A Phase II Trial of Losartan to Reverse Sickle Nephropathy

Study ID
STU 012013-064

Cancer Related
No

Healthy Volunteers
No

Study Sites

  • UT Southwestern Ambulatory Services
  • UT Southwestern University Hospital—St. Paul
  • UT Southwestern University Hospital– Zale Lipshy
  • Parkland Health & Hospital System

Contact
Isabel Villalobos
214-648-7010
isabel.villalobos@utsouthwestern.edu

Principal Investigator
Alecia Nero

Summary

although the protocol states that there will be children enrolled on this study, this site will not be recruiting children.

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 adults with Sickle Cell anemia (SCa) and Sickle Beta-zero (HbS[MiCRo-SYMBoL]0) Thalassemia.

Subjects will be started on 50 mg administered once daily. if no improvement in albuminuria is seen in two weeks, the dose may be increased to 75 mg/day, and then to 100mg/day two weeks apart. The 100mg/day dose may be given in two divided doses (twice daily). The maximum total daily dosage of losartan is 100 mg/day.

Based on these results, patients will be classified into two groups for a 6 month treatment with losartan:

1)uCD, noa: This group will comprise of patients with tubular dysfunction (manifest as uCD) (n[?]14). uCD, noa is defined as uosm [Less Than]700, ualb [Less Than]30mg/g creatinine.
2) uCD, Mia: This group will comprise of patients with early glomerulopathy (Mia) and tubulopathy (n[?]14). uCD Mia is defined as uosm [Less Than]700, ualb 30-300 mg/g creatinine. We hypothesize that losartan will reduce or revert Mia by [GreaterThanorequalTo]25%, and may improve uCD.
3) uCD, Maa: This group will comprise of patients with overt glomerulopathy, with high risk of progressing to eSRD (n[?]8). uCD Maa is defined as uosm [Less Than]700, ualb [Greater Than]300 mg/g crt. We hypothesize that losartan will reduce the albuminuria by [GreaterThanorequalTo]25%.
all patients will undergo an echo, 6 minute walk test and have plasma nT-pro-BnP measured before and after 6 months of losartan to assess for improvement in cardiopulmonary function.

Primary endpoint:
a [GreaterThanorequalTo]25% reduction in urine albumin from baseline in [GreaterThanorequalTo] 30% of the subjects in the Mia group.


Secondary endpoints:
1. a significant improvement in uosm in the noa group.
2. Category of albuminuria (noa, Mia or Maa). 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.
3. a significant association of KiM-1 and naG biomarkers with renal function
(albuminuria and uCD).
4. a significant association of creatinine clearance with cystatin C estimated GFR.

Participant Eligibility

1. Diagnosis of hemoglobin SS disease or S[BETA]0 thalassemia by hemoglobin electrophoresis and/or [BETA]-globin gene mapping.
2. Urine osmolality <700 mOsm on first morning urine
3. Written informed consent (and assent, where applicable)
4. 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.