Hp129 Xenon Imaging and BOS in Lung Transplantation

This protocol aims to

* Develop new imaging methods that are sufficiently sensitive to allow early diagnosis of BOS.
* Improve patient treatment outcomes through earlier diagnosis of changes leading to BOS by obtaining image guided biopsies of transplanted lung.
* Provide image guided biopsies for use in future research of ex vivo biomarkers of BOS and in the development of treatments through future clinical trials.

The study will achieve these aims through a prospective, non-randomized, longitudinal, observational study that will recruit about 5 subjects a year for 5 years. The study will follow these post lung transplant patients at 6 months and 1 year with 129Xe MRI (Hyperpolarized 129Xenon Magnetic Resonance Imaging) and image guided bronchial biopsies to detect early BOS and to better understand BO disease progression. The biopsies will provide future research for rapid determination of cellular and molecular mechanisms that lead to BOS and to facilitate identification and validation of translatable pharmaceutical targets.

• Hp 129Xenon (Drug): 129 Xenon is a noble gas with no taste or smell. It will be made slightly magnetic (also called hyperpolarizing) and then inhaled into the lungs to provide better pictures of the lungs during MRI.

Primary outcomes

• Ventilation Defect Percentage (VDP) [6 months post transplant]: Capture HP 129Xe and 1H MR images for clinician review for regional ventilation defects in post-transplant BOS patients during routine clinical visits Images were obtained on the 3 participants enrolled in the study at the 6-month post-transplant timepoint. Ventilation Defect Percentage (VDP) was recorded for all 3 study participants. VDP outcomes are listed in the Outcome Measure Data Table.

Secondary outcomes

• Ventilation Defect Percentage (VDP) [12 months post transplant]: Capture HP 129Xe and 1H MR images for clinician review for regional ventilation defects in post-transplant BOS patients during routine clinical visits. Because this study was closed due to low enrollment and difficulty to recruit due to the age restrictions and limited patient population, images were not taken at the 12-month-post transplant timeframe.

Sex: All, ages: 6 Years to any

Inclusion Criteria:

* Lung Transplantation within the last 10 years or being assessed for possible lung transplantation.
* Participant must be able to hold their breath for up to 16 seconds.

Exclusion Criteria:

* Standard MRI exclusion criteria
* Bleeding disorders
* Participant is claustrophobic or otherwise unable to tolerate the imaging
* Pregnancy or positive pregnancy test
* Symptoms of respiratory infection within the past two weeks.
* Baseline oximetry at MRI visit of less than 95% on room air or less than 95% on a previously prescribed dosage of oxygen delivered by nasal cannula.

Participant flow

Outcome results

• Ventilation Defect Percentage (VDP) (Primary), Number, Ventilation Defect Percentage (VDP): Hp 129Xenon 33.3
• Ventilation Defect Percentage (VDP) (Secondary)

Adverse events

Time frame: AEs/SAEs were monitored up to 7 days after baseline MRI visit and up to 7 days after the 6-month MRI visit.

• Study Protocol and Statistical Analysis Plan (PDF, 2017-09-19)

• Jason Woods, PhD, Principal investigator, Children's Hospital Medical Center, Cincinnati