Cystic Fibrosis
Conditions
Brief summary
Specific aims: 1. 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 2. To examine the relation between the individual response to ivacaftor and the presence of modifier genes associated with CF disease severity, 3. To assess altered CFTR function using new available in vivo tests, 4. To validate newly developed in vivo sweat tests with well established functional tests, 5. 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, 6. To examine response in other CF-specific features such as aqua wrinkling. 7. To examine if sleep/activity level changes. 8. To establish a biorepository to enable further investigations.
Interventions
None listed
Sponsors
Tanja Gonska
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* any patient being prescribed ivacaftor
Exclusion criteria
* only relates to specific tests
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Functional in vivo Cystic fibrosis transmembrane conductor regulator (CFTR) tests: Nasal Potential difference (NPD) measurements | 7 study visits over a 2 year period | NPD is measured to assess CFTR function as difference in mV between post and pre-drug start |
| Functional in vivo test: Beta-adrenergic sweat secretion test | 7 study visits over a 2 year period | The beta-adrenergic sweat secretion test is measured as ratio of beta-adrenergic/cholinergic sweat secretion as difference between post and pre-drug start |
| Functional in vitro test: Rectal tissue biopsies to measure CFTR function in vitro using Ussing chamber studies and organoids | one study visit | Rectal tissue specimen is being used to measure the response to ivcaftor of individual CF patients in vitro |
| Functional in vitro test: Collect nasal brushes for CFTR to generate nasal cell cultures for the assessment of ivacaftor response and CFTR function | 2 study visits in 6 months | Nasal cultures are used to measure the response to ivcaftor in vitro as difference of the forskolin-induced response of CFTR to ivacaftor |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measurements of the pancreas function using serum trypsinogen | 4 study visits in 2 years | Serum trypsinogen is determined in nmol/L pre and post-drug |
| Assessment of the nutritional status | 4 study visits in 2 years | 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 |
| Measurement of aqua wrinkling | 2 study visits in 3 months | 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 |
| Assessment of pulmonary radiological changes using high resolution CT | 4 study visits in 2 years | Radiological pulmonary changes are being assessed using high resolution CT pre and post-drug (descriptive and Bhalla score) |
| Assessment of glucose tolerance | 4 study visits in 2 years | 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 |
| Measurements of the resting energy expenditure | 4 study visits in 2 years | The resting energy expenditure is measured using indirect calorimetry in kcal/d pre and post-post |
| Measurement of exhaled fractionated nitrogen oxide (FeNo) | 5 study visits in 1 year | the fraction of the exhaled NO in % In the expiration of CF patients is being measured pre-and post-drug |
| Measurements of the lung clearance index | 5 study visits in 1 year | Multiple breath wash-out technique is being used to measure the lung clearance index (no unit) pre and post-drug |
| Measurements of the pancreas function using fecal elastase test | 4 study visits in 2 years | Fecal elastase in stool is determined in microg/g stool pre and post-drug |
Outcome results
None listed