CFTR Gene Mutation, Cystic Fibrosis (CF)
Conditions
Brief summary
In cystic fibrosis (CF) renal base excretion is impaired, due to mutations in the Cystic Fibrosis Transmembrane Regulator (CFTR) gene, since CFTR function is crucial in regulation of the kidney's HCO3- excretion. The investigators suggest that challenged urine HCO3- excretion is a biomarker of CFTR function, which can be used to evaluate the extent of CFTR dysfunction and the possible correcting effects of CFTR modulating therapy. This study aims to evaluate changes in challenged urine HCO3- excretion in CF patients, who are currently in treatment with the triple CFTR modulator combination therapy, Elexacaftor/tezacaftor/ivacaftor (ETI), before, during, and after a short treatment pause.
Interventions
OTHER12 hours ETI pause
Patients with CF are randomly allocated to ETI pause lasting 12 hours.
OTHER36 hours ETI pause
Patients with CF are randomly allocated to ETI pause lasting either 36 hours.
OTHER60 hours ETI pause
Patients with CF are randomly allocated to ETI pause lasting either 60 hours.
Sponsors
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
CF patients will perform a challenged urine bicarbonate test three times during this trial; 1) before, 2) during, and 3) after ETI therapy pause. Each test performance takes 90 min. and is accompanied by baseline blood sampling. First, a baseline urine sample is collected. Then the test person ingests 79 mg. NaHCO3/kg body weight dissolved in tap water (2,25 mL/kg body weight) together with the same amount of clean tap water. After 90 min. the test person delivers the second urine sample, and the test is completed. The test should preferably be performed between breakfast and lunch, at least one hour after intake of food. There should be at least three days between each test. CF patients will be randomly allocated to an ETI treatment pause for either 12, 36, or 60 hours. Treatment will be resumed immediately after the pause is finished.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult (age \>17 years) CF patients. * Normal kidney function estimated by eGFR\>90. * Adults capable of understanding and voluntarily consenting.
Exclusion criteria
* Critical acute illness. * Severe lung disease (ppFEV1\<40%). * Adults not capable of understanding and voluntarily consenting.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in cumulative urine bicarbonate excretion before, during, and after ETI pause. | At baseline, after 12/36/60 hours of therapy pause and after therapy is resumed. | Challenged urine HCO3- test: Quantification of urine bicarbonate excretion after an acute oral NaHCO3 challenge before, under, and after ETI pause. |
| Link between changes in ETI plasma concentration and changes in urine bicarbonate excretion. | At baseline, after 12/36/60 hours of therapy pause and after therapy is resumed. | Venous blood sampling: ETI plasma concentration measurement. Challenged urine HCO3- test: Quantification of urine bicarbonate excretion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Link between plasma acid-base status and urine acid-base excretion. | At baseline, after 12/36/60 hours of therapy pause and after therapy is resumed. | Venous blood sampling: Venous acid-base measurements. |
| Changes in plasma concentration of ETI during the trial. | At baseline, after 12/36/60 hours of therapy pause and after therapy is resumed. | Venous blood sampling: ETI plasma concentration measurement. |
| Changes in acid-base and fluid status during the trial. | At baseline, after 12/36/60 hours of therapy pause and after therapy is resumed. | Venous blood sampling: Venous acid-base and fluid measurements. |
| Changes in electrolytes during the trial. | At baseline, after 12/36/60 hours of therapy pause and after therapy is resumed. | Venous blood sampling: Venous electrolyte measurements. Challenged HCO3- urine test: Urine electrolyte measurements. |
Countries
Denmark
Contacts
Primary ContactAmalie Q. Rousing, BM
Outcome results
None listed