Canadian Observation Trial in CF Patients Undergoing Treatment With Ivacaftor

Completed

• Conditions: Cystic Fibrosis

• Registration Number: NCT03390985
• Lead Sponsor: Tanja Gonska

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-04-23
• Primary Completion: 2017-07-26
• Study Completion: 2017-07-26
• Status Verified: 2017-12
• Study First Submitted: 2017-12-18
• Study First Submitted QC: 2017-12-28
• Last Update Submitted: 2017-12-28
• Study First Posted: 2018-01-05
• Last Update Posted: 2018-01-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

• any patient being prescribed ivacaftor

Exclusion Criteria

• only relates to specific tests

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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
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

Secondary Outcome Measures

Name	Time	Method
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
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
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)
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
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 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 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 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
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