Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Imaging of Apoptosis in Chronic Obstructive Pulmonary Disease (COPD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02978144
Recruitment Status : Recruiting
First Posted : November 30, 2016
Last Update Posted : December 18, 2019
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Gebhard Wagener, Columbia University

Tracking Information
First Submitted Date  ICMJE November 28, 2016
First Posted Date  ICMJE November 30, 2016
Last Update Posted Date December 18, 2019
Actual Study Start Date  ICMJE June 15, 2017
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 28, 2016)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Imaging of Apoptosis in Chronic Obstructive Pulmonary Disease (COPD)
Official Title  ICMJE In Vivo Imaging of Destructive Processes in Chronic Obstructive Pulmonary Disease (COPD)
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Chronic Obstructive Pulmonary Disease (COPD)
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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).
    Interventions:
    • Radiation: SPECT-CT imaging
    • Drug: AxV-128/Tc
  • 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).
    Interventions:
    • Radiation: SPECT-CT imaging
    • Drug: AxV-128/Tc
  • 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).
    Interventions:
    • Radiation: SPECT-CT imaging
    • Drug: AxV-128/Tc
  • 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).
    Interventions:
    • Radiation: SPECT-CT imaging
    • Drug: AxV-128/Tc
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 28, 2016)
32
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2021
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Lynne Johnson, MD (212) 305-5794 lj2129@cumc.columbia.edu
Contact: Jeanine D'Armiento, MD PhD (212) 305-3745 jmd12@cumc.columbia.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02978144
Other Study ID Numbers  ICMJE AAAR0417
1R01HL131960-01 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Gebhard Wagener, Columbia University
Study Sponsor  ICMJE Columbia University
Collaborators  ICMJE National Heart, Lung, and Blood Institute (NHLBI)
Investigators  ICMJE
Principal Investigator: Gebhard Wagener, MD Columbia University
PRS Account Columbia University
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP