Clinical trial NCT05818319: Cystic Fibrosis in the Kidney: Monitoring the Effectiveness of Elexacaftor/tezacaftor/ivacaftor in Urine After a Short Pause of Therapy
Official title: Cystic Fibrosis in the Kidney: Monitoring the Effectiveness of Elexacaftor/tezacaftor/ivacaftor in Urine After a Short Pause of Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cystic Fibrosis (CF)
CFTR Gene Mutation
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2023-04-18
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: DIAGNOSTIC

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Difference in cumulative urine bicarbonate excretion before, during, and after ETI pause.
timeFrame: At baseline, after 12/36/60 hours of therapy pause and after therapy is resumed.
measure: Link between changes in ETI plasma concentration and changes in urine bicarbonate excretion.
timeFrame: At baseline, after 12/36/60 hours of therapy pause and after therapy is resumed.
Secondary outcomes:
measure: Link between plasma acid-base status and urine acid-base excretion.
timeFrame: At baseline, after 12/36/60 hours of therapy pause and after therapy is resumed.
measure: Changes in plasma concentration of ETI during the trial.
timeFrame: At baseline, after 12/36/60 hours of therapy pause and after therapy is resumed.
measure: Changes in acid-base and fluid status during the trial.
timeFrame: At baseline, after 12/36/60 hours of therapy pause and after therapy is resumed.
measure: Changes in electrolytes during the trial.
timeFrame: At baseline, after 12/36/60 hours of therapy pause and after therapy is resumed.
Other outcomes:
Locations:
city: Aarhus C
country: Denmark
facility: Department of Infectious Diseases, Aarhus University Hospital
state: Midtjylland
Study officials:
affiliation: Department of Biomedicine, Aarhus University, Denmark
name: Jens G. Leipziger
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Infectious Diseases, Aarhus University Hospital, Denmark
name: Majbritt Jeppesen
role: PRINCIPAL_INVESTIGATOR
References:
citation: Berg P, Svendsen SL, Sorensen MV, Larsen CK, Andersen JF, Jensen-Fangel S, Jeppesen M, Schreiber R, Cabrita I, Kunzelmann K, Leipziger J. Impaired Renal HCO3- Excretion in Cystic Fibrosis. J Am Soc Nephrol. 2020 Aug;31(8):1711-1727. doi: 10.1681/ASN.2020010053. Epub 2020 Jul 23.
citation: Berg P, Sorensen MV, Rousing AQ, Vebert Olesen H, Jensen-Fangel S, Jeppesen M, Leipziger J. Challenged Urine Bicarbonate Excretion as a Measure of Cystic Fibrosis Transmembrane Conductance Regulator Function in Cystic Fibrosis. Ann Intern Med. 2022 Nov;175(11):1543-1551. doi: 10.7326/M22-1741. Epub 2022 Nov 1.