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
About this trial
This is an interventional treatment trial for Sickle Cell Disease
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.
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
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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