Losartan for Sickle Cell Kidney Disease

NCT ID: NCT01989078

Last Updated: 2017-07-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2016-12-31

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.

Detailed Description

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. Losartan is an FDA-approved drug to treat blood pressure to protect the kidneys in people who have diseases like diabetes and blood pressure. It is not specifically labeled for use in sickle cell disease. Participants will be enrolled from Children's Healthcare of Atlanta (pediatric subjects) or Grady Memorial Hospital (adult subjects) and will be in the study for 1 to 2 years (depending on when the final renal function tests can be preformed).

The primary aim of this pilot study is to evaluate the acute and longer-term effects of losartan (study drug) on renal function in children and adults with SCD who have persistent albuminuria. The renal function tests will be done at study entry (prior to taking losartan), 1 month, and 1 to 2 years after starting losartan therapy. In addition, participants are assessed monthly by their regular clinical team. The second aim of this study is to assess the correlation of changes in albuminuria after 1 month of losartan with changes in direct measurements of renal 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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Losartan

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

Group Type: EXPERIMENTAL

Losartan

Intervention Type: 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.

Interventions

Losartan

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.

Intervention Type: DRUG

Other Intervention Names

Cozaar

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 9 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Marianne Yee, MD

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marianne Yee, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Grady Health Systems

Atlanta, Georgia, United States

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Countries

United States

Other Identifiers

IRB00056125

Identifier Type: -

Identifier Source: org_study_id