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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
Sponsored by
Children's Hospital Medical Center, Cincinnati
About
Eligibility
Locations
Arms
Outcomes
Full info

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:

  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.

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

First Posted
July 15, 2021
Last Updated
March 9, 2023
Sponsor
Children's Hospital Medical Center, Cincinnati
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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
No
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
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
Email
omar.niss@cchmc.org
First Name & Middle Initial & Last Name or Official Title & Degree
Amanda Pfeiffer
Phone
(513) 803-4977
Email
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
Email
Amanda.Pfeiffer@cchmc.org
First Name & Middle Initial & Last Name & Degree
Amy Shova
Phone
(513)803-1917
Email
Amy.Shova@cchmc.org
First Name & Middle Initial & Last Name & Degree
Omar Niss, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Losartan for Diffuse Myocardial Fibrosis in Sickle Cell Disease

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