Losartan for Sickle Cell Disease

Overseen By Amanda Pfeiffer

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Hospital Medical Center, Cincinnati

Must be taking: Sickle cell therapies

Must not be taking: Renin-angiotensin inhibitors, Lithium, NSAIDs

Disqualifiers: Chronic transfusion, Congenital heart disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the medication losartan might benefit people with Sickle Cell Disease (SCD). Researchers aim to determine if losartan is safe and effective in stabilizing or reducing a specific body fluid measure (extracellular volume fraction) over 12 months. The trial seeks individuals who are 6 years or older, have a specific type of SCD (such as HbSS or Sbeta0-thalassemia), and are already on stable SCD therapy. Participants must be able to complete certain heart imaging tests without sedation. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

If you are on a stable dose of sickle cell disease-modifying therapy like Hydroxyurea, Voxelotor, L-Glutamine, or Crizanlizumab, you can continue taking them. However, you must stop any renin-angiotensin pathway inhibitors 2 weeks before joining the study and cannot be on chronic daily NSAIDs or lithium therapy.

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

Research has shown that losartan has been tested in people with sickle cell disease (SCD) to assess its safety and effects. Some studies have examined whether losartan could help with kidney problems related to SCD. The trials found no major changes in heart or lung health, indicating that people generally tolerated it well.

The FDA has already approved losartan for treating high blood pressure and certain heart issues, confirming its safety for those conditions. While its effects in SCD might differ, existing evidence of its safety in other conditions suggests it could also be safe for people with SCD. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Sickle Cell Disease?

Unlike the standard treatments for sickle cell disease, which primarily focus on managing pain and preventing complications through blood transfusions and hydroxyurea, losartan offers a unique approach by targeting the renin-angiotensin system. Researchers are intrigued by losartan because it has the potential to improve blood flow and reduce the risk of organ damage by decreasing inflammation and blood vessel constriction. This mechanism of action is different from current treatments and could offer a significant benefit in protecting organs without relying solely on traditional pain management strategies.

What evidence suggests that losartan might be an effective treatment for Sickle Cell Disease?

Research has shown that losartan, primarily used for high blood pressure, might also benefit people with Sickle Cell Disease (SCD). In studies involving patients with sickle cell nephropathy, losartan reduced albuminuria, a marker of kidney damage, while maintaining stable kidney function. Although losartan has not improved heart-related issues in SCD, it is known to protect kidneys in conditions like diabetes. Researchers believe losartan might reduce heart strain in people with SCD. These early findings suggest potential benefits, but further research is necessary to confirm its effectiveness for SCD. Participants in this trial will receive oral losartan to explore these potential benefits further. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for patients 6 years or older with Sickle Cell Disease (SCD), specifically HbSS or Sbeta0-thalassemia. They must be able to undergo heart imaging without sedation and have been on a stable dose of certain SCD therapies for 3 months. Excluded are those on chronic transfusion therapy, with severe kidney issues, pregnant women not using contraception, and others listed in the exclusion criteria.

Inclusion Criteria

I have been on a stable dose of medication for sickle cell disease for 3 months.

You are able to undergo an echocardiogram without needing to be asleep or numb.

I am 6 years old or older.

Exclusion Criteria

Inability to cooperate with CMR or echocardiography imaging

My sickle cell disease genotype is not listed in the study's accepted types.

You are allergic to angiotensin receptor II blockers.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral losartan daily for 12 months to assess its efficacy in stabilizing or decreasing extracellular volume fraction (ECV) in Sickle Cell Disease

12 months

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of myocardial fibrosis and exercise capacity

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Losartan

Trial Overview The study tests Losartan's safety and effectiveness in stabilizing or reducing heart muscle scarring over 12 months in SCD patients. It's an open-label pilot phase II trial enrolling 24 participants to gather preliminary data.

How Is the Trial Designed?

Group I: Losartan Experimental Treatment 1 Intervention

Participants will receive oral losartan as tablets or oral solution one time daily. The dosing will depend on age and will be based on drug label and dosing used in studies on patients with SCD.

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?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01989078?cond=Sickle%20cell%20nephropathy&viewType=Table&rank=8

NCT01989078 | Losartan for Sickle Cell Kidney Disease Losartan is an FDA-approved drug to treat blood pressure to protect the kidneys in people who have diseases like diabetes and blood pressure. It is not ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5546943/

Losartan for the Nephropathy of Sickle Cell Anemia There were no changes in cardiopulmonary outcomes after losartan therapy. However, there were baseline differences in cardiac phenotype based on the presence or ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1079979617303303

Losartan therapy decreases albuminuria with stable ... Losartan therapy for ≥ 1 year in sickle nephropathy results in lower albumin excretion with stable GFR. Filtration of neutral molecules ≥ 36 Å was not changed ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05012631

Losartan for Diffuse Myocardial Fibrosis in Sickle Cell ... The short-term goal is to obtain clinical pilot data regarding the safety and efficacy of losartan in stabilizing or decreasing extracellular volume fraction ( ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/ajh.24810

Losartan for the nephropathy of sickle cell anemia Our primary hypothesis was that losartan therapy would decrease the degree of albuminuria by ≥25% in participants with microalbuminuria (MicroA) ...

6. ashpublications.org ashpublications.org/hematology/article/2023/1/519/506453/Using-disease-modifying-therapies-in-sickle-cell

Using disease-modifying therapies in sickle cell disease This article reviews important historic and recent drug trials for SCD, highlighting regulatory agency–approved drug therapies and our approach to the use of ...

7. withpower.com withpower.com/trial/phase-3-fibrosis-8-2021-c59e3

Losartan for Sickle Cell Disease Losartan. Trial Overview The study tests Losartan's safety and effectiveness in stabilizing or reducing heart muscle scarring over 12 months in SCD patients.