Clinical trial NCT06339593: Regional Monitoring of CF Lung Disease
Official title: Regional Monitoring of CF Lung Disease After Changes in Mechanical Airway-clearance Treatment
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cystic Fibrosis
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
First posted: 2024-04-01
Enrollment: 80
Sex: ALL
Minimum age (years): 12
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: We will recruit approximately 75 Cystic Fibrosis patients between the ages 12-21.

Brief summary: The main reason for this research study is to learn more about some new tests that are being developing for patients with Cystic Fibrosis (CF) to measure changes in the lungs. In this study, the focus will be to learn how stopping Airway Clearance (ACT) and re-starting ACT can affect these tests. These new tests include using a breathable gas called Xenon (Xe) with MRI (magnetic resonance imaging) to improve the pictures of changes in the lungs. The Xenon (Xe) gas that has been treated to have a larger MRI signal (also called hyperpolarized). The other new test is called LCI (Lung Clearance Index) that can measure how well the lungs are working. The MRI machine used in this study has been approved by the U.S. Food and Drug Administration (FDA) and is commercially available for sale in the USA. Hyperpolarized Xe gas is an FDA-approved, inhaled contrast agent for lung ventilation MRI. The new Xe MRI techniques that are being developed and used for this research study are investigational, meaning these new Xe MRI techniques are not FDA approved, but they are similar to FDA-approved techniques that are used clinically at Cincinnati Children's Hospital Medical Center (CCHMC). Xe gas and the new MRI techniques used in this research study have been used for many years in research, including in many research studies conducted at CCHMC like this one.

Detailed description: Cystic fibrosis (CF) is a progressive, systemic disease affecting an estimated 30,000 children and adults in the United States (70,000+ worldwide) and is caused by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) protein--a chloride and bicarbonate channel that regulates ion transport and mucus composition in CF-affected tissues, such as the lung. In airways this leads to mucus stasis, infection, inflammation, and remodeling that result in mucus plugs, regional lung obstruction, and progressive airway destruction and bronchiectasis. Highly-effective CFTR modulators, which are recently available to \>90% of patients, have revolutionized CF clinical care, with large increases in pulmonary function as a result of more effective mucociliary clearance. As a result, burdensome maintenance therapies like mechanical airway clearance treatment (ACT), requiring nearly 2 dedicated hours per day, have been questioned by patients, families, and medical providers. In a recent survey of CF community members, ACT was ranked as the most burdensome chronic therapy, yet is the least studied. Prospective studies of maintenance-therapy withdrawal pose potential ethical risks, since traditional testing via spirometry and/or multiple-breath washout is relatively insensitive to small or regional changes and long-term lung-function reductions often have permanent consequences. Nevertheless, many patients have withdrawn these maintenance therapies against advice from their providers. A major gap in CF management is our ability to monitor lung function sensitively and rapidly as a result of treatment changes, such as partial withdrawal of ACT.

Breakthroughs in structural and functional magnetic resonance imaging (MRI) have demonstrated exquisite sensitivity to regional CF lung disease and can monitor regional and subtle changes over time, without ionizing radiation, even in patients with normal spirometry. As demonstrated in the previous R01 that ultrashort echo time (UTE) MRI provides structural images that rival computered tomography (CT) imaging, with sensitivity to detect all of the structural hallmarks of treatable (e.g., mucus plugs) and permanent lung disease (e.g., bronchiectasis). It has been demonstrated that hyperpolarized 129Xe MRI is more sensitive than any other technique at detecting changes in regional pulmonary ventilation and gas exchange. For the first time, a single modality (MRI) is available to safely monitor regional lung disease and treatment changes before FEV1 declines become permanent. This is a unique opportunity to safely evaluate ACT in CF populations that remain at risk of long-term lung function decline.

Eligibility criteria: Inclusion Criteria:

* 1 Written informed consent (and assent when applicable) obtained from subject or subject's legal representative.

  2 Use of highly effective modulators for more than 30 days (ie. Trikafta) 3 Willingness and ability to adhere to the study visit schedule and other protocol requirements.

  4 Documentation of a CF diagnosis with prescription of Mechanical ACT 5 Ages 12-21 inclusive, at the time of consent. 6 Clinically stable with no respiratory tract infection or recent exacerbations. 7 Treating CF physician agreeable to study procedures. Only applicable to Aim 3.

  8 No change in chronic maintenance therapies in the 28 days prior to enrollment.

  9 Ability to cooperate with MRI procedures.

Exclusion Criteria:

1. Standard MRI exclusions (metal implants, claustrophobia).
2. For females of childbearing potential: Positive urine pregnancy test or Lactating.
3. Acute respiratory symptoms (e.g., wheezing) at the time of the MRI
4. Chronic lung or liver or pancreatic disease not related to CF.
5. Any other condition that, in the opinion of the Investigator, would preclude informed consent or assent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.

Primary outcomes:
measure: Assessing structural and functional lung abnormalities via Xenon MRI
timeFrame: two weeks
Secondary outcomes:
measure: Assessing patients who have self-withdrawn airway clearance treatment to determine ventilation abnormalities.
timeFrame: two weeks
Other outcomes:
measure: Change in Xenon Ventilation Defect Process (VDP)
timeFrame: 4 weeks
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
Study officials:
affiliation: Cincinnati Children's Hospital Medica Center
name: Jason C Woods, PhD
role: PRINCIPAL_INVESTIGATOR
References: