Imaging of Apoptosis in Chronic Obstructive Pulmonary Disease (COPD)

• ClinicalTrials.gov Identifier: NCT02978144
• Recruitment Status: Recruiting
• First Posted: November 30, 2016
• Last Update Posted: July 28, 2021
• Sponsor: Columbia University
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): Columbia University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Chronic Obstructive Pulmonary Disease (COPD)	Radiation: SPECT-CT imaging; Drug: AxV-128/Tc	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 32 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: In Vivo Imaging of Destructive Processes in Chronic Obstructive Pulmonary Disease (COPD)
• Actual Study Start Date: June 15, 2017
• Estimated Primary Completion Date: July 2022
• Estimated Study Completion Date: July 2022

Arms and Interventions

Arm	Intervention/treatment
Healthy volunteers; 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).	Radiation: SPECT-CT imaging; Injection of AxV-128 labeled with 99mTc followed by SPECT-CT; Drug: AxV-128/Tc; Injection of AxV-128 labeled with 99mTc
Current smokers; 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).	Radiation: SPECT-CT imaging; Injection of AxV-128 labeled with 99mTc followed by SPECT-CT; Drug: AxV-128/Tc; Injection of AxV-128 labeled with 99mTc
Patients with moderate COPD; Patients with moderate COPD will be injected with AxV-128 labeled with 99mTc followed by SPECT-CT (AxV-128/Tc SPECT-CT imaging).	Radiation: SPECT-CT imaging; Injection of AxV-128 labeled with 99mTc followed by SPECT-CT; Drug: AxV-128/Tc; Injection of AxV-128 labeled with 99mTc
Patients with severe COPD; Patients with severe COPD will be injected with AxV-128 labeled with 99mTc followed by SPECT-CT (AxV-128/Tc SPECT-CT imaging).	Radiation: SPECT-CT imaging; Injection of AxV-128 labeled with 99mTc followed by SPECT-CT; Drug: AxV-128/Tc; Injection of AxV-128 labeled with 99mTc

Outcome Measures

Primary Outcome Measures :

1. Mean AxV-128/Tc Uptake [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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%)

Exclusion Criteria:

• Age < 18 years

Contacts and Locations

Contacts

Contact: Lynne Johnson, MD; (212) 305-5794; lj2129@cumc.columbia.edu

Contact: Jeanine D'Armiento, MD PhD; (212) 305-3745; jmd12@cumc.columbia.edu

Locations

United States, New York

Columbia University Medical Center; Recruiting

New York, New York, United States, 10032

Contact: Gebhard Wagener, MD 212-305-6494 gw72@cumc.columbia.edu

Sponsors and Collaborators

Columbia University

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Gebhard Wagener, MD; Columbia University

More Information

• Responsible Party: Columbia University
• ClinicalTrials.gov Identifier: NCT02978144
• Other Study ID Numbers: AAAR0417; 1R01HL131960-01 ( U.S. NIH Grant/Contract )
• First Posted: November 30, 2016
• Last Update Posted: July 28, 2021
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Columbia University:

Chronic Obstructive Pulmonary Disease (COPD)

Additional relevant MeSH terms:

Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases