Cystic Fibrosis in the Kidney: Monitoring the Effectiveness of Elexacaftor/tezacaftor/ivacaftor in Urine After a Short Pause of Therapy

Not Applicable

Recruiting

• Conditions: CFTR Gene Mutation; Cystic Fibrosis (CF)
• Interventions: Other: 12 hours ETI pause; Other: 36 hours ETI pause; Other: 60 hours ETI pause

• Registration Number: NCT05818319
• Lead Sponsor: University of Aarhus

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-03-28
• Study First Submitted QC: 2023-04-17
• Study First Posted: 2023-04-18
• Study Start: 2023-06-01
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-17
• Last Update Posted: 2025-02-19
• Primary Completion: 2025-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
12 hours ETI pause	12 hours ETI pause	-
36 hours ETI pause	36 hours ETI pause	-
60 hours ETI pause	60 hours ETI pause	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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 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.

Trial Locations

Locations (1)

Department of Infectious Diseases, Aarhus University Hospital; 🇩🇰 Aarhus C, Midtjylland, Denmark