. Additionally, Phase 1 studies have demonstrated safety of this agent in healthy patients. Therefore, the investigators will bring AxV-128/Tc forward as a probe to image the apoptotic disease process of the lung in patients with COPD. The investigators will determine if the imaging signal correlates with serum biomarkers of apoptosis and inflammation. It is the investigators' hypothesis that AxV-128/99mTc imaging will show increased uptake in the lungs of patients with COPD, and that this signal intensity will correlate with accepted markers of apoptosis and inflammation. If successful, such an approach will be a powerful tool to potentially predict disease progression after diagnosis, identify patients at risk for disease exacerbation related lung function decline, and monitor response to disease targeted therapy.

The total effective dose from the combined SPECT and CT scans is 6.2 millisievert (mSv). This effective dose is below what a patient receives during a standard 2 dose rest and stress cardiac nuclear imaging study and well within the range of current clinical nuclear imaging tests. The exact long term risk for development of cancer from diagnostic radiological procedures is currently under debate but all imaging procedures in this study are aimed to keep total radiation burden As Low As Reasonably Achievable (ALARA).

Study Timeline

• Study First Submitted: 2016-11-28
• Study First Submitted QC: 2016-11-28
• Study First Posted: 2016-11-30
• Study Start: 2017-06-15
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-25
• Last Update Posted: 2023-07-27
• Primary Completion: 2024-04
• Study Completion: 2024-04

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 34

Inclusion Criteria

• Patients with moderate COPD: Global Initiative for Chronic Obstructive Lung Disease (GOLD) Stage II, forced expiratory volume 1 (FEV1)/forced vital capacity (FVC) < 0.7 and FEV1 50-79% predicted
• Patients with severe COPD: GOLD Stage III-IV, FEV1/FVC < 0.7 and FEV1 < 50% predicted
• Healthy controls who are currently smoking (> 10 pack years) with normal spirometry (FEV1 > 80% and FEV1/FVC > 70%)
• Healthy controls who never smoked (less than 100 lifetime cigarettes) with normal spirometry (FEV1 > 80% and FEV1/FVC > 70%)

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Exclusion Criteria

• Age < 18 years

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Patients with moderate COPD	SPECT-CT imaging	Patients with moderate COPD will be injected with AxV-128 labeled with 99mTc followed by SPECT-CT (AxV-128/Tc SPECT-CT imaging).
Healthy volunteers	SPECT-CT imaging	Healthy controls who never smoked (less than 100 lifetime cigarettes) with normal spirometry will be injected with AxV-128 labeled with 99mTc followed by SPECT-CT (AxV-128/Tc SPECT-CT imaging).
Healthy volunteers	AxV-128/Tc	Healthy controls who never smoked (less than 100 lifetime cigarettes) with normal spirometry will be injected with AxV-128 labeled with 99mTc followed by SPECT-CT (AxV-128/Tc SPECT-CT imaging).
Patients with severe COPD	AxV-128/Tc	Patients with severe COPD will be injected with AxV-128 labeled with 99mTc followed by SPECT-CT (AxV-128/Tc SPECT-CT imaging).
Current smokers	SPECT-CT imaging	Healthy controls who are currently smoking (\> 10 pack years) with normal spirometry will be injected with AxV-128 labeled with 99mTc followed by SPECT-CT (AxV-128/Tc SPECT-CT imaging).
Patients with moderate COPD	AxV-128/Tc	Patients with moderate COPD will be injected with AxV-128 labeled with 99mTc followed by SPECT-CT (AxV-128/Tc SPECT-CT imaging).
Patients with severe COPD	SPECT-CT imaging	Patients with severe COPD will be injected with AxV-128 labeled with 99mTc followed by SPECT-CT (AxV-128/Tc SPECT-CT imaging).
Current smokers	AxV-128/Tc	Healthy controls who are currently smoking (\> 10 pack years) with normal spirometry will be injected with AxV-128 labeled with 99mTc followed by SPECT-CT (AxV-128/Tc SPECT-CT imaging).

Primary Outcome Measures

Name	Time	Method
Mean AxV-128/Tc Uptake	Up to 18 months from the initial scan	Mean ± standard deviation (SD) for values for uptake of AxV-128/Tc for individual lobes and for lungs will be determined for each COPD group and compared using unpaired t-test for values with Gaussian distribution and Mann Whitney (Wilcoxon rank) test for continuous variables without normal distribution.

Trial Locations

Locations (1)

Columbia University Irving Medical Center; 🇺🇸 New York, New York, United States