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Losartan for Diffuse Myocardial Fibrosis in Sickle Cell Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05012631
Recruitment Status : Recruiting
First Posted : August 19, 2021
Last Update Posted : December 8, 2021
Sponsor:
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

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

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : September 1, 2021
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : December 31, 2024

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  1. Change in extracellular volume fraction (ECV) after 1 year of losartan treatment [ Time Frame: 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 :
  1. Change in Diastolic Function [ Time Frame: after 1 year of losartan treatment. ]
    Efficacy of losartan in improving diastolic function defined by echocardiographic and tissue Doppler assessment .

  2. Change in Exercise Capacity [ Time Frame: after 1 year of losartan treatment. ]
    Efficacy of losartan in improving cardiopulmonary exercise testing (CPET) measurements.

  3. Predicting Myocardial Fibrosis [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05012631


Contacts
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Contact: Omar Niss, MD (513) 803-7545 omar.niss@cchmc.org
Contact: Amanda Pfeiffer (513) 803-4977 amanda.pfeiffer@cchmc.org

Locations
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United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Amanda Pfeiffer    513-803-4977    Amanda.Pfeiffer@cchmc.org   
Contact: Amy Shova    (513)803-1917    Amy.Shova@cchmc.org   
Principal Investigator: Omar Niss, MD         
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
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Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT05012631    
Other Study ID Numbers: Losartan-CMR
First Posted: August 19, 2021    Key Record Dates
Last Update Posted: December 8, 2021
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Fibrosis
Pathologic Processes
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Losartan
Anti-Arrhythmia Agents
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action