Canadian Observation Trial in CF Patients Undergoing Treatment With Ivacaftor (G551D)

• ClinicalTrials.gov Identifier: NCT03390985
• Recruitment Status: Completed
• First Posted: January 5, 2018
• Last Update Posted: January 5, 2018
• Sponsor: Tanja Gonska
• Information provided by (Responsible Party): Tanja Gonska, The Hospital for Sick Children

Study Description

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.

Condition or disease
Cystic Fibrosis

Study Design

• Study Type: Observational
• Actual Enrollment: 18 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Canadian Observation Trial in CF Patients Undergoing Treatment With Ivacaftor
• Actual Study Start Date: April 23, 2013
• Actual Primary Completion Date: July 26, 2017
• Actual Study Completion Date: July 26, 2017

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Functional in vivo Cystic fibrosis transmembrane conductor regulator (CFTR) tests: Nasal Potential difference (NPD) measurements [ Time Frame: 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
2. Functional in vivo test: Beta-adrenergic sweat secretion test [ Time Frame: 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
3. Functional in vitro test: Rectal tissue biopsies to measure CFTR function in vitro using Ussing chamber studies and organoids [ Time Frame: one study visit ]
   Rectal tissue specimen is being used to measure the response to ivcaftor of individual CF patients in vitro
4. Functional in vitro test: Collect nasal brushes for CFTR to generate nasal cell cultures for the assessment of ivacaftor response and CFTR function [ Time Frame: 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 Outcome Measures :

1. Measurement of aqua wrinkling [ Time Frame: 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
2. Measurement of exhaled fractionated nitrogen oxide (FeNo) [ Time Frame: 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
3. Measurements of the lung clearance index [ Time Frame: 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
4. Measurements of the pancreas function using fecal elastase test [ Time Frame: 4 study visits in 2 years ]
   Fecal elastase in stool is determined in microg/g stool pre and post-drug
5. Measurements of the pancreas function using serum trypsinogen [ Time Frame: 4 study visits in 2 years ]
   Serum trypsinogen is determined in nmol/L pre and post-drug
6. Assessment of the nutritional status [ Time Frame: 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
7. Measurements of the resting energy expenditure [ Time Frame: 4 study visits in 2 years ]
   The resting energy expenditure is measured using indirect calorimetry in kcal/d pre and post-post
8. Assessment of pulmonary radiological changes using high resolution CT [ Time Frame: 4 study visits in 2 years ]
   Radiological pulmonary changes are being assessed using high resolution CT pre and post-drug (descriptive and Bhalla score)
9. Assessment of glucose tolerance [ Time Frame: 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

Biospecimen Retention:   Samples Without DNA

sputum, stool, plasma

Eligibility Criteria

• Ages Eligible for Study: 6 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

CF patients with any of the following mutations G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, G1349D and G970R approved by Health Canada to receive ivacaftor.

Criteria

Inclusion Criteria:

• any patient being prescribed ivacaftor

Exclusion Criteria:

• only relates to specific tests

Contacts and Locations

No Contacts or Locations Provided

More Information

• Responsible Party: Tanja Gonska, Principal Investigator, The Hospital for Sick Children
• ClinicalTrials.gov Identifier: NCT03390985
• Other Study ID Numbers: 1000036224
• First Posted: January 5, 2018
• Last Update Posted: January 5, 2018
• Last Verified: December 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Cystic Fibrosis; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases