Canadian Observation Trial in CF Patients Undergoing Treatment With Ivacaftor

Study Overview
=================
Brief Summary
-----------------
Specific aims: To elucidate the biological mechanism that leads to pulmonary and nutritional improvement in CF patients following treatment with ivacaftor using advanced techniques to assess changes of the pulmonary and nutritional status To examine the relation between the individual response to ivacaftor and the presence of modifier genes associated with CF disease severity, To assess altered CFTR function using new available in vivo tests, To validate newly developed in vivo sweat tests with well established functional tests, To establish correlation between the CFTR response to Vx-770 measured in a new ex vivo method (organoids) and the actual clinical and/or functional response in individual patients, To examine response in other CF-specific features such as aqua wrinkling. To examine if sleep/activity level changes. To establish a biorepository to enable further investigations.

Official Title
-----------------
Canadian Observation Trial in CF Patients Undergoing Treatment With Ivacaftor

Conditions
-----------------
Cystic Fibrosis

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: any patient being prescribed ivacaftor Exclusion Criteria: only relates to specific tests

Ages Eligible for Study
-----------------
Minimum Age: 6 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional in vivo Cystic fibrosis transmembrane conductor regulator (CFTR) tests: Nasal Potential difference (NPD) measurements | NPD is measured to assess CFTR function as difference in mV between post and pre-drug start | 7 study visits over a 2 year period | 
| Functional in vivo test: Beta-adrenergic sweat secretion test | The beta-adrenergic sweat secretion test is measured as ratio of beta-adrenergic/cholinergic sweat secretion as difference between post and pre-drug start | 7 study visits over a 2 year period | 
| Functional in vitro test: Rectal tissue biopsies to measure CFTR function in vitro using Ussing chamber studies and organoids | Rectal tissue specimen is being used to measure the response to ivcaftor of individual CF patients in vitro | one study visit | 
| Functional in vitro test: Collect nasal brushes for CFTR to generate nasal cell cultures for the assessment of ivacaftor response and CFTR function | Nasal cultures are used to measure the response to ivcaftor in vitro as difference of the forskolin-induced response of CFTR to ivacaftor | 2 study visits in 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of aqua wrinkling | CF patients response to submerge in water for 5 min to develop a skin phenomenon known as aqua wrinkling is being measured subjectively pre and post-drug | 2 study visits in 3 months | 
| Measurement of exhaled fractionated nitrogen oxide (FeNo) | the fraction of the exhaled NO in % In the expiration of CF patients is being measured pre-and post-drug | 5 study visits in 1 year | 
| Measurements of the lung clearance index | Multiple breath wash-out technique is being used to measure the lung clearance index (no unit) pre and post-drug | 5 study visits in 1 year | 
| Measurements of the pancreas function using fecal elastase test | Fecal elastase in stool is determined in microg/g stool pre and post-drug | 4 study visits in 2 years | 
| Measurements of the pancreas function using serum trypsinogen | Serum trypsinogen is determined in nmol/L pre and post-drug | 4 study visits in 2 years | 
| Assessment of the nutritional status | Nutritional status is assessed using the BODPOD in kg fat or non-fat mass change or percentage fat or non-fat mass change pre and post-drug | 4 study visits in 2 years | 
| Measurements of the resting energy expenditure | The resting energy expenditure is measured using indirect calorimetry in kcal/d pre and post-post | 4 study visits in 2 years | 
| Assessment of pulmonary radiological changes using high resolution CT | Radiological pulmonary changes are being assessed using high resolution CT pre and post-drug (descriptive and Bhalla score) | 4 study visits in 2 years | 
| Assessment of glucose tolerance | Glucose tolerance is being assessed using the organ glucose tolerance test and glucose levels 2 hrs post in mmol/L will be compared pre and post-drug | 4 study visits in 2 years |