Acute Lung Injury, Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
Acute lung injury, Chronic obstructive pulmonary disease (COPD), Whipple procedures, pancreatico-duodenectomies
Brief summary
The aim of study is to determine if 99mTc Annexin V-128 (AxV- 128/Tc) single photon emission computed tomography (SPECT)-computed tomography (CT) can detect perioperative lung injury. The investigators will study patients undergoing major surgery, specifically Whipple procedures (pancreatico-duodenectomies) and compare AxV-128/Tc SPECT-CT scans before and after surgery in Chronic Obstructive Pulmonary Disease (COPD) and non-COPD patients.
Detailed description
Lung injury is commonly not detected unless structural damage has occurred. SPECT-CT scanning using a specific tracer that lights up when it detects apoptosis (programmed cell death) has been used to detect even minor lung injury for example by smoke inhalation in animals and may be more sensitive to detect a less severe injury. The present study aims to study SPECT-CT scan using a tracer for apoptosis, 99mTc Annexin V-128 (AxV- 128/Tc), to detect lung injury after major surgery. Prolonged ventilation during surgery can cause minor lung injury but is usually not clinically detected. The investigators are planning to study 40 patients (20 patients with pre-existing lung disease-COPD and 20 patients with normal preoperative lung function) who are undergoing Whipple operations or other major surgery. The investigators will obtain SPECT-CT scans before and then 2-3 days after surgery and compare the uptake of a radioactive tracer with plasma markers of lung injury (Soluble Receptors for Advanced Glycation End Products (sRAGE), Interleukin 6 (IL-6), Clara-cell 16 and lung surfactant protein D (SP-D) among others). The investigators will ask the subjects to undergo spirometry testing, blood draws and urine collection. In addition, a SPECT-CT scan that lasts approximately 1 hour will be performed prior to surgery and 2-3 days post-operatively (while still hospitalized). 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).
Interventions
RADIATIONSPECT-CT imaging
Injection of AxV-128 labeled with 99mTc followed by SPECT CT
DRUGAxV-128/Tc
Injection of AxV-128 labeled with 99mTc
PROCEDUREWhipple procedure
A Whipple procedure - also known as a pancreaticoduodenectomy - is a complex operation to remove the head of the pancreas, the first part of the small intestine (duodenum), the gallbladder and the bile duct. The Whipple procedure is used to treat tumors and other disorders of the pancreas, intestine and bile duct. It is the most often used surgery to treat pancreatic cancer that's confined to the head of the pancreas. After performing the Whipple procedure, your surgeon reconnects the remaining organs to allow you to digest food normally after surgery. Standard of care.
PROCEDUREMajor surgery
Additional surgical procedure(s) that is clinically indicated. Standard of care.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Columbia University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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) \<0.70 and FEV1 50-79% normal) undergoing Whipple procedures or other major surgeries * Patients with normal lung function undergoing Whipple procedures or other major abdominal surgeries
Exclusion criteria
* Age \< 18 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Correlation of AxV-128/Tc Uptake and Fibrinogen | Up to 1 week from initial scan | To determine if peri-operative lung injury can be detected with in vivo imaging in patients with COPD |
| Correlation of AxV-128/Tc Uptake and C-Reactive Protein (CRP) | Up to 1 week from initial scan | To determine if peri-operative lung injury can be detected with in vivo imaging in patients with COPD |
| Correlation of AxV-128/Tc Uptake and White Blood Cell (WBC) Count | Up to 1 week from initial scan | To determine if peri-operative lung injury can be detected with in vivo imaging in patients with COPD |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation of AxV-128/Tc Uptake and Clara-cell 16 | Up to 1 week from initial scan | To determine if peri-operative lung injury can be detected with in vivo imaging in patients with COPD |
| AxV-128/Tc Uptake | Up to 1 week from initial scan | To determine if peri-operative lung injury can be detected with in vivo imaging in patients with COPD |
| Correlation of AxV-128/Tc Uptake and SP-D | Up to 1 week from initial scan | To determine if peri-operative lung injury can be detected with in vivo imaging in patients with COPD |
| Correlation of AxV-128/Tc Uptake and RAGE | Up to 1 week from initial scan | To determine if peri-operative lung injury can be detected with in vivo imaging in patients with COPD |
| Correlation of AxV-128/Tc Uptake and IL-6 | Up to 1 week from initial scan | To determine if peri-operative lung injury can be detected with in vivo imaging in patients with COPD |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Normal Preoperative Lung Function Patients with normal lung function undergoing Whipple procedures or other major surgeries will receive an injection of AxV-128 labeled with 99mTc followed by SPECT-CT (AxV-128/Tc SPECT-CT imaging).
