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

NCT04029636 | Unknown

• 1 other identifier: 5996
• Study Type: observational
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Bronchiolitis Obliterans

Outcome Measures

Primary Outcomes (8)

• The change detected in Ventilation Defect Percent (VDP) on 129Xe MRI imaging in cross-sectional and prospectively followed cohorts.

  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.

  MRIs will be performed every three months for one year.

• The change detected in Apparent Diffusion Coefficients (ADC) on 129Xe MRI imaging in cross-sectional and prospectively followed cohorts.

  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.

  MRIs will be performed every three months for one year.

• The change detected in Signal-to-noice Ration (SNR) on 129Xe MRI imaging in cross-sectional and prospectively followed cohorts.

  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.

  MRIs will be performed every three months for one year.

• 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.

  FVC, FEV1, TLC, and RV will be documented in litres (L) through pulmonary function testing.

  Pulmonary Function Tests (PFTs) will be performed as clinically indicated, which in this study population will be every three months for two years.

• The change detected in FEV1/FVC ratio and RV/TLC ratio in cross-sectional and prospectively followed cohorts.

  FEV1/FVC ratio and RV/TLC ratio will be documented; these are ratios therefore and therefore do not have units.

  PFTs will be performed as clinically indicated, which in this study population will be every three months for two years.

• 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.

  Diffusion capacity of the lung for carbon monoxide (DLCO) and DLCO corrected for hemoglobin will be recorded in L/min/mmHg.

  PFTs will be performed as clinically indicated, which in this study population will be every three months for two years.

• 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.

  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

  PFTs will be performed as clinically indicated, which in this study population will be every three months for two years.

• The change detected in forced oscillometry technique (FOT) in cross-sectional and prospectively followed cohorts.

  Results recorded in hertz (Hz)

  Oscillometry will be recorded every three months for one year.

Secondary Outcomes (3)

• Change in airway resistance and reactance over time quantified by FOT

  Oscillometry will be recorded every three months for one year.

• Development of Bronchiolitis Obliterans Syndrome (BOS)

  Development of BOS will be documented over the study's duration (2 years).

• Development of clinical outcomes of death, hospitalization for respiratory cause, or respiratory failure.

  Outcomes will be documented over the study's duration (2 years).

Study Arms (2)

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

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

Interventions

Inhaled Hyperpolarized Xenon-129 OTHER

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

Established LONIPC; Trajectory of LONIPC

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hamilton Health Sciences Corporation: lead

Study Sites (1)

Hamilton Health Sciences

Hamilton, Ontario, L8V 1C3, Canada

Location

Related Publications (4)

• Chien JW, Duncan S, Williams KM, Pavletic SZ. Bronchiolitis obliterans syndrome after allogeneic hematopoietic stem cell transplantation-an increasingly recognized manifestation of chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2010 Jan;16(1 Suppl):S106-14. doi: 10.1016/j.bbmt.2009.11.002. Epub 2009 Nov 5.

  PMID: 19896545 BACKGROUND

• Walkup LL, Myers K, El-Bietar J, Nelson A, Willmering MM, Grimley M, Davies SM, Towe C, Woods JC. Xenon-129 MRI detects ventilation deficits in paediatric stem cell transplant patients unable to perform spirometry. Eur Respir J. 2019 May 2;53(5):1801779. doi: 10.1183/13993003.01779-2018. Print 2019 May.

  PMID: 30846475 BACKGROUND

• Kirby M, Heydarian M, Svenningsen S, Wheatley A, McCormack DG, Etemad-Rezai R, Parraga G. Hyperpolarized 3He magnetic resonance functional imaging semiautomated segmentation. Acad Radiol. 2012 Feb;19(2):141-52. doi: 10.1016/j.acra.2011.10.007. Epub 2011 Nov 21.

  PMID: 22104288 BACKGROUND

• Kirby M, Svenningsen S, Kanhere N, Owrangi A, Wheatley A, Coxson HO, Santyr GE, Paterson NA, McCormack DG, Parraga G. Pulmonary ventilation visualized using hyperpolarized helium-3 and xenon-129 magnetic resonance imaging: differences in COPD and relationship to emphysema. J Appl Physiol (1985). 2013 Mar 15;114(6):707-15. doi: 10.1152/japplphysiol.01206.2012. Epub 2012 Dec 13.

  PMID: 23239874 BACKGROUND

MeSH Terms

Conditions

Bronchiolitis Obliterans

Condition Hierarchy (Ancestors)

Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases

Central Study Contacts

Jane Turner, MD

CONTACT

905-906-2629; jane.turner@medportal.ca

Sarah Svenningsen, PhD

CONTACT

905-522-1155; svennins@mcmaster.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 7, 2019
• First Posted: July 23, 2019
• Study Start: August 1, 2019
• Primary Completion: August 1, 2021
• Study Completion: November 1, 2021
• Last Updated: July 23, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)