Imaging Biomarkers for Cystic Fibrosis

(BEGINNING Trial)

Recruiting at 3 trial locations

Overseen By Penny New, BS

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: Children's Hospital Medical Center, Cincinnati

Must be taking: Triple-combination therapy

Must not be taking: Ivacaftor

Disqualifiers: Acute respiratory symptoms, Chronic lung disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

44 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial studies a new treatment option for young children with cystic fibrosis, a genetic condition affecting the lungs and digestive system. Researchers examine the effects of a triple-combination therapy using a special type of MRI scan with 129Xe (also known as Xenon Xe-129 or Xenoview) to observe changes in the lungs and abdomen. The trial includes two groups: those who haven't started the therapy and those who have. Eligible children are between 6 and 8 years old, have a confirmed diagnosis of cystic fibrosis, and are set to begin this new therapy. As a Phase 4 trial, this research aims to understand how the already FDA-approved and proven effective treatment benefits more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not have changed your chronic maintenance therapies in the 28 days before joining. If you are on ivacaftor therapy with certain mutations, you cannot participate.

What is the safety track record for 129Xe?

Research has shown that hyperpolarized 129Xe in MRI scans is safe and well-tolerated for children. Studies have found this inhaled contrast agent effective for lung imaging in kids, including those with cystic fibrosis. The FDA has approved its use for children aged 6 and older, confirming its safety for this age group. No reports of serious side effects exist, and it does not expose patients to radiation, making it a safer option compared to some other imaging methods. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about this trial because it explores the use of 129Xe MRI as a novel imaging biomarker for cystic fibrosis. Unlike traditional lung function tests and CT scans, which can be limited in detecting early changes in lung tissue, 129Xe MRI provides a unique way to visualize gas exchange in the lungs at a detailed level. This technique could offer new insights into how treatments like Trikafta impact lung function over time, potentially leading to more personalized and effective management of cystic fibrosis.

What evidence suggests that this trial's treatments could be effective for cystic fibrosis?

Research has shown that Xenon Xe-129 MRI effectively tracks lung disease progression in people with cystic fibrosis. This trial will use Xenon Xe-129 MRI both before and after Trikafta treatment to assess its effectiveness in detecting changes in lung function and structure. This imaging method identifies changes in lung function and appearance, aiding in predicting future flare-ups. Studies have found that it can detect mild lung disease and monitor lung function in children with cystic fibrosis. It provides quick and accurate results, crucial for managing and understanding the disease. Overall, Xenon Xe-129 MRI serves as a powerful tool for assessing lung health in cystic fibrosis. ^{6 7 8 9 10}

Who Is on the Research Team?

Jason Woods, PhD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Are You a Good Fit for This Trial?

This trial is for children aged 6-8 with Cystic Fibrosis, who have high sweat chloride levels and two specific CFTR gene mutations. They must be able to undergo MRI scans, be clinically stable without recent respiratory infections or changes in maintenance therapies. Kids on ivacaftor therapy or with certain mutations can't join.

Inclusion Criteria

My doctor plans to treat me with a three-drug combination.

I have been diagnosed with cystic fibrosis based on symptoms and tests.

I do not have a lung infection and my condition is stable.

Exclusion Criteria

I am experiencing wheezing or similar symptoms currently.

I have a long-term pancreatic condition not caused by cystic fibrosis.

I have had symptoms like coughing or wheezing in the last 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre Trikafta Treatment

Participants undergo 129Xe MRI to establish baseline measurements before starting triple-combination therapy

4 weeks

1 visit (in-person)

Post Trikafta Treatment

Participants receive triple-combination therapy and undergo 129Xe MRI to assess treatment effects

48 weeks

4 visits (in-person)

Follow-up

Participants are monitored for changes in ventilation defect percentage, pancreas volume, and other MRI measures

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• 129Xe

Trial Overview

The study tests the effects of a triple-combination therapy using advanced MRI techniques (UTE and 129Xe) after its expected approval by the FDA. It aims to assess how this treatment impacts lung and abdominal health in young patients.

