BEGIN Novel ImagiNG Biomarkers

Overview

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).

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.

Eligibility

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.