Sickle Cell DiseaseEarly Phase 1SCD-LosartanNCT01989078
Losartan for Sickle Cell Kidney Disease
A Early Phase 1 study testing Losartan in people with Sickle Cell Disease, run by Emory University at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 9 years and older
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Losartan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 2 sitesUnited States
- Study dates
- Dec 2012to Dec 2016
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 9 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Grady Health Systems
Atlanta, Georgia, 30303
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
About this study
Official title: Losartan Treatment for Sickle Cell Chronic Kidney Disease
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.
Read the 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
- Being tested
- Losartan
- Keywords
- Kidney disorder, Blood disorder, Pediatrics
- Medical subject headings
- Anemia, Sickle Cell, Kidney Diseases, Hematologic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LosartanDrug
Also called Cozaar
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.
| Study group | Role | What they receive |
|---|---|---|
| Losartan | Experimental | Participants taking losartan, in addition to taking hydroxyurea therapy, as prescribed per standard of care Receives: Drug: Losartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in albumin/creatinine ratio (ACR)
The effects of losartan on the mean change in albumin/creatinine ratio (ACR) will be examined.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, Month 1, End of treatment (12 to 24 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2013 (estimated)
- Study startDec 2012
- Primary completionDec 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Participants will all receive the study medication in addition to the standard of care treatment. There is no control group for this pilot study.
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marianne Yee, MD, Emory University
- Investigators
- Marianne Yee, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01989078
- Sponsor's protocol ID
- IRB00056125
- Acronym
- SCD-Losartan
- Status last verified
- Jul 2017
- First submitted
- 26 Feb 2013
- Last updated
- 17 Jul 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Losartan Treatment for Sickle Cell Chronic Kidney Disease
- ClinicalTrials.gov ID
- NCT01989078
- Acronym / sponsor ID
- SCD-Losartan / IRB00056125
- Conditions
- Sickle Cell Disease
- Keywords
- Kidney disorder, Blood disorder, Pediatrics
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Study start
- Dec 2012
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 20 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Participants will all receive the study medication in addition to the standard of care treatment. There is no control group for this pilot study.
| Arm | Type | Receives |
|---|---|---|
| Losartan | Experimental | Drug: LosartanParticipants taking losartan, in addition to taking hydroxyurea therapy, as prescribed per standard of care |
Who may qualify
- Ages
- 9 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (6 listed)
- 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))
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LosartanAlso: CozaarAdults 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. | Drug | Losartan |
Primary outcome
Change in albumin/creatinine ratio (ACR)
Time frame: Baseline, Month 1, End of treatment (12 to 24 months)
The effects of losartan on the mean change in albumin/creatinine ratio (ACR) will be examined.
Change in glomerular filtration rate (GFR)
Time frame: Baseline, Month 1, End of treatment (12 to 24 months)
The effects of losartan on the mean change in glomerular filtration rate (GFR) will be examined.
Change in renal plasma flow (RPF)
Time frame: Baseline, Month 1, End of treatment (12 to 24 months)
The effects of losartan on the mean change in renal plasma flow (RPF) will be examined.
Change in glomerular permeability (GP)
Time frame: Baseline, Month 1, End of treatment (12 to 24 months)
The effects of losartan on the mean change in glomerular permeability (GP) will be examined.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marianne Yee, MD principal investigator
Emory University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Losartan in people with Sickle Cell Disease, run by Emory University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in albumin/creatinine ratio (ACR) (time frame: Baseline, Month 1, End of treatment (12 to 24 months)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2017.