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

Phase 2
Recruiting
Conditions
Cystic Fibrosis
Interventions
Drug: Placebo
Registration Number
NCT06364176
Lead Sponsor
University of Kansas Medical Center
Brief Summary

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.

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
42
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo twice daily through week 12
LosartanLosartanLosartan 25mg twice daily for one week followed by 50mg twice daily through week 12.
Primary Outcome Measures
NameTimeMethod
Sweat chlorideBaseline through week 12

Change in sweat chloride concentration

Secondary Outcome Measures
NameTimeMethod
Inflammatory mediators - systemicBaseline through week 12

Change in plasma levels of inflammatory mediators (interleukin-1beta, interleukin-8, tumor necrosis factor-alpha)

Lung function - relativeBaseline through week 12

Relative change in ppFEV1

TGF-beta1 - systemicBaseline through week 12

Change in plasma levels of TGF-beta1

CFQ-RBaseline through week 12

Change in CF questionnaire revised (CFQ-R); scale 0-100 with higher scores indicating better quality of life

Adverse eventsBaseline through week 12

Cumulative incidence of adverse events

Lung function - absoluteBaseline through week 12

Absolute change in percent predicted forced expiratory volume in one second (ppFEV1)

Transforming growth factor (TGF)-beta1 - airwayBaseline through week 12

Change in nasal fluid levels of TGF-beta1

Inflammatory mediators - airwayBaseline through week 12

Change in concentration nasal fluid levels of inflammatory mediators (interleukin-1beta, interleukin-8, tumor necrosis factor-alpha)

Trial Locations

Locations (1)

University of Kansas Medical Center

🇺🇸

Kansas City, Kansas, United States

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