Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

Losartan to Reverse Sickle Nephropathy

This study has been completed.
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati Identifier:
First received: November 16, 2011
Last updated: November 28, 2016
Last verified: November 2016
Sickle cell disease causes kidney damage with increasing age, leading to chronic kidney disease and renal failure in nearly one third of patients with sickle cell disease. Currently, there is no treatment for sickle cell related kidney disease.

Condition Intervention Phase
Sickle Cell Anemia
Drug: Losartan
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Losartan to Reverse Sickle Nephropathy

Resource links provided by NLM:

Further study details as provided by Children's Hospital Medical Center, Cincinnati:

Primary Outcome Measures:
  • Changes from baseline albuminuria [ Time Frame: Assessed at weeks 2, 4, 8, 12, and 26. ]
    A ≥25% reduction in urine albumin from baseline in ≥ 30% of the subjects in the MiA group.

Secondary Outcome Measures:
  • Change from baseline in urine osmolality [ Time Frame: Assessed at weeks 12 and 26. ]
    A significant improvement in UOsm in the NoA group.

  • No changes in category of albuminuria (NoA, MiA or MaA) [ Time Frame: Assessed at weeks 2, 4, 8, 12, and 26 ]
    It is likely that the intervention may halt the progression of NoA to MiA or MiA to MaA, and albuminuria would have worsened if there was no intervention. Therefore, the hypothesis is that there will be no change in the category of albuminuria.

  • Identification of novel biomarkers [ Time Frame: Assessed at baseline and weeks 4, 12, and 26 ]
    A significant association of KIM-1 and NAG biomarkers with renal function (albuminuria and UCD).

  • Serum Cystatin C [ Time Frame: Assessed at screening, baseline and weeks and weeks 2, 4, 8, 12, and 26 ]
    A significant association of creatinine clearance with cystatin C estimated GFR

Enrollment: 36
Study Start Date: February 2012
Study Completion Date: December 2015
Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sickle cell disease
The purpose of this research study is to see if losartan can help reduce or reverse damage done to the kidneys of children and adults with Sickle Cell Anemia (SCA) and Sickle Beta-zero (HbSβ0) Thalassemia.
Drug: Losartan
Form: suspension, tablet. Dosage & frequency: age 6-16 = 0.7mg/kg once daily; age >16 = 50mg once daily. Duration: 6 months

Detailed Description:
The purpose of this research study is to see if losartan can help reduce or reverse damage done to the kidneys of children and adults with Sickle Cell Anemia (SCA) and Sickle Beta-zero (HbSβ0) Thalassemia.

Ages Eligible for Study:   6 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Age ≥6 years of age; for no albuminuria (NoA) group age is ≥ 6 years and <21 years of age
  2. Diagnosis of hemoglobin SS disease or Sβ0 thalassemia by hemoglobin electrophoresis and/or β-globin gene mapping.
  3. Urine osmolality <700 mOsm on first morning urine
  4. Written informed consent (and assent, where applicable)
  5. Documented urine albumin levels showing either

    • NoA:,.UAlb <30mg/g creatinine on a first morning urine
    • MiA: UAlb 30-300 mg/g creatinine on a first morning urine or
    • MaA: UAlb >300 mg/g creatinine on a first morning urine sample
  6. A documented negative serum pregnancy test for females with child bearing potential or greater than 10 years of age within (prior to) 7 days of starting the study medication.
  7. Subjects with child-bearing potential must be willing to use a medically accepted form of contraception throughout the study.
  8. Patients on hydroxyurea who are on a stable (not changing) dose of HU for three months prior to study entry.

Exclusion Criteria:

  1. Patients with Hb SC, SD, Sβ+thal, SE and other sickle hemoglobinopathies, and sickle trait (AS).
  2. Pregnant or lactating females, or females of child-bearing potential that are unable to use a medically accepted form of contraception throughout the study.
  3. Urine creatinine clearance (Clcr) <60 mL/minute/1.73 m2
  4. Gross (not microscopic) hematuria. If hematuria has resolved for 2 weeks or more, patients will be eligible.
  5. Hyperkalemia (K≥5.5) at baseline despite a low potassium diet
  6. Concurrent condition that predisposes to nephropathy, such as lupus, diabetes, and hypertension, not controlled with medications..
  7. On a renin-angiotensin pathway inhibitor (e.g., captopril, lisinopril, Losartan, valsartan, etc) for the last two weeks prior to enrollment.
  8. Hypersensitivity to Angiotensin II receptor blockers such as losartan, valsartan, telmisartan.
  9. Patients on red cell apheresis or ongoing aggressive chronic transfusions (one or more a month with a goal of HbS < 30%). Patients receiving a simple transfusion for symptoms during acute event will be eligible, but if they receive a partial or full exchange transfusion during an acute event, then they will only be eligible after 90 days.
  10. Hepatic dysfunction defined as ALT or direct bilirubin > 3X upper limit of normal (ULN).
  11. Chronic therapy with NSAIDS or Cox2 inhibitors
  12. On another interventional trial. May be eligible two weeks after completion of another interventional study.
  13. Any condition that interferes with the ability of the patient to understand or comply with the treatment plan and follow up.
  14. A serious mental or physical illness or a major disease (cardiac, renal, hepatic, neurological, endocrine, metabolic, pulmonary function or psychiatric), which in the opinion of the investigator would compromise participation in the study.
  15. Unable to take oral medications.
  16. HIV confirmed positive.
  17. Chronic therapy with steroids. May be eligible after three weeks of completing steroid therapy.
  18. Patients on lithium will be excluded
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01479439

United States, Illinois
University of Illinois at Chicago
Chicago, Illinois, United States, 60612
United States, Kentucky
University of Louisville
Louisville, Kentucky, United States, 40201
United States, Maryland
Bethesda, Maryland, United States, 20892
United States, Ohio
Akron Children's Hospital
Akron, Ohio, United States, 44308
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
University of Cincinnati
Cincinnati, Ohio, United States, 45229
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Texas
University of Texas Southwestern
Dallas, Texas, United States, 75390
Texas Children's Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Principal Investigator: Punam Malik, M.D. Children's Hospital Medical Center, Cincinnati
  More Information

Responsible Party: Children's Hospital Medical Center, Cincinnati Identifier: NCT01479439     History of Changes
Other Study ID Numbers: 2010-3070
Study First Received: November 16, 2011
Last Updated: November 28, 2016
Individual Participant Data  
Plan to Share IPD: No

Additional relevant MeSH terms:
Kidney Diseases
Anemia, Sickle Cell
Urologic Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hematologic Diseases
Genetic Diseases, Inborn
Anti-Arrhythmia Agents
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action processed this record on May 25, 2017