Losartan for Sickle Cell Kidney Disease

NCT01989078 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: IRB00056125
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

Sickle cell nephropathy (SCN) is a progressive complication of sickle cell disease (SCD) that begins in childhood and results in renal (kidney) failure and early mortality in nearly 12% of adults with hemoglobin SS (HbSS). The potential for prevention and reversal of kidney damage in SCD is not known. Albuminuria is a commonly used biomarker of glomerular damage; however the correlations of albuminuria with specific measurements of glomerular function and pathophysiology have not been determined. The investigators hypothesize that in patients with persistent albuminuria despite treatment of SCD with hydroxyurea, losartan will reverse kidney dysfunction in early stage nephropathy and ameliorate progressive kidney dysfunction in more advanced nephropathy. The primary aim is to study the acute and longer-term effects of losartan (study drug) on specific glomerular functions in children and adults with SCD who have persistent albuminuria. Research glomerular function tests will be done at study entry (prior to taking losartan), 1 month, and 1 to 2 years after starting losartan therapy (participants may take losartan for up to 24 months). In addition, participants are seen each month in clinic and assessed by their regular clinical team. The second aim is to assess the correlation of changes in albuminuria after 1 month of losartan with changes in direct measurements of glomerular function at 12-24 months, thus determining if the magnitude of the initial decrease in albuminuria in response to losartan predicts sustained improvements in renal function.

Conditions

Sickle Cell Disease

Keywords

Kidney disorder; Blood disorder; Pediatrics

Outcome Measures

Primary Outcomes (4)

• Change in albumin/creatinine ratio (ACR)

  The effects of losartan on the mean change in albumin/creatinine ratio (ACR) will be examined.

  Baseline, Month 1, End of treatment (12 to 24 months)

• Change in glomerular filtration rate (GFR)

  The effects of losartan on the mean change in glomerular filtration rate (GFR) will be examined.

  Baseline, Month 1, End of treatment (12 to 24 months)

• Change in renal plasma flow (RPF)

  The effects of losartan on the mean change in renal plasma flow (RPF) will be examined.

  Baseline, Month 1, End of treatment (12 to 24 months)

• Change in glomerular permeability (GP)

  The effects of losartan on the mean change in glomerular permeability (GP) will be examined.

  Baseline, Month 1, End of treatment (12 to 24 months)

Other Outcomes (3)

• Association between changes in albumin/creatinine ratio (ACR) at one month and glomerular filtration rate (GFR) at 12 months

  Baseline, Month 1, End of treatment (12 to 24 months)

• Association between changes in albumin/creatinine ratio (ACR) at one month and renal plasma flow (RPF) at 12 months

  Baseline, Month 1, End of treatment (12 to 24 months)

• Association between changes in albumin/creatinine ratio (ACR) at one month and glomerular permeability (GP) at 12 months

  Baseline, Month 1, End of treatment (12 to 24 months)

Study Arms (1)

Losartan

EXPERIMENTAL

Participants taking losartan, in addition to taking hydroxyurea therapy, as prescribed per standard of care

Drug: Losartan

Interventions

Losartan DRUG

Adults and Children \>50 kg: * Those with systolic blood pressure (SBP) ≥ 100 mm Hg at entry will start with 50 mg of oral losartan once daily. At the week 2 visit, losartan will be increased to 100 mg daily. * Those with SBP \<100 mm Hg at entry will start with 25 mg of oral losartan once daily. Participants will return after 1 week for titration to 50 mg daily, if tolerated (i.e. SBP not lower than pre-losartan measurement by 10 mm Hg or more), and after 2 weeks to monitor blood pressure. Children \<50 kg weight: * Treatment will start with 25 mg oral Losartan once daily given as a morning dose. At the 2 week visit, Losartan will be increased to 50 mg daily. The dose will be increased to 100 mg once a body weight of 50 kg is achieved.

Also known as: Cozaar

Losartan

Eligibility Criteria

• Age: 9 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• SCD genotype HbSS or HbS/beta-0-thalassemia
• Age greater than or equal to 9 years old
• Urinary albumin/creatinine ratio (ACR) greater than or equal to 30 mg/gram creatinine on greater than or equal to 2 occasions separated by one month or more
• Current treatment with hydroxyurea and a sustained hematologic response for 6 months or more prior to enrollment

You may not qualify if:

• End-stage renal failure (estimated GFR \<30 ml/min/1.73 m2)
• Known co-existent medical conditions that could affect the kidneys, such as diabetes mellitus, systemic lupus erythematosus (SLE), or human immunodeficiency virus (HIV) positive
• Chronic therapy (daily use for ≥8 weeks) with non-steroidal anti-inflammatory drugs (NSAIDs)
• Females who are pregnant
• Pre-existing hyperkalemia (serum potassium \> 5.5 milliequivalents per liter (mEq/L))
• Current chronic transfusion therapy

Sponsors & Collaborators

• Emory University: lead

Study Sites (2)

Grady Health Systems

Atlanta, Georgia, 30303, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Anemia, Sickle Cell; Kidney Diseases; Hematologic Diseases

Interventions

Losartan

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Study Officials

• Marianne Yee, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Participants will all receive the study medication in addition to the standard of care treatment. There is no control group for this pilot study.

Study Record Dates

• First Submitted: February 26, 2013
• First Posted: November 20, 2013
• Study Start: December 1, 2012
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: July 17, 2017

Record last verified: 2017-07

Locations

US (2)