Regional Monitoring of CF Lung Disease

Cystic Fibrosis Clinical Trial

Official title:

Regional Monitoring of CF Lung Disease After Changes in Mechanical Airway-clearance Treatment

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06339593
• Other study ID #: 2023-0391
• Status: Recruiting
• Start date: January 5, 2024
• Est. completion date: January 2028

Study information

• Verified date: March 2024
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: Carrie Stevens, BS
• Phone: (513) 636-9973
• Email: carrie.stevens[@]cchmc.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: January 2028
• Est. primary completion date: January 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 21 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Lung Diseases

Intervention

Drug:
• Hyperpolarized Xe129
Hyperpolarized Xe MRI is FDA Approved for Adults and Children 12 and above We have been performing Xe MRI for research in human subjects for over 20 years, and for over 10 years at CCHMC. Recent FDA approval of hyperpolarized Xe MRI for ventilation stands as a testament to its safety and value as a modern tool for exploring lung disease and function. Earlier studies using Xe MRI have shown its efficacy in exploring CF and other lung diseases in pediatric and adult populations, and it has been found to be much more sensitive to early lung disease than traditional metrics like spirometry and MBW

Locations

Country	Name	City	State
United States	Cincinnati Children's Hospital	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Xenon Ventilation Defect Process (VDP)	Examine the lung function decline of patients after airway clearance techniques (ACT) withdrawal. The baseline visit will be measured with UTE and Xenon MRI, Spirometry and lung clearance Index (LCI) and compared to Visit 2 and Visit 3 through non-parametric tests specifically the Wilxcoxon signed-rank test.	4 weeks
Primary	Assessing structural and functional lung abnormalities via Xenon MRI	We will perform UTE and hyperpolarized Xenon MRIs in patients in with Cystic Fibrosis. We will correlate regional structural lung abnormalities via UTE Floret MRI to functional deficits via Xenon MRI.	two weeks
Secondary	Assessing patients who have self-withdrawn airway clearance treatment to determine ventilation abnormalities.	We will be using UTE and Xenon MRI, spirometry, and multiple-breath washout at the baseline visit. We plan to increase treatment	two weeks