Sickle Cell Disease
Conditions
Keywords
sickle cell disease, propanolol, red blood cell adhesion
Brief summary
Propanolol is a beta blocker which has been found to inhibit the ability of epinephrine to upregulate sickle red cell adhesion to laminin and endothelial cells in vitro. The purpose of this pilot study is to administer one dose of propanolol to children with sickle cell disease and to measure pre and post dose red cell adhesion. The hypothesis is that a single dose of propanolol will decrease red cell adhesion to laminin and endothelial cells as compared to baseline.
Detailed description
A similar pilot study has already been conducted in adults and is now being tried in children to gather preliminary data for a grant submission. No safety issues were found in the adult pilot study. This study will evaluate the effect of different doses of propanolol. The risks of this study involve the risks of three (3) blood draws and the risks of propanolol. In order to minimize the risks children with sickle cell disease and asthma will be excluded because asthma is a contraindication to the use of propanolol. In addition, patients will not be hypertensive or bradycardic.
Interventions
DRUGpropranolol
Propranolol hydrochloride is a synthetic beta-adrenergic receptor-blocking agent. This will be administered in an open-label single administration to 3 cohorts (10mg, 20mg, and 40mg) of children with sickle cell disease. Patient blood will be evaluated for red cell adhesion and patient data evaluated for safety monitoring.
Sponsors
Duke University
University of Miami
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. diagnosis of HbSS or HbSBeta0Thal 2. age 10-17 years 3. Weight 30kg or greater 4. Hb 7mg/dL or greater 5. informed consent
Exclusion criteria
1. History of vaso-occlusive crisis during the past 6 weeks, or history of transfusion during the past 3 months. 2. pregnancy 3. history of heart failure, myocardial infarction, asthma, bradyarrythmias, hypotension, thyroid disease, diabetes, renal insufficiency 4. concurrent medications: any antihypertensive medication, diuretics, thyroid replacement medications, any arrythmia medication, insulin, hypoglycaemic medication 5. history of allergy to sulfonamides 6. elevated BUN or creatinine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| measurement of the sickle red cell response to epinephrine | 1-4 weeks | At study initiation 5mL of blood is drawn to evaluate for red cell adhesion (screening visit or visit 1). At the intervention visit 1-4 weeks later another 5mL of blood will be drawn and patient will have an ECG performed, followed by one dose of propanolol at the stratum that s/he is in. Vitals signs will be monitored (including blood pressure) for 4 hours after drug administration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety data regarding the use of propanolol in children with sickle cell disease | within 24 hours after drug administration | 1. New onset wheezing 2. Onset of low blood pressure defined as blood pressure less than 90/50 3. Onset of heart rate less than 60 beats/min |
Countries
United States
Outcome results
None listed