SPECT-CT imaging: Injection of AxV-128 labeled with 99mTc followed by SPECT CT
AxV-128/Tc: Injection of AxV-128 labeled with 99mTc
Whipple procedure: A Whipple procedure - also known as a pancreaticoduodenectomy - is a complex operation to remove the head of the pancreas, the first part of the small intestine (duodenum), the gallbladder and the bile duct.
The Whipple procedure is used to treat tumors and other disorders of the pancreas, intestine and bile duct. It is the most often used surgery to treat pancreatic cancer that's confined to the head of the pancreas. After performing the Whipple procedure, your surgeon reconnects the remaining organs to allow you to digest food normally after surgery. Standard of care.
Major surgery: Additional surgical procedure(s) that is clinically indicated. Standard of care. | 0 |
| Preoperative COPD Patients with moderate COPD undergoing Whipple procedures or other major surgeries will receive an injection of AxV-128 labeled with 99mTc followed by SPECT-CT (AxV-128/Tc SPECT-CT imaging).
SPECT-CT imaging: Injection of AxV-128 labeled with 99mTc followed by SPECT CT
AxV-128/Tc: Injection of AxV-128 labeled with 99mTc
Whipple procedure: A Whipple procedure - also known as a pancreaticoduodenectomy - is a complex operation to remove the head of the pancreas, the first part of the small intestine (duodenum), the gallbladder and the bile duct.
The Whipple procedure is used to treat tumors and other disorders of the pancreas, intestine and bile duct. It is the most often used surgery to treat pancreatic cancer that's confined to the head of the pancreas. After performing the Whipple procedure, your surgeon reconnects the remaining organs to allow you to digest food normally after surgery. Standard of care.
Major surgery: Additional surgical procedure(s) that is clinically indicated. Standard of care. | 0 |
| Total | 0 |
Baseline characteristics
| Characteristic | — |
|---|---|
| Region of Enrollment United States | — participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Correlation of AxV-128/Tc Uptake and C-Reactive Protein (CRP)
To determine if peri-operative lung injury can be detected with in vivo imaging in patients with COPD
Time frame: Up to 1 week from initial scan
Population: Study terminated due to poor enrollment. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=1).
Primary
Correlation of AxV-128/Tc Uptake and Fibrinogen
To determine if peri-operative lung injury can be detected with in vivo imaging in patients with COPD
Time frame: Up to 1 week from initial scan
Population: Study terminated due to poor enrollment. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=1).
Primary
Correlation of AxV-128/Tc Uptake and White Blood Cell (WBC) Count
To determine if peri-operative lung injury can be detected with in vivo imaging in patients with COPD
Time frame: Up to 1 week from initial scan
Population: Study terminated due to poor enrollment. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=1).
Secondary
AxV-128/Tc Uptake
To determine if peri-operative lung injury can be detected with in vivo imaging in patients with COPD
Time frame: Up to 1 week from initial scan
Population: Study terminated due to poor enrollment. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=1).
Secondary
Correlation of AxV-128/Tc Uptake and Clara-cell 16
To determine if peri-operative lung injury can be detected with in vivo imaging in patients with COPD
Time frame: Up to 1 week from initial scan
Population: Study terminated due to poor enrollment. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=1).
Secondary
Correlation of AxV-128/Tc Uptake and IL-6
To determine if peri-operative lung injury can be detected with in vivo imaging in patients with COPD
Time frame: Up to 1 week from initial scan
Population: Study terminated due to poor enrollment. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=1).
Secondary
Correlation of AxV-128/Tc Uptake and RAGE
To determine if peri-operative lung injury can be detected with in vivo imaging in patients with COPD
Time frame: Up to 1 week from initial scan
Population: Study terminated due to poor enrollment. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=1).
Secondary
Correlation of AxV-128/Tc Uptake and SP-D
To determine if peri-operative lung injury can be detected with in vivo imaging in patients with COPD
Time frame: Up to 1 week from initial scan
Population: Study terminated due to poor enrollment. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=1).