Losartan for Cystic Fibrosis

Overseen By Matthias Salathe, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Kansas Medical Center

Must not be taking: ACE inhibitors, NSAIDs, Anticoagulants, Corticosteroids

Disqualifiers: Unstable lung disease, Smoking history, Hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 14 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests losartan, a medication typically used for high blood pressure, to determine if it aids mucociliary clearance (the process of clearing mucus from the lungs) in individuals with cystic fibrosis who cannot use CFTR therapies. The trial targets patients with mild to moderate lung disease who produce sputum daily. Those with cystic fibrosis and any known mutation, not on CFTR therapies, might find this trial suitable. Participants will take losartan daily, and researchers will monitor its effects on lung function over 12 weeks. As an Early Phase 1 trial, this research aims to understand how losartan works in people with cystic fibrosis.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you cannot participate if you are using certain medications like ACE inhibitors, NSAIDs, or oral corticosteroids within 6 weeks. If you are on chronic antibiotics, you must have completed at least 2 full cycles before joining.

Is there any evidence suggesting that losartan is likely to be safe for humans?

Research has shown that losartan, a drug typically used for high blood pressure, is under study for potential benefits in treating cystic fibrosis. Early studies suggest that losartan is generally safe and might help reduce inflammation in individuals with this condition. Specifically, patients in these studies demonstrated improved lung function without major side effects. The FDA has already approved losartan for other uses, so its safety at normal doses is well understood. In previous research, most participants tolerated it well, and serious side effects were uncommon. These findings provide some confidence about its safety for those considering joining a trial with losartan for cystic fibrosis. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cystic fibrosis?

Unlike the standard treatments for cystic fibrosis, such as antibiotics and medications to thin mucus, Losartan is unique because it is traditionally used to manage high blood pressure and heart failure. Researchers are excited about Losartan because it targets inflammation and fibrosis, which are significant issues in cystic fibrosis. This drug could potentially reduce lung damage by addressing these underlying problems, offering a new way to improve lung function and quality of life for patients.

What evidence suggests that losartan might be an effective treatment for cystic fibrosis?

Studies have shown that losartan, the treatment being tested in this trial, can improve the body's ability to clear mucus, often affected by inflammation and cystic fibrosis. This benefit appears to occur independently of losartan's usual role in controlling blood pressure. Research suggests that reducing inflammation with losartan could enhance mucus clearance in people with cystic fibrosis. This is promising because better mucus clearance may reduce lung infections and improve breathing in these patients. ^{2 3 4 6 7}

Who Is on the Research Team?

Matthias Salathe, MD

Principal Investigator

University of Kansas

Are You a Good Fit for This Trial?

Adults over 18 with cystic fibrosis not treated with CFTR therapy can join. They should have mild to moderate lung disease, be able to produce sputum daily, and have an FEV1 ≥40% of predicted. Participants need a negative COVID-19 test before testing, must not smoke or have quit for at least a year, and females must use strict birth control.

Inclusion Criteria

My lung condition is considered mild to moderate.

You need to have a negative COVID-19 test within 3 days before the test for the clinical trial.

You need to have a certain level of lung function, called FEV1, to be eligible for the study.

Exclusion Criteria

You are not able to do the breathing tests required for the study.

I regularly use NSAIDs, potassium supplements, aliskiren, or am on anticoagulation therapy.

I am a current or former smoker who quit less than a year ago or have smoked more than 10 pack-years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive a daily dose of 50 mg losartan for 7 days, followed by 100 mg daily for 12 weeks

14 weeks

1 safety visit after 7 days, regular monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Losartan

Trial Overview The trial is studying the effect of Losartan on mucociliary clearance in cystic fibrosis patients ineligible for CFTR therapies. It's a small-scale proof of concept study designed to understand how this medication might help clear mucus from the lungs.

How Is the Trial Designed?

Group I: losartan Experimental Treatment 1 Intervention

a daily dose of 50 mg losartan for 7 days (for tolerability). Then, the losartan dose will be increased to 100 mg daily for 12 weeks.

Losartan is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Cozaar for:

• Hypertension
• Diabetic nephropathy
• Stroke prevention in hypertension and left ventricular hypertrophy

Approved in European Union as Cozaar for:

• Hypertension
• Diabetic nephropathy
• Heart failure

Approved in Canada as Cozaar for:

• Hypertension
• Diabetic nephropathy
• Heart failure

Who Is Running the Clinical Trial?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6999107/

Losartan Rescues Inflammation-related Mucociliary ... Conclusions: Losartan effectively reversed CF- and inflammation-associated mucociliary dysfunction, independent of its angiotensin receptor blockade. Keywords: ...

2. clinicaltrial.be clinicaltrial.be/en/details/69420?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

Effect of Losartan in Cystic Fibrosis (CF)-NIH Grant #133... These findings suggest that effective and safe anti-inflammatory therapy has the potential to improve mucociliary dysfunction in CF patients, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03206788

NCT03206788 | Losartan and Inflammation in Cystic Fibrosis The purpose of the study is to examine if a specific drug called losartan (Cozaar ®), generally used to treat high blood pressure and to protect kidneys ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9151698/

Losartan ameliorates TGF-β1–induced CFTR dysfunction ... The efficacy of modulator therapy in a CF inflammatory airway environment has been controversial, with some studies showing improved functional CFTR recovery (5 ...

5. atsjournals.org atsjournals.org/doi/abs/10.1164/rccm.201905-0990OC

Losartan Rescues Inflammation-related Mucociliary ... Losartan effectively reversed CF- and inflammation-associated mucociliary dysfunction, independent of its angiotensin receptor blockade.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03435939?cond=%22Cystic%20Fibrosis%22&intr=%22Losartan%22&viewType=Table&rank=1

Effect of Losartan in Cystic Fibrosis (CF)-NIH Grant #133240 Members are chosen based on the scientific skills and knowledge needed to monitor the particular trial. Also called a data safety and monitoring board, or DSMB.

7. centerwatch.com centerwatch.com/clinical-trials/listings/NCT03435939/effect-of-losartan-in-cystic-fibrosis-cf-nih-grant-133240

Effect of Losartan in Cystic Fibrosis (CF)-NIH Grant #133240 The goal of this study is to execute a small clinical proof of concept trial: To examine the effects of losartan on mucociliary clearance (MCC) in patients ...