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Losartan for Diffuse Myocardial Fibrosis in Sickle Cell Disease

Primary Purpose

Sickle Cell Disease, Diffuse Myocardial Fibrosis

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Losartan

About this trial

This is an interventional treatment trial for Sickle Cell Disease

Eligibility Criteria

6 Years - undefined (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Cincinnati Children's Hospital Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Losartan

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Change in Diastolic Function

Efficacy of losartan in improving diastolic function defined by echocardiographic and tissue Doppler assessment .

Change in Exercise Capacity

Efficacy of losartan in improving cardiopulmonary exercise testing (CPET) measurements.

Predicting Myocardial Fibrosis

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.

Full Information

NCT ID

NCT05012631

First Posted

July 15, 2021

Last Updated

March 9, 2023

Sponsor

Children's Hospital Medical Center, Cincinnati

1. Study Identification

Unique Protocol Identification Number

NCT05012631

Brief Title

Losartan for Diffuse Myocardial Fibrosis in Sickle Cell Disease

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Recruiting

Study Start Date

September 1, 2021 (Actual)

Primary Completion Date

December 31, 2023 (Anticipated)

Study Completion Date

December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Children's Hospital Medical Center, Cincinnati

4. Oversight

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

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sickle Cell Disease, Diffuse Myocardial Fibrosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Losartan

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Losartan

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Description

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

Time Frame

after 1 year of losartan treatment.

Secondary Outcome Measure Information:

Title

Change in Diastolic Function

Description

Efficacy of losartan in improving diastolic function defined by echocardiographic and tissue Doppler assessment .

Time Frame

after 1 year of losartan treatment.

Title

Change in Exercise Capacity

Description

Efficacy of losartan in improving cardiopulmonary exercise testing (CPET) measurements.

Time Frame

after 1 year of losartan treatment.

Title

Predicting Myocardial Fibrosis

Description

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.

Time Frame

At baseline and after one year of losartan treaement

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Omar Niss, MD

Phone

(513) 803-7545

omar.niss@cchmc.org

First Name & Middle Initial & Last Name or Official Title & Degree

Amanda Pfeiffer

Phone

(513) 803-4977

amanda.pfeiffer@cchmc.org

Facility Information:

Facility Name

Cincinnati Children's Hospital Medical Center

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45229

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Amanda Pfeiffer

Phone

513-803-4977

Amanda.Pfeiffer@cchmc.org

First Name & Middle Initial & Last Name & Degree

Amy Shova

Phone

(513)803-1917

Amy.Shova@cchmc.org

First Name & Middle Initial & Last Name & Degree

Omar Niss, MD

12. IPD Sharing Statement

Plan to Share IPD

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Losartan for Diffuse Myocardial Fibrosis in Sickle Cell Disease

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