Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
Chronic Obstructive Pulmonary Disease (COPD), Phase 2
Brief summary
This is a prospective interventional study examining the use of Annexin - a radioactive tracer, in assessing lung damage in healthy volunteers, healthy volunteers actively smoking, and patients with moderate and severe chronic obstructive pulmonary disease (COPD). All study participants will undergo a CT scan, pulmonary testing, and blood test. The study procedures are done in one day. The aim of this study is to determine if Annexin can be used as a marker to detect lung injury early on and aid in the future diagnosis of COPD.
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 the current study, 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 99mTc-Annexin V-128 (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 single-photon emission computed tomography (SPECT) and computerized tomography (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).
Interventions
DRUGAxV-128/Tc
Study drug 99mTc-Annexin V-128 (AxV-128/Tc) is administered intravenously prior to SPECT/CT imaging.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Columbia University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
All study participants will receive study drug Annexin.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean AxV-128/Tc Uptake | At first visit (Day 1) and if available, at 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants All study participants will be administered Annexin (study drug also known as 99mTc-Annexin V-128 (AxV-128/Tc)) intravenously (IV) followed by SPECT-CT imaging scan.
AxV-128/Tc: Study drug 99mTc-Annexin V-128 (AxV-128/Tc) is administered intravenously prior to SPECT/CT imaging. | 34 |
| Total | 34 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Customized 18 - 39 years | 0 Participants |
| Age, Customized 40 - 59 years | 14 Participants |
| Age, Customized 60 - 79 years | 20 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 24 Participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 34 |
| other Total, other adverse events | 0 / 34 |
| serious Total, serious adverse events | 0 / 34 |
Outcome results
Primary
Mean AxV-128/Tc Uptake
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.
Time frame: At first visit (Day 1) and if available, at up to 18 months from the initial scan
Population: Data was not collected. Participants were enrolled prior to the study termination but were not administered the study intervention due to inability to obtain a drug supplier.