Losartan for Diffuse Myocardial Fibrosis in Sickle Cell Disease

NCT05012631 | Recruiting Phase 2 FDA Drug

• 1 other identifier: Losartan-CMR
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a pilot, phase II, open-label study of the angiotensin II receptor blocker, losartan, in patients with Sickle Cell Disease (SCD) 6 years or older for 12 months. The investigators will enroll 24 patients with SCD over the course of 1 year with a goal to complete all study procedures in 2 years. The short-term goal is to obtain clinical pilot data regarding the safety and efficacy of losartan in stabilizing or decreasing extracellular volume fraction (ECV) after 12 months of therapy.

Conditions

Sickle Cell Disease; Diffuse Myocardial Fibrosis

Outcome Measures

Primary Outcomes (1)

• Change in extracellular volume fraction (ECV) after 1 year of losartan treatment

  Efficacy of losartan in stabilizing or reducing ECV (diffuse myocardial fibrosis) in SCD after one year.

  after 1 year of losartan treatment.

Secondary Outcomes (3)

• Change in Diastolic Function

  after 1 year of losartan treatment.

• Change in Exercise Capacity

  after 1 year of losartan treatment.

• Predicting Myocardial Fibrosis

  At baseline and after one year of losartan treaement

Study Arms (1)

Losartan

EXPERIMENTAL

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.

Drug: Losartan

Interventions

Losartan DRUG

Losartan dosing for participants \<16 years will be 0.7 mg/kg (maximum of 50 mg) once daily. The dose can be increased to 1.4 mg/kg (maximum of 100 mg once daily) after 2 weeks if the dose was tolerated (no hypotension or hyperkalemia). For patients ≥16 years, the starting dose will be 50 mg once daily which can be increased to 100 mg daily if tolerated after 2 weeks.

Losartan

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• years old or older
• Diagnosis of HbSS or Sbeta0-thalassemia
• Ability to cooperate with and undergo CMR without sedation or anesthesia
• Ability to cooperate with and undergo echocardiogram without sedation or anesthesia
• Patients who are on a stable dose of sickle cell disease-modifying therapy: Hydroxyurea, Voxelotor, L-Glutamine, or Crizanlizumab, for 3 months prior to enrollment will be eligible.

You may not qualify if:

• Current chronic transfusion therapy. Patients who received a simple transfusion for an acute event will be eligible 3 months after completion of transfusion
• Any contraindication to CMR such as metallic implants
• Inability to cooperate with CMR or echocardiography imaging
• Known congenital heart disease
• Estimated GFR ≤ to 30 mL/min/1.73 m2 by creatinine clearance
• Pregnant or lactating females or females of child-bearing potential who are unable to use a medically accepted form of contraception throughout the study
• Treatment with a renin-angiotensin pathway inhibitor during the 2 weeks prior to enrollment
• Hypersensitivity to angiotensin receptor II blockers
• Hyperkalemia (K\>5.5 mEq/L) on a non-hemolyzed sample despite low-potassium diet
• Hepatic dysfunction defined as serum ALT \> 5x the upper normal limit for age
• Current lithium therapy
• Chronic daily use of NSAID
• HIV infection.

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Losartan

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Central Study Contacts

Omar Niss, MD

CONTACT

(513) 803-7545; omar.niss@cchmc.org

Amanda Pfeiffer

CONTACT

(513) 803-4977; amanda.pfeiffer@cchmc.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2021
• First Posted: August 19, 2021
• Study Start: September 1, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)