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Hyperpolarized 129Xe MRI for the Assessment of BOS With Late Onset LONIPC (BOS-MRI)

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ClinicalTrials.gov Identifier: NCT04029636
Recruitment Status : Not yet recruiting
First Posted : July 23, 2019
Last Update Posted : July 23, 2019
Sponsor:
Information provided by (Responsible Party):
Jane Turner, Hamilton Health Sciences Corporation

Brief Summary:
The development of bronchiolitis obliterans syndrome (BOS) and other late onset non-infectious pulmonary complications (LONIPCs) following hematopoietic stem cell transplantation (HSCT) is associated with a significantly worse prognosis, high disease burden, and excessive health resource utilization. In this proposal, the investigators plan to examine and compare different diagnostic modalities which can provide detailed physiological and anatomical characterization of LONIPCs.

Condition or disease Intervention/treatment
Bronchiolitis Obliterans Other: Inhaled Hyperpolarized Xenon-129

Detailed Description:
There is mounting evidence suggesting that current practice is failing to provide early detection of LONIPCs, before critical loss of lung function occurs. Furthermore, autopsy series in HSCT patients have revealed a wide spectrum of pulmonary pathology in different compartments of the lung (airway, parenchyma, interstitium) within the same individual. These findings imply that LONIPCs and the extent of their pulmonary involvement are under-recognized, which adversely impacts the clinical trajectory and outcomes of HSCT patients. These findings also suggest that the underlying pathophysiology is multi-faceted and diffuse, highlighting a need for a multi-modal approach to early detection, and better characterization of the spectrum of pulmonary involvement. In this study, we plan to examine and compare different diagnostic modalities which can provide detailed physiological and anatomical characterization of LONIPCs. We propose an observational study using hyperpolarized magnetic resonance imaging (MRI) to capture the anatomical and functional spectrum of LONIPCs post-HSCT. Hyperpolarized magnetic resonance imaging (MRI) is a novel and noninvasive functional imaging method, with the capacity to evaluate pulmonary structure and function. Inhaled hyperpolarized gas (129Xenon) maps focal areas of ventilation defects, a functional consequence of small airway obstruction, which often goes undetected on PFT in early disease states. It can provide additional information on alveolar structure and gas diffusion, lending insight into pathology in other compartments. Oscillometry technique (FOT) is a non-invasive technique using wave frequency to map out large and small airways, commonly used in pediatric pulmonology. We propose to examine the 2 novel modalities in HSCT patients with and without LONIPC/BOS. We hypothesize that the use of functional-structural imaging and FOT will provide better characterization and the extent of LONIPCs in early diseases states post-HSCT. These findings will provide invaluable insight into the pathophysiology of LONIPCs, providing a platform for future research into the early diagnosis and treatment of these high-burden diseases.

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Study Type : Observational
Estimated Enrollment : 45 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Hyperpolarized 129Xe Magnetic Resonance Imaging for the Early Detection of Bronchiolitis Obliterans Syndrome (BOS) and Other Late Onset Non-infectious Pulmonary Complications (LONIPCs) Following Hematopoietic Stem Cell Transplantation
Estimated Study Start Date : August 2019
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : November 2021

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Established LONIPC
The first cohort will comprise of patients with established LONIPCs and the investigative procedures in this study will provide data on the scope of abnormalities and pathology across the spectrum of these conditions.
Other: Inhaled Hyperpolarized Xenon-129
How hyperpolarized 129Xe MRI measurements of lung structure and function change over time in a population at high risk for LONIPC related to their transplant

Trajectory of LONIPC
The second, prospectively followed, cohort will provide data on the sequence and temporal development of these abnormalities, and therefore provide information on the trajectory of LONIPCs
Other: Inhaled Hyperpolarized Xenon-129
How hyperpolarized 129Xe MRI measurements of lung structure and function change over time in a population at high risk for LONIPC related to their transplant




Primary Outcome Measures :
  1. The change detected in Ventilation Defect Percent (VDP) on 129Xe MRI imaging in cross-sectional and prospectively followed cohorts. [ Time Frame: MRIs will be performed every three months for one year. ]
    129Xe Ventilation Defect Percent (VDP): For analysis of 129Xe static ventilation MR images we will employ the same approach as described by Kirby and colleagues to quantify the VDP to assess ventilation. VDP is expressed as a percentage.

