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

NCT05818319 | Recruiting

• 1 other identifier: CFPT29092022
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Cystic Fibrosis (CF); CFTR Gene Mutation

Outcome Measures

Primary Outcomes (2)

• 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.

• 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 Outcomes (4)

• 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.

• Changes in plasma concentration of ETI during the trial.

  At baseline, after 12/36/60 hours of therapy pause and after therapy is resumed.

• 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.

• Changes in electrolytes during the trial.

  At baseline, after 12/36/60 hours of therapy pause and after therapy is resumed.

Study Arms (3)

12 hours ETI pause

OTHER

Other: 12 hours ETI pause

36 hours ETI pause

OTHER

Other: 36 hours ETI pause

60 hours ETI pause

OTHER

Other: 60 hours ETI pause

Interventions

12 hours ETI pause OTHER

Patients with CF are randomly allocated to ETI pause lasting 12 hours.

12 hours ETI pause

36 hours ETI pause OTHER

Patients with CF are randomly allocated to ETI pause lasting either 36 hours.

36 hours ETI pause

60 hours ETI pause OTHER

Patients with CF are randomly allocated to ETI pause lasting either 60 hours.

60 hours ETI pause

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult (age \>17 years) CF patients.
• Normal kidney function estimated by eGFR\>90.
• Adults capable of understanding and voluntarily consenting.

You may not qualify if:

• Critical acute illness.
• Severe lung disease (ppFEV1\<40%).
• Adults not capable of understanding and voluntarily consenting.

Sponsors & Collaborators

• University of Aarhus: lead

Study Sites (1)

Department of Infectious Diseases, Aarhus University Hospital

Aarhus C, Central Jutland, 8000, Denmark

RECRUITING

Related Publications (2)

• 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.

  PMID: 32703846 BACKGROUND

• 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.

  PMID: 36315944 BACKGROUND

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Officials

• Jens G. Leipziger

  Department of Biomedicine, Aarhus University, Denmark

  PRINCIPAL INVESTIGATOR

• Majbritt Jeppesen

  Department of Infectious Diseases, Aarhus University Hospital, Denmark

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amalie Q. Rousing, BM

CONTACT

arousing@biomed.au.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 28, 2023
• First Posted: April 18, 2023
• Study Start: June 1, 2023
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: February 19, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)