BEGIN Novel ImagiNG Biomarkers

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified October 2024 by Children's Hospital Medical Center, Cincinnati
Sponsor
Children's Hospital Medical Center, Cincinnati
Information Provided by (Responsible Party)
Jason Woods
Clinicaltrials.gov Identifier
NCT05517655
Other Study ID Numbers:
2021-0325
First Submitted
April 5, 2022
First Posted
August 25, 2022
Last Update Posted
November 20, 2024
Last Verified
October 2024

ClinicalTrials.gov processed this data on November 2024. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

The overall hypothesis is that multi-organ MRI will provide more sensitive, robust outcome measures in young CF patients than traditional measures employed in the BEGIN study and that these novel measures will be more sensitive to treatment effects, tested here by comparison before and after triple-combination modulator therapy. By understanding the nature of early lung obstruction and characteristic changes in the liver and pancreas over time, we continue to lay the groundwork for more personalized medicine in the future.

Assessing treatment response and clinical benefit in children with CF who are clinically normal per standard outcomes (e.g., spirometry, pancreatic function) will become paramount as triplecombination therapy is extended to younger patients with milder CF clinical presentation than their historic peers. Here the sensitivity and profile free of ionizing-radiation exposure of MRI can be leveraged to follow an individual with CF over time to quantify changes with therapy-with additional spatial resolution unavailable from standard clinical testing.

Condition or DiseaseIntervention/Treatment
Cystic Fibrosis
Drug: 129XeDrug: 129Xe

Study Design

Study TypeInterventional
Actual Enrollment44 participants
Design AllocationNon-Randomized
Interventional ModelCrossover Assignment
MaskingSingle
Primary PurposeDiagnostic
Official TitleBEGIN Novel ImagiNG Biomarkers
Study Start DateApril 30, 2022
Actual Primary Completion Date2yrs 5mos from now
Actual Study Completion Date2yrs 5mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Pre Trikafta
129Xe MRI
Drug: 129Xe
Rapid spatial mapping of lung, liver, and pancreatic structure and function is now possible with a combination of hyperpolarized 129Xe and traditional proton MRI, all absent sedation and ionizing radiation.
Post Trikafta
129Xe MRI
Drug: 129Xe
Rapid spatial mapping of lung, liver, and pancreatic structure and function is now possible with a combination of hyperpolarized 129Xe and traditional proton MRI, all absent sedation and ionizing radiation.

Outcome Measures

Primary Outcome Measures
  1. Ventilation Defect Percentage change from baseline
    For pulmonary MRI, the primary outcome measure is the change in 129Xe ventilation defect percentage (VDP) from pre-therapy baseline to the one-year follow-up visit.
  2. Pancreas volume
    For pancreatic MRI, the primary outcome measure is change in pancreas volume normalized to BSA between pre-therapy baseline and one-year follow-up visit.
Secondary Outcome Measures
  1. Abdominal T1 values
    Changes in MRI T1 average in the liver and pancreas, from baseline to follow up at 1 year
  2. Lung reader score
    Changes in reader score for visible structural defects from proton MRI, from baseline to follow up at 1 year

Eligibility Criteria

Ages Eligible for Study(Child)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
1. Written informed consent (and assent where appropriate) obtained from the subject or subject's legal representative. 2. Willingness to adhere to the study-visit schedule and other protocol requirements. 3. Ages 6-8 years old at baseline MRI visit (may be enrolled up to 60 days before 6th birthday). 4. Documentation of CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria: 1. Sweat chloride equal to or greater than 60 mEq/liter by quantitative pilocarpine iontophoresis test 2. Two well-characterized mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene 5. Physician intent to prescribe triple-combination therapy 6. Clinically-stable with no respiratory tract infection at the time of enrollment. 7. No change in chronic maintenance therapies in the 28 days prior to enrollment. 8. Ability to cooperate with MRI procedures
Exclusion Criteria
1. Individuals currently on ivacaftor therapy (including Kalydeco, Orkambi, and Symdeko) and with at least one gating mutation. Gating mutations include G551D, G178R, S549N, S549R, G551S, G970R, G1244E, S1251N, S1255P, or G1349D. 2. Acute respiratory symptoms (e.g. wheezing) at the time of the MRI. 3. Acute respiratory infection, defined as increased cough, wheezing or respiratory rate in the 28 days prior to enrollment. 4. Chronic lung disease not related to CF 5. Chronic liver disease not related to CF 6. Acute pancreatitis, defined by clinical criteria (45). 7. Chronic pancreatic disease not related to CF. 8. Physical findings that would compromise the safety of the subject or the quality of the study data as determined at the discretion of the site investigator. 9. Any other condition that, in the opinion of the Site Investigator/designee, would preclude informed consent or assent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.

Contacts and Locations

Sponsors and CollaboratorsChildren's Hospital Medical Center, Cincinnati
Locations
University of Kansas Medical Center | Kansas City Kansas, United States, 66160Carrie Stevens | Cincinnati Ohio, United States, 45229University of Virginia | Charlottesville Virginia, United States, 22903
Investigators
Principal Investigator: Jason Woods, PhD, Children's Hospital Medical Center, Cincinnati