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

Cystic Fibrosis (CF) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05818319
• Other study ID #: CFPT29092022
• Status: Recruiting
• Phase: N/A
• Start date: June 1, 2023
• Est. completion date: December 2023

Study information

• Verified date: February 2023
• Source: University of Aarhus
• Contact: Amalie Q. Rousing, BM
• Email: arousing[@]biomed.au.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Cystic Fibrosis (CF)
• Fibrosis

Intervention

Other:
• 12 hours ETI pause
Patients with CF are randomly allocated to ETI pause lasting 12 hours.
• 36 hours ETI pause
Patients with CF are randomly allocated to ETI pause lasting either 36 hours.
• 60 hours ETI pause
Patients with CF are randomly allocated to ETI pause lasting either 60 hours.

Locations

Country	Name	City	State
Denmark	Department of Infectious Diseases, Aarhus University Hospital	Aarhus C	Midtjylland

Sponsors (1)

Lead Sponsor	Collaborator
University of Aarhus

Country where clinical trial is conducted

Denmark, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in cumulative urine bicarbonate excretion before, during, and after ETI pause.	Challenged urine HCO3- test: Quantification of urine bicarbonate excretion after an acute oral NaHCO3 challenge before, under, and after ETI pause.	At baseline, after 12/36/60 hours of therapy pause and after therapy is resumed.
Primary	Link between changes in ETI plasma concentration and changes in urine bicarbonate excretion.	Venous blood sampling: ETI plasma concentration measurement. Challenged urine HCO3- test: Quantification of urine bicarbonate excretion	At baseline, after 12/36/60 hours of therapy pause and after therapy is resumed.
Secondary	Link between plasma acid-base status and urine acid-base excretion.	Venous blood sampling: Venous acid-base measurements.	At baseline, after 12/36/60 hours of therapy pause and after therapy is resumed.
Secondary	Changes in plasma concentration of ETI during the trial.	Venous blood sampling: ETI plasma concentration measurement.	At baseline, after 12/36/60 hours of therapy pause and after therapy is resumed.
Secondary	Changes in acid-base and fluid status during the trial.	Venous blood sampling: Venous acid-base and fluid measurements.	At baseline, after 12/36/60 hours of therapy pause and after therapy is resumed.
Secondary	Changes in electrolytes during the trial.	Venous blood sampling: Venous electrolyte measurements. Challenged HCO3- urine test: Urine electrolyte measurements.	At baseline, after 12/36/60 hours of therapy pause and after therapy is resumed.