How Is the Trial Designed?

Group I: Pre Trikafta Experimental Treatment 1 Intervention

129Xe MRI

Group II: Post Trikafta Experimental Treatment 1 Intervention

129Xe MRI

129Xe is already approved in United States for the following indications:

Approved in United States as Xenoview for:

• Evaluation of lung ventilation in adults and pediatric patients aged 12 years and older

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

University of Virginia

Collaborator

Trials

802

Recruited

1,342,000+

University of Kansas

Collaborator

Trials

157

Recruited

332,000+

University of Iowa

Collaborator

Trials

486

Recruited

934,000+

Published Research Related to This Trial

Technetium 99m scintigraphy is a reliable and sensitive method for accurately assessing lung conditions in children with cystic fibrosis, especially when there is no active lung infection.

Xenon 133 scintigraphy, while more complex, offers valuable topographic and quantitative insights into pulmonary blood flow and ventilation efficiency, complementing the findings from technetium 99m studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A critical study of technetium 99m and xenon 133 lung scintigraphy in patients with cystic fibrosis]. Loeuille, GA., Steinling, M., Dubois, P., et al.[2016]

As more patients with cystic fibrosis (CF) receive effective CFTR modulator therapy, there is a growing need for advanced imaging tools to detect early lung disease and monitor subtle changes in condition.

This review highlights both traditional imaging methods like chest radiography and CT scans, as well as emerging techniques such as proton and hyperpolarized gas MRI, which may enhance early disease detection and treatment monitoring in CF patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel imaging techniques for cystic fibrosis lung disease. Goralski, JL., Stewart, NJ., Woods, JC.[2022]

Patients with cystic fibrosis (CF) received a mean effective dose (ED) of 6.5 mSv per thoracic CT scan, with a lifetime average of 19.5 mSv per patient, indicating significant radiation exposure that requires careful monitoring.

The age at which patients received their first CT scan has decreased significantly over the years, from an average of 20 years for those born before 1980 to just 1.9 years for those born after 1997, highlighting a trend towards earlier imaging in CF management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estimation of the radiation dose from thoracic CT scans in a cystic fibrosis population. Donadieu, J., Roudier, C., Saguintaah, M., et al.[2016]

In a study involving 10 participants with mild cystic fibrosis, both dynamic 19F and hyperpolarized 129Xe MRI effectively detected ventilation abnormalities, but they provided different insights into lung function.

The results showed that while both imaging techniques identified ventilation defects, they were not entirely congruent, indicating that using both methods together can give a more comprehensive view of lung ventilation status in cystic fibrosis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of single breath hyperpolarized 129 Xe MRI with dynamic 19 F MRI in cystic fibrosis lung disease. McCallister, A., Chung, SH., Antonacci, M., et al.[2021]

Pulmonary magnetic resonance imaging using hyperpolarised 129Xe gas (XeMRI) was well tolerated in 15 pediatric cystic fibrosis patients and showed a significant improvement in ventilation defect percentage (VDP) by 42.1% after antibiotic treatment for a pulmonary exacerbation.

XeMRI effectively captured treatment response, indicating its potential as a valuable tool for monitoring lung function in cystic fibrosis, alongside traditional measures like spirometry and lung clearance index.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarised 129Xe magnetic resonance imaging to monitor treatment response in children with cystic fibrosis. Rayment, JH., Couch, MJ., McDonald, N., et al.[2020]

Hyperpolarized 129Xe MRI can effectively detect ventilation defects in pediatric patients with mild cystic fibrosis (CF), even when traditional measures like FEV1 show normal results, indicating its potential as a sensitive diagnostic tool.

