Orkambi Treatment in 2 to 5 Year Old Children With CF
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Study type: Observational

Summary: 
      The purpose of this observational research study is to determine the effects of clinically
      prescribed Orkambi treatment on 2 to 5 year old children homozygous for the F508del Mutations
      in the Cystic fibrosis transmembrane conductance regulator (CFTR) gene on sleeping energy
      expenditure, growth status and gut health and function.
    

Detailed description: 
      Orkambi is a novel FDA approved (August, 2018) therapy for use in patients with cystic
      fibrosis (CF) who are 2 to 5 years of age and homozygous for F508del mutations in the CFTR
      gene. It is a combination of lumacaftor and ivacaftor that addresses both the processing and
      gating defects of the F508del mutation. This investigator-initiated study is designed to
      evaluate the nutritional, growth and GI impact of Orkambi treatment for this unique younger
      (2 to 5 years) patient cohort. This proposal extends previous highly informative nutrition
      and weight gain investigation of ivacaftor treatment in people with CF gating mutations to
      another CFTR modulator treatment (Orkambi) in people homozygous for F508del mutations. The
      primary aims of the study are to evaluate the impact of 24 weeks of Orkambi treatment in 2 to
      5 year old subjects with CF homozygous for F508del mutations on sleeping or resting energy
      expenditure, growth status and gut health and function in n=32 children ages 2.0 to 5.9 years
      of age. Protocol evaluations will occur at baseline (pre-treatment) and 12 and 24 weeks after
      clinically prescribed Orkambi treatment has begun. Other outcomes of significant clinical
      interest in young subjects with CF will be explored. All subjects will be evaluated as
      outpatient at The Children's Hospital of Philadelphia, and will be recruited both regionally
      and nationally to ensure timely enrollment.
    

Intervention name(s): Orkambi
Intervention type(s): Drug
Intervention description(s): Orkambi is a novel approved therapy for use in people homozygous for the F508del mutation in the CFTR gene. It is a combination of lumacaftor (VX-809) and ivacaftor( VX-770) that addresses both the processing and gating defects of the F508del mutation. The small-molecule corrector lumacaftor corrects the F508del processing defect and increases epithelial delivery of CFTR protein1. Ivacaftor is a CFTR potentiator that increases the channel open probability in F508del-mutant CFTRs that undergo epithelial delivery in vitro and has an additive effect with lumacaftor on chloride transport (2,3,4,5).
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        2 to 5 year old subjects with a diagnosis of cystic fibrosis and homozygous for F508del
        mutations and who are in a usual state of good health with a clinical decision to start
        orkambi treatment.
      
Biospecimen description: 
      Blood, stool sample
    
Keywords: CF; CFTR; Cystic Fibrosis