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Preventing Sickle Cell Kidney Disease

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ClinicalTrials.gov Identifier: NCT02373241
Recruitment Status : Recruiting
First Posted : February 26, 2015
Last Update Posted : May 10, 2019
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Jeffrey D. Lebensburger, DO, University of Alabama at Birmingham

Tracking Information
First Submitted Date  ICMJE February 5, 2015
First Posted Date  ICMJE February 26, 2015
Last Update Posted Date May 10, 2019
Study Start Date  ICMJE April 2015
Estimated Primary Completion Date April 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 20, 2015)
Feasibility as measured by the number of patients that accept enrollment, remain adherent to losartan, and remain adherent to study procedures. [ Time Frame: 5 yrs ]
Outcome 1a. Document the rate of acceptance (quantitative) and reasons for acceptance/rejection (qualitative) in a randomized trial of trial of losartan for SCD patients with abnormal nocturnal blood pressures. Outcome 1b. Identify the adherence rate to losartan during a randomized three year trial of losartan for SCD patients (n=40) with abnormal nocturnal blood pressure. Outcome 1c. Determine the adherence rate to study procedures among participants enrolled in a three year trial of losartan for SCD patients (n=40) with abnormal nocturnal blood pressure.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 20, 2015)
  • Feasibility as measured by number of patients with adverse events to losartan. [ Time Frame: 5 yrs ]
    Participants will be randomized during this feasibility trial to either a standard BP lowering strategy (lower BP <95th percentile) vs intensive BP lowering strategy (lower BP <75th percentile). Losartan will be the anti-hypertensive therapy used in this feasibility trial. The number of adverse events on each arm will be monitored
  • To prospectively evaluate the incidence of hypertension (clinic and ambulatory) in patients with SCD and number of patients with abnormal blood pressure biomarkers. [ Time Frame: 5 yrs ]
    We will prospectively evaluate the incidence of hypertension (Clinic BP in pts >5yrs and ABPM in pts >10 yrs) and role of blood and urine biomarkers (pts >5ys) among participants with HbSS or SB0 thalassemia (expected cohort n=200) over 5 yrs
  • Feasibility as measured by the number of patients with improvement in nocturnal blood pressure while receiving losartan. [ Time Frame: 5 years ]
    As a feasibility trial, the effect of losartan on lowering nocturnal hypertension will be monitored to identify the difference in nocturnal BP improvement between the two treatment arms, and within group standard deviation of BP
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Preventing Sickle Cell Kidney Disease
Official Title  ICMJE Chronobiology and Chronopharmacology to Prevent Sickle Cell Kidney Disease
Brief Summary

Untreated hypertension and renal injury are risk factors for increased morbidity and mortality in sickle cell disease, yet early markers of progressive disease have not been identified and therapies to prevent the development of adverse cardiovascular outcomes have not been defined. Circadian blood pressure, as defined by 24 hour blood pressure monitoring, is more accurate than clinic blood pressure in defining secondary hypertension and abnormal nocturnal blood pressured dipping and nocturnal hypertension have been linked to progressive renal disease in other diseases.

Methodology/Aims: A randomized feasibility trial of losartan will be conducted among adolescent HbSS and SB0 thalassemia patients (11-19 years) with abnormal nocturnal blood pressure dipping. During this six month feasibility trial, two dosing strategies of losartan (titrated to keep clinic BP <95th percentile vs. <75th percentile) will be analyzed for safety and effect on restoring normal circadian blood pressure.

A prospective cohort study among HbSS and SB0 thalassemia patients (6-19 years) will also be conducted to evaluate the incidence of hypertension and role of monitoring potential biomarkers of kidney injury and hypertension. Cohort participants will undergo annual evaluations of hypertension(24 hour blood pressure monitoring for participants ≥ 11yrs, clinic BP in all participants) and markers of kidney injury/hypertension.

Expected Results: At the completion of the feasibility trial, vital background information will be obtained to design a definitive multicenter trial of hypertension in sickle cell disease. At the completion of the cohort study, the incidence of pediatric hypertension will be identified and the role for monitoring blood and urine biomarkers will be better understood.

As therapy for patients with renal failure is dismal, it is imperative that SCD patients at risk are identified early and that therapeutic trials are conducted that prevent progression.

Detailed Description

Feasibility Trial of Losartan to Correct Abnormal Circadian Blood Pressure. Cohort participants (below) identified with in-clinic hypertension and abnormal nocturnal dipping on 24 hour ABPM will be asked to participate in a feasibility trial of losartan. Participants will be offered a consultation with Pediatric Nephrology prior to study enrollment. Participants that consent /assent will undergo repeat 24 hour ABPM to confirm abnormal circadian blood pressure prior to receiving losartan. At baseline, participants will undergo evaluation for biomarkers of kidney injury and hypertension. Participants will start on losartan at 25mg of losartan and randomized to titrate clinic BP <95th or 75th percentile based on NHLBI BP tables. Participants will be followed monthly x 6 months and receive standard of care labs. ABPM and blood/urine biomarkers of kidney injury, buccal swab for circadian genes, and hypertension will be repeated at 3 and 6 months. Participants will undergo monthly evaluation for adherence through pill counting and questionnaires. Safety of dosing will be monitored by internal review and external review (DSMB).

Prospective Pediatric Cohort to Evaluate Hypertension and Kidney Injury. Patients with HbSS or SB0 thalassemia, ages ≥ 6 years and have signed informed consent will undergo clinic BP, annual ABPM and biomarkers to determine the incidence of HTN and potential role for biomarkers as monitors for the development of hypertension or kidney injury/disease. Urine will be collected annually and evaluated for current known biomarkers of kidney disease and stored for future analysis of relevant biomarkers. Uric acid will be processed from collected blood annually.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Anemia, Sickle Cell
  • Sickle Cell Disease
  • Kidney Disease
  • Hypertension
  • Proteinuria
Intervention  ICMJE
  • Drug: Losartan
    Standard dosing
    Other Name: coozar
  • Drug: Losartan
    Experimental dosing
    Other Name: coozar
Study Arms  ICMJE
  • Active Comparator: Standard Blood Pressure Management
    Participants initiated on 25mg of losartan daily and randomized to lower in-clinic BP to <95th percentile
    Intervention: Drug: Losartan
  • Experimental: Experimental Blood Pressure Management
    Participants initiated on 25mg of losartan daily and randomized to lower in-clinic BP to <75th percentile
    Intervention: Drug: Losartan
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 20, 2015)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2020
Estimated Primary Completion Date April 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Pts with HbSS or SB0 thalassemia
  • Hypertension from clinic BP readings (defined by NHLBI BP tables)
  • Abnormal nocturnal dipping (systolic or diastolic) as defined by <10% dip or abnormal nocturnal BP load (>25% of sleep BP readings >95th percentile as defined by AHA ABPM guidelines)
  • Signed Informed Consent

Exclusion Criteria:

  • Patient already on BP lowering medication
  • Hyperkalemia
  • Pregnancy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 5 Years to 25 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Jeffrey Lebensburger, DO, MSPH jlebensburger@peds.uab.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02373241
Other Study ID Numbers  ICMJE F141107009
1K23HL127100-01 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jeffrey D. Lebensburger, DO, University of Alabama at Birmingham
Study Sponsor  ICMJE University of Alabama at Birmingham
Collaborators  ICMJE National Heart, Lung, and Blood Institute (NHLBI)
Investigators  ICMJE
Principal Investigator: Jeffrey D Lebensburger, DO, MSPH University of Alabama at Birmingham
PRS Account University of Alabama at Birmingham
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP