Imaging Biomarkers for Cystic Fibrosis
(BEGINNING Trial)
Recruiting in Palo Alto (17 mi)
+3 other locations
Overseen byJason Woods, PhD
Age: < 18
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
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
Prior Safety Data
Breakthrough Therapy
Approved in 1 Jurisdiction
Trial Summary
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.
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.12345
Is hyperpolarized 129Xe MRI safe for use in humans, particularly children with cystic fibrosis?
How is the treatment 129Xe unique for cystic fibrosis?
Eligibility Criteria
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.
See 7 more
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.
See 6 more
Trial Timeline
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)
Treatment Details
Interventions
- 129Xe (Gas)
Trial OverviewThe 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.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Pre TrikaftaExperimental Treatment1 Intervention
129Xe MRI
Group II: Post TrikaftaExperimental Treatment1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Cincinnati Children's Hospital Medical CenterCincinnati, OH
University of VirginiaCharlottesville, VA
University of Kansas Medical CenterKansas City, KS
Carrie StevensCincinnati, OH
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Who Is Running the Clinical Trial?
Children's Hospital Medical Center, CincinnatiLead Sponsor
University of VirginiaCollaborator
University of KansasCollaborator
University of IowaCollaborator
References
Hyperpolarized 129Xe for investigation of mild cystic fibrosis lung disease in pediatric patients. [2022]Label="BACKGROUND" NlmCategory="BACKGROUND">Cystic fibrosis (CF) is a genetic disease which carries high morbidity and mortality from lung-function decline. Monitoring disease progression and treatment response in young patients is desirable, but serial imaging via CT is often considered prohibitive, and detailed functional information cannot be obtained using conventional imaging techniques. Hyperpolarized 129Xe magnetic resonance imaging (MRI) can depict and quantify regional ventilation, but has not been investigated in pediatrics. We hypothesized that 129Xe MRI is feasible and would demonstrate ventilation defects in mild CF lung disease with greater sensitivity than FEV1.
Comparison of single breath hyperpolarized 129 Xe MRI with dynamic 19 F MRI in cystic fibrosis lung disease. [2021]Label="PURPOSE">To quantitatively compare dynamic 19 F and single breath hyperpolarized 129 Xe MRI for the detection of ventilation abnormalities in subjects with mild cystic fibrosis (CF) lung disease.
Novel imaging techniques for cystic fibrosis lung disease. [2022]With an increasing number of patients with cystic fibrosis (CF) receiving highly effective CFTR (cystic fibrosis transmembrane regulator protein) modulator therapy, particularly at a young age, there is an increasing need to identify imaging tools that can detect and regionally visualize mild CF lung disease and subtle changes in disease state. In this review, we discuss the latest developments in imaging modalities for both structural and functional imaging of the lung available to CF clinicians and researchers, from the widely available, clinically utilized imaging methods for assessing CF lung disease-chest radiography and computed tomography-to newer techniques poised to become the next phase of clinical tools-structural/functional proton and hyperpolarized gas magnetic resonance imaging (MRI). Finally, we provide a brief discussion of several newer lung imaging techniques that are currently available only in selected research settings, including chest tomosynthesis, and fluorinated gas MRI. We provide an update on the clinical and/or research status of each technique, with a focus on sensitivity, early disease detection, and possibilities for monitoring treatment efficacy.
The assessment of short and long term changes in lung function in CF using 129Xe MRI. [2022]Label="INTRODUCTION" NlmCategory="BACKGROUND"> 129Xe ventilation MRI is sensitive to detect early CF lung disease and response to treatment. 129Xe-MRI could play a significant role in clinical trials and patient management. Here we present data on the repeatability of imaging measurements and their sensitivity to longitudinal change.
Hyperpolarised 129Xe magnetic resonance imaging to monitor treatment response in children with cystic fibrosis. [2020]Pulmonary magnetic resonance imaging using hyperpolarised 129Xe gas (XeMRI) can quantify ventilation inhomogeneity by measuring the percentage of unventilated lung volume (ventilation defect per cent (VDP)). While previous studies have demonstrated its sensitivity for detecting early cystic fibrosis (CF) lung disease, the utility of XeMRI to monitor response to therapy in CF is unknown. The aim of this study was to assess the ability of XeMRI to capture treatment response in paediatric CF patients undergoing inpatient antibiotic treatment for a pulmonary exacerbation.15 CF patients aged 8-18 years underwent XeMRI, spirometry, plethysmography and multiple-breath nitrogen washout at the beginning and end of inpatient treatment of a pulmonary exacerbation. VDP was calculated from XeMRI images obtained during a static breath hold using semi-automated k-means clustering and linear binning approaches.XeMRI was well tolerated. VDP, lung clearance index and the forced expiratory volume in 1 s all improved with treatment; however, response was not uniform in individual patients. Of all outcome measures, VDP showed the largest relative improvement (-42.1%, 95% CI -52.1--31.9%, p<0.0001).These data support further investigation of XeMRI as a tool to capture treatment response in CF lung disease.
Feasibility, tolerability and safety of pediatric hyperpolarized 129Xe magnetic resonance imaging in healthy volunteers and children with cystic fibrosis. [2022]Label="BACKGROUND" NlmCategory="BACKGROUND">Hyperpolarized 129Xe is a promising contrast agent for MRI of pediatric lung function, but its safety and tolerability in children have not been rigorously assessed.
Estimation of the radiation dose from thoracic CT scans in a cystic fibrosis population. [2016]To determine the radiation exposure associated with CT scans in a population of patients with cystic fibrosis (CF).
[A critical study of technetium 99m and xenon 133 lung scintigraphy in patients with cystic fibrosis]. [2016]During investigations for cystic fibrosis, 41 children, most of whom were aged 0 to 7 years, were submitted to lung scintigraphy with technetium 99m first and xenon 133 subsequently. This procedure ensured accurate location of pulmonary lesions. The reliability of the radio-isotopic study was assessed through comparison to conventional clinical and radiological criteria, arterial blood gas determinations and pulmonary function tests. Perfusion scintigraphy with technetium 99m labelled macroaggregated albumin (n = 90) was compared to functional parametrical xenon, 133 study (n = 25) (perfusion-ventilation). The degree of lung disease was evaluated during serial examinations in order to improve prognostic prediction. Technetium 99m scintigraphy proves a reliable and sensitive procedure which accurately reflects the patients' clinical status when it is performed in the absence of patent pulmonary superinfection. Xenon 133 scintigraphy, which is more difficult to perform and interpret, has the advantage of providing a topographic and quantitative evaluation of pulmonary blood flow and ventilatory efficiency.
Intra- and Inter-visit Repeatability of 129 Xenon Multiple-Breath Washout MRI in Children With Stable Cystic Fibrosis Lung Disease. [2023]Label="BACKGROUND">Multiple-breath washout (MBW) 129 Xe MRI (MBW Xe-MRI) is a promising technique for following pediatric cystic fibrosis (CF) lung disease progression. However, its repeatability in stable CF needs to be established to use it as an outcome measure for novel therapies.