CFTR Modulator Therapy for Cystic Fibrosis
(HyPOINT Trial)
Trial Summary
What is the purpose of this trial?
The introduction of triple combination CFTR modulator therapy for patients with Cystic Fibrosis (CF) with at least one copy of the deltaF508 mutation is expected to provide major health benefits, but will also require novel outcome measures that can detect CF lung disease at an early stage, capture the efficacy of new therapies when disease manifestations are limited, as well as determine whether stopping existing chronic maintenance therapies does not have negative effects. In the past decade, research has focused on the multiple breath washout (MBW) test, as a sensitive outcome measure, especially if highly-effective modulator therapies are initiated in early childhood. Even LCI, however, may not adequately capture early lung function changes, thus warranting investigation of even more sensitive outcome measures. Magnetic resonance imaging (MRI) has the advantage of being a radiation-free modality, making it more suitable for assessing response to therapy in a shorter time frame with repeated imaging. Inhalation of a hyperpolarized gas enables the visualization and quantification of regional ventilation in the lung and can be combined with structural MRI to assess both structure and function in parallel. The main Investigator and others have recently formed an international consortium (the 129Xe MRI Clinical Trial Consortium), comprised of both imaging experts and pulmonary clinicians to standardize imaging procedures, thus facilitating multi-site implementations. Data from this proposed study (HyPOINT; Hyperpolarized Imaging for New Treatments) will inform the future utility of MRI for both longitudinal studies to track disease progression over time as well as for future interventional trials. Further, the current study could inform the design of future trials of interventions of patients for whom currently no effective CFTR modulator therapy is available and for patients with rare genotypes thus laying the groundwork for a more personalized medicine approach in the near-term future.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but it does require that there be no changes in your chronic pulmonary medications or therapies in the 28 days before the first visit. This suggests you should continue your current medications without changes before starting the trial.
What data supports the effectiveness of the treatment Hyperpolarized Imaging for Cystic Fibrosis?
Research shows that hyperpolarized MRI, using gases like helium-3 and xenon-129, can effectively detect ventilation defects in cystic fibrosis patients, providing detailed functional information that traditional imaging methods might miss. This imaging technique has been used to assess the response to CFTR modulator therapies, like ivacaftor, which have shown clinical benefits in improving lung function and mucus clearance in patients with specific genetic mutations.12345
Is CFTR modulator therapy safe for humans?
CFTR modulator therapies, used to treat cystic fibrosis, are generally well-tolerated but can have side effects. Real-world studies show that some people experience adverse events like respiratory issues, mental health changes, and liver problems, which may lead to stopping the treatment. It's important to monitor for these side effects, and healthcare providers, including pharmacists, play a key role in managing them.36789
How does the drug ivacaftor differ from other treatments for cystic fibrosis?
Ivacaftor is unique because it specifically targets the underlying cause of cystic fibrosis by improving the function of the defective CFTR protein, which helps to increase ion transport and reduce mucus viscosity in the lungs. This mechanism is different from other treatments that mainly address symptoms rather than the root cause of the disease.1341011
Research Team
Jason Woods, PhD
Principal Investigator
Children's Hospital Medical Center, Cincinnati
Eligibility Criteria
This trial is for people with Cystic Fibrosis who have at least one deltaF508 mutation. They must be able to follow the study schedule, give consent, and have been stable on certain CFTR modulators or not on any such therapy. Ages vary by phase: 6-18 for Phase 1 and 9-18 for Phase 2. Participants need normal organ function and no recent acute illness.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Phase 1: Baseline and Repeated 129Xe MRI Scanning
Implementation of a centralized analysis program of repeated 129Xe MRI scanning in CF patients with mild lung disease to define the intra-subject variability of the primary outcome ventilation defect percentage (VDP).
Phase 2: Observational Study with Triple-Combination Modulator Therapy
Patients assessed before and after the clinical initiation of triple-combination modulator therapy, with primary endpoint being the change of VDP after 28 days.
Follow-up
Participants are monitored for safety and effectiveness after treatment
Treatment Details
Interventions
- Hyperpolarized Imaging
Find a Clinic Near You
Who Is Running the Clinical Trial?
Children's Hospital Medical Center, Cincinnati
Lead Sponsor
University of Virginia
Collaborator
University of Wisconsin, Madison
Collaborator
The Hospital for Sick Children
Collaborator