Non-contrast Lung Perfusion Mapping Applied for New Insights in Cystic Fibrosis

NCT04467957 | Active Not Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 2019-1192
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Cystic fibrosis (CF) results in the thickening of mucus in the lungs and other organs due to dysfunction of a transmembrane conductance protein. This allows buildup of bacteria that results in inflammation, leading to tissue breakdown and loss of function. In the lungs, this process causes loss of air exchange structures progressing to diminished lung function. The exchange of oxygen in the lungs depends on both the integrity of air conduits and vasculature. Most clinical assessments, however, focus on ventilatory function, with the assumption that any vascular compromise is secondary. Nevertheless, there is evidence, some from the investigator's lab, to suggest that perfusion anomalies in the lung occur before signs of ventilatory dysfunction. Thus, the inflammatory processes of CF may impact pulmonary microvasculature specifically and concurrently or prior to damage to ventilatory structures. This study aims to apply a new MRI method to serially measure regional lung perfusion, without the use of contrast agent, in children with CF and to associate it with regional assessments of ventilation and to serum cytokines or proteomic markers of angiogenesis and inflammatory processes. The investigator's lab has recently developed a noninvasive, non-contrast, method of labeling blood flowing into the lungs and generating a map of perfusion. The investigator aims to couple this technique to existing methods using hyperpolarized Xenon to map ventilation. The investigator will apply these methods over time in CF patients, monitoring the relationship between regional perfusion and ventilation defects. This pilot work will provide the foundation for larger studies to establish the essential etiological role of perfusion deficits in CF.

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis; Cystic fibrosis transmembrane conductance regulator modulator therapy; hyperpolarized xenon; Cystic fibrosis transmembrane conductance regulator (CFTR)

Outcome Measures

Primary Outcomes (4)

• Ventilation Defect Percentage (VDP)

  Lung defect calculations (total and lobar defect percentages) will be performed by evaluating the percentage of voxels with signals below a threshold value of 60% of the total lung mean signal. This threshold (60%) represents our estimate of the visually accurate defect selection threshold for CF patients. To assign the pixels in the hyperpolarized Xenon gas (129Xe) MRI slices to a lobe, corresponding CT and/or UTE MRI images will be segmented and analyzed with custom MATLAB software. VDP for CF and Control groups will be compared by 2-sample T-test at baseline. VDP at baseline and 6 months for the CF group will be compared by paired T-test to determine if the change is significantly different from zero change.

  Baseline and 6 months post Trikafta initiation for CF group. Baseline for CF and control groups.

• Perfusion Defect Percentage (PDP)

  Similar to the VDP, total and lobar defect percentages will be calculated for lung perfusion. As for VDP, PDP will be compared between CF and Control groups at baseline via 2-sample T-test. PDP change from baseline to 6 months will be measured for the CF group via paired T-test to determine change significantly different from zero change.

  Baseline and 6 months post Trikafta initiation for CF group. Baseline for CF and control groups.

• Degree of concordance between ventilation and perfusion defects

  Degree of concordance between ventilation and perfusion defects will be calculated as percentage of overlap between ventilation and perfusion defect volumes.

  Baseline and 6 months post Trikafta initiation for CF group. Baseline for CF and control groups.

• Proteome assays as global indicators of inflammatory/angiogenic processes

  Proteome assays as global indicators of inflammatory/angiogenic processes, will be compared between groups by 2-sample T-test. Correlation analyses will be performed to examine associations between quantitative image scores for each modality (VDP and PDP) and lung function (FEV1%), as well as proteome concentrations.

  Baseline and 6 months post Trikafta initiation for CF group. Baseline for CF and control groups.

Study Arms (2)

CF Cohort

EXPERIMENTAL

16 Cystic Fibrosis Patients will undergo MRI imaging before and 6 months after initiation of triple-combination modulator therapy. Initiation of triple -combination modulator therapy will be determined by clinician and family prior to study enrollment. Hyperpolarized Xenon 129 will be administered through inhalation at two MRI imaging study visits.

Drug: Initiation of CFTR Modulator; Drug: Hyperpolarized Xenon 129

Control Cohort

EXPERIMENTAL

10 Healthy control study participants matched for age and gender will undergo one MRI imaging study visit. Hyperpolarized Xenon 129 will be administered through inhalation at one MRI imaging study visit.

Drug: Hyperpolarized Xenon 129

Interventions

Initiation of CFTR Modulator DRUG

Inhaled contrast for MRI occurring at each visit

Also known as: 129Xe

CF Cohort

Hyperpolarized Xenon 129 DRUG

Inhaled contrast for MRI occurring at each visit

Also known as: 129Xe

CF Cohort; Control Cohort

Eligibility Criteria

• Age: 6 Years - 21 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• male or female between the ages of 6 through 21 years
• diagnosis of CF by positive sweat test and genetic test
• planning to start Trikafta based on clinical decision
• baseline pulmonary function test (PFT) defined as FEV1% that is no less than 5% of the best PFT in the previous 6 months
• Absence of exacerbation defined as
• No acute antibiotic usage for 14 days prior to MRI visit
• Able to perform an acceptable and reproducible spirometry
• O2 saturation level at 90% or greater when laying flat
• male or female between the ages of 6 through 21 years
• no known diagnoses that impact lung function in the opinion of the investigators

You may not qualify if:

• pregnancy

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Officials

• Mark DiFrancesco, PhD

  CCHMC

  PRINCIPAL INVESTIGATOR

• Jason Woods, PhD

  CCHMC

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2020
• First Posted: July 13, 2020
• Study Start: November 15, 2020
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)