  2. The change detected in Apparent Diffusion Coefficients (ADC) on 129Xe MRI imaging in cross-sectional and prospectively followed cohorts. [ Time Frame: MRIs will be performed every three months for one year. ]
    129Xe Apparent Diffusion Coefficients (ADC): For analysis of 129Xe diffusion-weighted MR images we will employ the same approach as described by Kirby and colleagues to quantify the ADC and generate ADC maps to assess airspace size. ADC is expressed in mm^2/s.

  3. The change detected in Signal-to-noice Ration (SNR) on 129Xe MRI imaging in cross-sectional and prospectively followed cohorts. [ Time Frame: MRIs will be performed every three months for one year. ]
    129Xe Signal-to-noise Ratio (SNR): The signal-to-noise ratio will be calculated as the mean signal intensity in a region of interest within the lung divided by the standard deviation in a region of interest outside of the lung.

  4. The change detected in forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), total lung capacity (TLC), and residual volume (RV) in cross-sectional and prospectively followed cohorts. [ Time Frame: Pulmonary Function Tests (PFTs) will be performed as clinically indicated, which in this study population will be every three months for two years. ]
    FVC, FEV1, TLC, and RV will be documented in litres (L) through pulmonary function testing.

  5. The change detected in FEV1/FVC ratio and RV/TLC ratio in cross-sectional and prospectively followed cohorts. [ Time Frame: PFTs will be performed as clinically indicated, which in this study population will be every three months for two years. ]
    FEV1/FVC ratio and RV/TLC ratio will be documented; these are ratios therefore and therefore do not have units.

  6. The change detected in diffusion capacity of the lung for carbon monoxide (DLCO) and DLCO corrected for hemoglobin in cross-sectional and prospectively followed cohorts. [ Time Frame: PFTs will be performed as clinically indicated, which in this study population will be every three months for two years. ]
    Diffusion capacity of the lung for carbon monoxide (DLCO) and DLCO corrected for hemoglobin will be recorded in L/min/mmHg.

  7. The change detected in DLCO divided by alveolar volume (VA) [DLCO/VA, or transfer coefficient of the lung for carbon monoxide, KCO] in cross-sectional and prospectively followed cohorts. [ Time Frame: PFTs will be performed as clinically indicated, which in this study population will be every three months for two years. ]
    DLCO divided by alveolar volume (DLCO/VA, or transfer coefficient of the lung for carbon monoxide [KCO]) will be recorded in mL/min/mmHg/L

  8. The change detected in forced oscillometry technique (FOT) in cross-sectional and prospectively followed cohorts. [ Time Frame: Oscillometry will be recorded every three months for one year. ]
    Results recorded in hertz (Hz)


Secondary Outcome Measures :
  1. Change in airway resistance and reactance over time quantified by FOT [ Time Frame: Oscillometry will be recorded every three months for one year. ]
    Measured in ohms (Ω)

  2. Development of Bronchiolitis Obliterans Syndrome (BOS) [ Time Frame: Development of BOS will be documented over the study's duration (2 years). ]
    The development of BOS will be defined using the National Institutes of Health (NIH) diagnostic criteria, and documented for all study participants (yes/no).

  3. Development of clinical outcomes of death, hospitalization for respiratory cause, or respiratory failure. [ Time Frame: Outcomes will be documented over the study's duration (2 years). ]
    The development of the above clinical outcomes will be documented for all study participants (yes/no).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
  1. For participants who have known LONIPC at enrollment (cross-sectional group)
  2. For participants who have no known LONIPC, but are at risk by virtue of recently-diagnosed cGVHD
Criteria

Inclusion Criteria:

  • For participants who have known LONIPC at enrollment (cross-sectional group):

    • Patient is 18 - 70 years old
    • Patient has received an allogenic HSCT
    • Diagnosed LONIPC

