Losartan for Diffuse Myocardial Fibrosis in Sickle Cell Disease

Sickle Cell Disease Clinical Trial

Official title:

Losartan for Diffuse Myocardial Fibrosis in Sickle Cell Disease: A Prospective, Phase II Study.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05012631
• Other study ID #: Losartan-CMR
• Status: Recruiting
• Phase: Phase 2
• Start date: September 1, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: March 2023
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: Omar Niss, MD
• Phone: (513) 803-7545
• Email: omar.niss[@]cchmc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Years and older

Eligibility

Inclusion Criteria:

1. 6 years old or older

2. Diagnosis of HbSS or Sbeta0-thalassemia

3. Ability to cooperate with and undergo CMR without sedation or anesthesia

4. Ability to cooperate with and undergo echocardiogram without sedation or anesthesia

5. 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.

Exclusion Criteria:

1. Current chronic transfusion therapy. Patients who received a simple transfusion for an acute event will be eligible 3 months after completion of transfusion

2. SCD genotypes other than specified in inclusion criteria

3. Any contraindication to CMR such as metallic implants

4. Inability to cooperate with CMR or echocardiography imaging

5. Known congenital heart disease

6. Estimated GFR = to 30 mL/min/1.73 m2 by creatinine clearance

7. Pregnant or lactating females or females of child-bearing potential who are unable to use a medically accepted form of contraception throughout the study

8. Treatment with a renin-angiotensin pathway inhibitor during the 2 weeks prior to enrollment

9. Hypersensitivity to angiotensin receptor II blockers

10. Hyperkalemia (K>5.5 mEq/L) on a non-hemolyzed sample despite low-potassium diet

11. Hepatic dysfunction defined as serum ALT > 5x the upper normal limit for age

12. Current lithium therapy

13. Chronic daily use of NSAID

14. HIV infection.

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Fibrosis
• Sickle Cell Disease

Intervention

Drug:
• Losartan
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.

Locations

Country	Name	City	State
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change in Diastolic Function	Efficacy of losartan in improving diastolic function defined by echocardiographic and tissue Doppler assessment .	after 1 year of losartan treatment.
Secondary	Change in Exercise Capacity	Efficacy of losartan in improving cardiopulmonary exercise testing (CPET) measurements.	after 1 year of losartan treatment.
Secondary	Predicting Myocardial Fibrosis	Explore the performance characteristics of the following serum biomarkers in predicting myocardial fibrosis in patients with SCD: PICP, PIIINP, TGF-ß, CTGF, soluble ST2, galectin-3, and NT-proBNP.	At baseline and after one year of losartan treaement