Losartan to Reverse Sickle Nephropathy

Sickle Cell Anemia Clinical Trial

Official title:

A Phase II Trial of Losartan to Reverse Sickle Nephropathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01479439
• Other study ID #: 2010-3070
• Status: Completed
• Phase: Phase 2
• Start date: February 2012
• Est. completion date: December 2015

Study information

• Verified date: September 2020
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: December 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

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 Sß0 thalassemia by hemoglobin electrophoresis and/or ß-globin gene mapping.

3. Urine osmolality <700 mOsm (milliosmoles) on first morning urine

4. Written informed consent (and assent, where applicable)

5. Documented urine albumin to creatinine ratio (UACR) showing either

• NoA: UACR <30mg/g creatinine on a first morning urine

• MiA: UACR 30-300 mg/g creatinine on a first morning urine or

• MaA: UACR >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 (HU) 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, Sß+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 (alanine aminotransferase) or direct bilirubin > 3-times 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

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Kidney Diseases
• Nephropathy
• Sickle Cell Anemia

Intervention

Drug:
• Losartan
Form: suspension, tablet. Dosage & frequency: age 6-16 = 0.7mg/kg once daily; age >16 = 50mg once daily. Duration: 6 months

Locations

Country	Name	City	State
United States	Akron Children's Hospital	Akron	Ohio
United States	NHLBI	Bethesda	Maryland
United States	University of Illinois at Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	University of Cincinnati	Cincinnati	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	University of Texas Southwestern	Dallas	Texas
United States	Texas Children's Hospital	Houston	Texas
United States	University of Louisville	Louisville	Kentucky

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati

Country where clinical trial is conducted

United States, 

References & Publications (1)

Quinn CT, Saraf SL, Gordeuk VR, Fitzhugh CD, Creary SE, Bodas P, George A, Raj AB, Nero AC, Terrell CE, McCord L, Lane A, Ackerman HC, Yang Y, Niss O, Taylor MD, Devarajan P, Malik P. Losartan for the nephropathy of sickle cell anemia: A phase-2, multicen — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Categorical Change in Urinary Albumin-to-creatinine Ratio (UACR) From Baseline	Number of participants who have a =25% reduction in urinary albumin-to-creatinine ratio (UACR) from baseline to 6 months. This is a categorical outcome (yes/no).; We hypothesized and pre-specified that =30% of the subjects in the microalbuminuria group would meet this outcome.	Baseline and 6 months
Secondary	Change in UACR	Fold-change in UACR from baseline	Baseline and 6 months
Secondary	Change in Creatinine Clearance	Fold-change in creatinine clearance by 24h urine collection (GFR-CrCl) from baseline	Baseline and 6 months

External Links

•   Journal Site