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?

To determine the treatment effect of triple-combination therapy in 6-8 year olds after presumed FDA approval, using rapid structural and functional pulmonary and abdominal MRI (UTE and 129Xe).

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.

Is hyperpolarized 129Xe MRI safe for use in humans, particularly children with cystic fibrosis?

Research indicates that hyperpolarized 129Xe MRI is being studied for its safety and tolerability in children, including those with cystic fibrosis, but detailed safety assessments are still ongoing. ^{1 2 3 4 5}

How is the treatment 129Xe unique for cystic fibrosis?

The treatment 129Xe is unique for cystic fibrosis because it uses hyperpolarized xenon gas in MRI scans to provide detailed images of lung ventilation, allowing for early detection and monitoring of lung disease progression, which is more sensitive than traditional methods. ^{2 4 6 7 8}

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 detect early lung disease in cystic fibrosis patients and monitor their response to treatment. This imaging technique is sensitive in identifying ventilation issues and has shown significant improvements in lung function measurements after treatment. ^{2 4 6 7 9}

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

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]

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]

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]

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]

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 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]

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]

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]

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]

Citations

1. Netherlands pubmed.ncbi.nlm.nih.gov

Hyperpolarized 129Xe for investigation of mild cystic fibrosis lung disease in pediatric patients. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Comparison of single breath hyperpolarized 129 Xe MRI with dynamic 19 F MRI in cystic fibrosis lung disease. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Novel imaging techniques for cystic fibrosis lung disease. [2022]

4. England pubmed.ncbi.nlm.nih.gov

The assessment of short and long term changes in lung function in CF using 129Xe MRI. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Hyperpolarised 129Xe magnetic resonance imaging to monitor treatment response in children with cystic fibrosis. [2020]

6. Germany pubmed.ncbi.nlm.nih.gov

Feasibility, tolerability and safety of pediatric hyperpolarized 129Xe magnetic resonance imaging in healthy volunteers and children with cystic fibrosis. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Estimation of the radiation dose from thoracic CT scans in a cystic fibrosis population. [2016]

8. France pubmed.ncbi.nlm.nih.gov

[A critical study of technetium 99m and xenon 133 lung scintigraphy in patients with cystic fibrosis]. [2016]

9. United States 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. [2023]