Imaging of Peri-operative (periOP) Lung Injury

In Vivo Imaging of Peri-operative (periOP) Destructive Processes in the Lung

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.

Study Overview

• Status: Terminated
• Conditions: Acute Lung Injury; Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Drug: AxV-128/Tc; Radiation: SPECT-CT imaging; Procedure: Whipple procedure; Procedure: Major surgery

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).

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 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).	Drug: AxV-128/Tc; Injection of AxV-128 labeled with 99mTc; Other Names: 99mTc-rhAnnexin V-128; Radiation: SPECT-CT imaging; Injection of AxV-128 labeled with 99mTc followed by SPECT CT; Other Names: SPECT CT; Procedure: 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.; Other Names: Pancreaticoduodenectomy; Procedure: Major surgery; Additional surgical procedure(s) that is clinically indicated. Standard of care.; Other Names: Surgical procedure
Other: 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).	Drug: AxV-128/Tc; Injection of AxV-128 labeled with 99mTc; Other Names: 99mTc-rhAnnexin V-128; Radiation: SPECT-CT imaging; Injection of AxV-128 labeled with 99mTc followed by SPECT CT; Other Names: SPECT CT; Procedure: 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.; Other Names: Pancreaticoduodenectomy; Procedure: Major surgery; Additional surgical procedure(s) that is clinically indicated. Standard of care.; Other Names: Surgical procedure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Up to 1 week from initial scan
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	Up to 1 week from initial scan
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	Up to 1 week from initial scan

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AxV-128/Tc Uptake	To determine if peri-operative lung injury can be detected with in vivo imaging in patients with COPD	Up to 1 week from initial scan
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	Up to 1 week from initial scan
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	Up to 1 week from initial scan
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	Up to 1 week from initial scan
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	Up to 1 week from initial scan

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2018
• Primary Completion (Actual): February 5, 2020
• Study Completion (Actual): February 5, 2020

Study Registration Dates

• First Submitted: November 28, 2016
• First Submitted That Met QC Criteria: November 29, 2016
• First Posted (Estimate): December 1, 2016

Study Record Updates

• Last Update Posted (Actual): September 14, 2021
• Last Update Submitted That Met QC Criteria: August 17, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Chronic obstructive pulmonary disease (COPD); Acute lung injury; Whipple procedures; pancreatico-duodenectomies
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Wounds and Injuries; Thoracic Injuries; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Acute Lung Injury; Lung Injury
• Other Study ID Numbers: AAAR0395; 1R01HL131960-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No