For participants who have no known LONIPC, but are at risk by virtue of recently-diagnosed cGVHD:

  • Patient is 18 - 70 years old
  • Patient has received an allogenic HSCT in the last 24 months
  • Patient has a new diagnosis of cGVHD within the last 6 months by criteria of:

    • Moderate- or severe- cGVHD as per NIH consensus criteria, determined by a treating hematologist or
    • cGVHD requiring immunosuppression with prednisone at a dose of > 0.5mg/kg/day, or alternate steroid-sparing agent

Exclusion Criteria:

  • For participants who have known LONIPC at enrollment (cross-sectional group):

    • Age less than 18 years or greater than 70 years of age
    • Current smoker (quit in the last 3 months)
    • Smoking history greater than 20 pack years
    • Presence of contraindications to pulmonary function testing including myocardial infarction within the last one month, hemoptysis, active communicable disease (e.g. TB), inability to follow commands, thoracic/abdominal/eye surgery within the last 3 months, pneumothorax, uncontrolled hypertension (SBP > 180, DBP > 110) or pulmonary embolism, other contraindication as determined by technical staff.
    • Pregnancy prior to or during study
    • In the opinion of the investigator, subject is mentally or legally incapacitated, preventing informed consent from being obtained, or cannot read or understand the written material
    • Patient has an implanted mechanically, electrically or magnetically activated device or any metal in their body which cannot be removed, including but not limited to pacemakers, neurostimulators, biostimulators, implanted insulin pumps, aneurysm clips, bio-prosthesis, artificial limb, metallic fragment or foreign body, shunt, surgical staples (including clips or metallic sutures and/or ear implants) (at the discretion of the MRI Technologist/3T Manager)
    • In the investigator's opinion, subject suffers from any physical, psychological or other condition(s) that might prevent performance of the MRI, such as severe claustrophobia

For participants who have no known LONIPC, but are at risk by virtue of recently-diagnosed cGVHD:

  • Age less than 18 years or greater than 70 years of age
  • Known history of late onset non-infectious pulmonary complication (LONIPC) related to HSCT
  • Current smoker (quit in the last 3 months)
  • Smoking history greater than 20 pack years
  • Presence of contraindications to pulmonary function testing including myocardial infarction within the last one month, hemoptysis, active communicable disease (e.g. TB), inability to follow commands, thoracic/abdominal/eye surgery within the last 3 months, pneumothorax, uncontrolled hypertension (SBP > 180, DBP > 110) or pulmonary embolism, other contraindication as determined by technical staff.
  • Pregnancy prior to or during study
  • In the opinion of the investigator, subject is mentally or legally incapacitated, preventing informed consent from being obtained, or cannot read or understand the written material
  • Patient has an implanted mechanically, electrically or magnetically activated device or any metal in their body which cannot be removed, including but not limited to pacemakers, neurostimulators, biostimulators, implanted insulin pumps, aneurysm clips, bio-prosthesis, artificial limb, metallic fragment or foreign body, shunt, surgical staples (including clips or metallic sutures and/or ear implants) (at the discretion of the MRI Technologist/3T Manager)
  • In the investigator's opinion, subject suffers from any physical, psychological or other condition(s) that might prevent performance of the MRI, such as severe claustrophobia

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04029636


Contacts
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Contact: Jane Turner, MD 905-906-2629 jane.turner@medportal.ca
Contact: Sarah Svenningsen, PhD 905-522-1155 ext 37313 svennins@mcmaster.ca

Locations
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Canada, Ontario
Hamilton Health Sciences
Hamilton, Ontario, Canada, L8V 1C3
Contact: Jane Turner, MD    905-906-2629    jane.turner@medportal.ca   
Sponsors and Collaborators
Hamilton Health Sciences Corporation

Publications:
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Responsible Party: Jane Turner, Principal Investigator, Hamilton Health Sciences Corporation
ClinicalTrials.gov Identifier: NCT04029636    
Other Study ID Numbers: 5996
First Posted: July 23, 2019    Key Record Dates
Last Update Posted: July 23, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Bronchiolitis
Bronchiolitis Obliterans
Bronchitis
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Infections