Chronobiology and Chronopharmacology to Prevent Sickle Cell Kidney Disease

Locations

1 United States site

Age

5 to 25 Years

Genotypes

HbSS

Phase

Phase 2

Study type

Interventional

Gender

All

Interventions

Drug

Compensation

Unknown

About the study

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.

participation requirements

– 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

participation restrictions

– Patient already on BP lowering medication

– Hyperkalemia

– Pregnancy

Locations

  • Birmingham, Alabama, United States, University of Alabama at Birmingham, 35223