In a study of 22 participants (11 healthy controls and 11 CF patients), the ventilation defect percentage (VDP) was significantly higher in CF patients (18.3%) compared to controls (6.4%), suggesting that 129Xe MRI may be a valuable method for monitoring lung function and disease progression in young CF patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized 129Xe for investigation of mild cystic fibrosis lung disease in pediatric patients. Thomen, RP., Walkup, LL., Roach, DJ., et al.[2022]

The study demonstrated that multiple-breath washout (MBW) 129 Xe MRI has high repeatability for both intravisit and intervisit assessments in healthy children and those with stable cystic fibrosis, indicating its potential as a reliable outcome measure for monitoring lung disease progression.

The coefficient of variation of fractional ventilation (CoVFV) from MBW Xe-MRI showed a significant correlation with lung clearance index (LCI), highlighting the importance of assessing ventilation heterogeneity in early cystic fibrosis lung disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intra- and Inter-visit Repeatability of 129 Xenon Multiple-Breath Washout MRI in Children With Stable Cystic Fibrosis Lung Disease. Alam, FS., Zanette, B., Munidasa, S., et al.[2023]

Hyperpolarized 129Xe gas is safe and well-tolerated as an inhaled contrast agent for MRI in children, with no serious adverse events reported during the study involving 28 participants aged 6 to 16 years.

While some children experienced mild and temporary changes in oxygen saturation and heart rate after inhalation, these effects were consistent with expected physiological responses and resolved quickly, indicating that 129Xe MRI is feasible for assessing lung function in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility, tolerability and safety of pediatric hyperpolarized 129Xe magnetic resonance imaging in healthy volunteers and children with cystic fibrosis. Walkup, LL., Thomen, RP., Akinyi, TG., et al.[2022]

Xenon-129 (129Xe) MRI is a reliable imaging technique for assessing lung disease in cystic fibrosis (CF) patients, showing high repeatability in measurements of ventilation defect percentage (VDP) over time.

In a study of 29 CF patients, significant changes in VDP were observed even when forced expiratory volume (FEV1) remained stable, indicating that 129Xe-MRI can detect early lung function changes that traditional measures may miss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The assessment of short and long term changes in lung function in CF using 129Xe MRI. Smith, LJ., Horsley, A., Bray, J., et al.[2022]

Citations

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Imaging Biomarkers for Cystic Fibrosis (BEGINNING Trial)

What data supports the effectiveness of the treatment Xenon Xe-129 for cystic fibrosis? Research shows that using Xenon Xe-129 in MRI scans can effectively ...

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Additionally, 129XeMRI is effective in determining disease progression and bronchial abnormalities linked to future pulmonary exacerbations, with similar VDPs ...

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Faster and more accurate xenon 129 ventilation MRI was achieved in individuals with cystic fibrosis by combining two-dimensional spiral ...

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129 Xe may be a useful outcome measure to detect mild CF lung disease, to investigate regional lung function in pediatric lung diseases, and to follow disease ...

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and long-term changes in lung function in cystic fibrosis using ...

129 Xe-MRI is a highly effective method for assessing longitudinal lung disease in patients with CF. VDP has great potential as a sensitive clinical outcome ...

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The safety and effectiveness of XENOVIEW have been established in pediatric patients aged 6 years and older for use with MRI to evaluate lung ventilation. Use ...

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The FDA has expanded the approval of Xenoview (xenon Xe 129 hyperpolarized) to include use in pediatric patients aged 6 years and older.

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accessdata.fda.gov/drugsatfda_docs/label/2022/214375s000lbl.pdf

XENOVIEW (xenon Xe 129 hyperpolarized), for oral inhalation

The safety and effectiveness of XENOVIEW have been established in pediatric patients aged 12 years and older for use with MRI to evaluate lung ventilation. Use ...

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5083137/

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Data submitted to the FDA compared images HP Xe 129 MR images to Xenon ... HP Xe 129 safety profile does not expose the patient to radioactivity unlike Xenon 133.