Targeting Inflammation With Losartan to Improve Response to Modulator Therapy in Cystic Fibrosis.

Targeting Inflammation With Losartan to Improve Response to Modulator Therapy in Cystic Fibrosis

The goal of this clinical trial is to test use of losartan in those with cystic fibrosis (CF) on modulator therapy. The main question it aims to answer is if treatment with losartan improves response of the CF transmembrane conductance regulator (CFTR) channel to modulator therapy.

Participants will be asked take losartan or placebo for twelve weeks and will have changes in sweat chloride levels measured as a marker of CFTR function.

Study Overview

• Status: Recruiting
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Losartan; Drug: Placebo

Detailed Description

This is a randomized, placebo-controlled, parallel group clinical trial in those those with CF on elexacaftor/tezacaftor/ivacaftor to determine if treatment with losartan improves response to modulator therapy using sweat chloride as an marker of CFTR function.

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Carolina Aguiar; Phone Number: 9139459295; Email: caguiar@kumc.edu
• Study Contact Backup: Name: Heidi Hellwig; Phone Number: 9135886045; Email: hhellwig@kumc.edu

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Recruiting
      • University of Kansas Medical Center
      • Contact: Carolina Aguiar; Phone Number: 9139459295
      • Sub-Investigator: Andreas Schmid, M.D.
      • Contact: Charles Bengtson, MD, MSc; Phone Number: 913-588-6000
      • Sub-Investigator: Matthias Salathe, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Established diagnosis of cystic fibrosis
• Age 12 years and older
• Stable use of elexacaftor/tezacaftor/ivacaftor for 90 days prior to enrollment
• Sweat chloride concentration 50 mmol/L or greater while on elexacaftor/tezacaftor/ivacaftor

Exclusion Criteria:

• Prior lung transplant
• BMI <18
• CF pulmonary exacerbation requiring hospitalization or intravenous antibiotics in the preceding 30 days
• Systemic corticosteroid or regular non-steroidal anti-inflammatory use in the preceding 30 days
• Chronic use of angiotensin receptor blockers or angiotensin converting enzyme inhibitors
• Concomitant use of medications known to interact with losartan, including aliskiren
• Chronic renal insufficiency (creatinine clearance <45 ml/min)
• Pregnancy or lactation
• Inability or unwillingness to comply with approved contraceptive method during the study period (females of childbearing age)
• In the opinion of the investigator any severe or acute or chronic condition or laboratory abnormality that may increase the risk associated with trial participation or make the participant inappropriate for enrollment
• Participation in another interventional trial that, in the opinion of the investigator, has the potential to affect the primary outcome

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Losartan; Losartan 25mg twice daily for one week followed by 50mg twice daily through week 12.	Drug: Losartan; Treatment with losartan through week 12
Placebo Comparator: Placebo; Placebo twice daily through week 12	Drug: Placebo; Treatment with placebo through week 12

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sweat chloride	Change in sweat chloride concentration	Baseline through week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lung function - absolute	Absolute change in percent predicted forced expiratory volume in one second (ppFEV1)	Baseline through week 12
Lung function - relative	Relative change in ppFEV1	Baseline through week 12
Transforming growth factor (TGF)-beta1 - airway	Change in nasal fluid levels of TGF-beta1	Baseline through week 12
TGF-beta1 - systemic	Change in plasma levels of TGF-beta1	Baseline through week 12
Inflammatory mediators - airway	Change in concentration nasal fluid levels of inflammatory mediators (interleukin-1beta, interleukin-8, tumor necrosis factor-alpha)	Baseline through week 12
Inflammatory mediators - systemic	Change in plasma levels of inflammatory mediators (interleukin-1beta, interleukin-8, tumor necrosis factor-alpha)	Baseline through week 12
CFQ-R	Change in CF questionnaire revised (CFQ-R); scale 0-100 with higher scores indicating better quality of life	Baseline through week 12
Adverse events	Cumulative incidence of adverse events	Baseline through week 12

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center
• Investigators: Principal Investigator: Charles Bengtson, MD, MSc, University of Kansas Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: March 6, 2024
• First Submitted That Met QC Criteria: April 10, 2024
• First Posted (Actual): April 15, 2024

Study Record Updates

• Last Update Posted (Actual): May 2, 2025
• Last Update Submitted That Met QC Criteria: April 29, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: losartan
• Additional Relevant MeSH Terms: Pathologic Processes; Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Inflammation; Fibrosis; Cystic Fibrosis; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Losartan
• Other Study ID Numbers: STUDY00149479

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No