Losartan for Diffuse Myocardial Fibrosis in Sickle Cell Disease

Sponsor

Children's Hospital Medical Center, Cincinnati (Other)

Overall Status

Recruiting

CT.gov ID

NCT05012631

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Sickle Cell Disease Diffuse Myocardial Fibrosis	Drug: Losartan	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 1, 2021

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Losartan 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 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.

Arm

Intervention/Treatment

Experimental: Losartan

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

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.

Outcome Measures

Primary Outcome Measures

Change in extracellular volume fraction (ECV) after 1 year of losartan treatment [after 1 year of losartan treatment.]
Efficacy of losartan in stabilizing or reducing ECV (diffuse myocardial fibrosis) in SCD after one year.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

6 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.

Exclusion Criteria:

Current chronic transfusion therapy. Patients who received a simple transfusion for an acute event will be eligible 3 months after completion of transfusion
SCD genotypes other than specified in inclusion criteria
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229

Sponsors and Collaborators

Children's Hospital Medical Center, Cincinnati

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Children's Hospital Medical Center, Cincinnati

ClinicalTrials.gov Identifier:

NCT05012631

Other Study ID Numbers:

Losartan-CMR

First Posted:

Aug 19, 2021

Last Update Posted:

Dec 8, 2021

Last Verified:

Dec 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Additional relevant MeSH terms:

Anemia, Sickle Cell

Fibrosis

Losartan

Study Results

No Results Posted as of Dec 8, 2021