Losartan to Reverse Sickle Nephropathy

This study is currently recruiting participants.
Verified April 2014 by Children's Hospital Medical Center, Cincinnati
Sponsor:
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier:
NCT01479439
First received: November 16, 2011
Last updated: April 8, 2014
Last verified: April 2014
  Purpose

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. 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.


Condition Intervention Phase
Nephropathy
Sickle Cell Anemia
Drug: Losartan
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
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. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    A significant association of creatinine clearance with cystatin C estimated GFR


Estimated Enrollment: 54
Study Start Date: February 2012
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: December 2014 (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

  Eligibility

Ages Eligible for Study:   6 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01479439

Contacts
Contact: Tamara Nordheim, RN 513-636-7374 tamara.nordheim@cchmc.org

Locations
United States, Illinois
University of Illinois at Chicago Recruiting
Chicago, Illinois, United States, 60612
Contact: Lani Krauz, BSN,RN       lignacio@uic.edu   
Principal Investigator: Victor Gordeuk, MD         
United States, Kentucky
University of Louisville Recruiting
Louisville, Kentucky, United States
Contact: Tressa Bratton       tressa.bratton@louisville.edu   
Principal Investigator: Ashok Raj, M.D.         
United States, Ohio
Akron Children's Hospital Recruiting
Akron, Ohio, United States, 44308
Contact: Felicia Lewis, BS, CCRC       flewis2@chmca.org   
Principal Investigator: Prasad Bodas, MD         
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Tamara Nordheim       tamara.nordheim@cchmc.org   
Principal Investigator: Charles Quinn, M.D.         
University of Cincinnati Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Tamara Nordheim       tamara.nordheim@cchmc.org   
Principal Investigator: George Atweh, M.D.         
Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43205
Contact: Heidi Ziegler       heidi.ziegler@nationwidechildrens.org   
Principal Investigator: Susan Creary, M.D.         
Ohio State University Recruiting
Columbus, Ohio, United States
Contact: Leslie Witkoff       leslie.witkoff@osumc.edu   
Principal Investigator: Eric Kraut, M.D.         
United States, Texas
University of Texas Southwestern Recruiting
Dallas, Texas, United States, 75390
Contact: Pamela Kurian, MS       pamela.kurian@utsouthwestern.edu   
Principal Investigator: Alecia Nero, MD         
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Investigators
Principal Investigator: Punam Malik, M.D. Children's Hospital Medical Center, Cincinnati
  More Information

No publications provided

Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT01479439     History of Changes
Other Study ID Numbers: 2010-3070
Study First Received: November 16, 2011
Last Updated: April 8, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Anemia
Anemia, Sickle Cell
Kidney Diseases
Hematologic Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hemoglobinopathies
Genetic Diseases, Inborn
Urologic Diseases
Losartan
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 14, 2014