Clinical trial NCT02012777: Propanolol and Red Cell Adhesion Non-asthmatic Children Sickle Cell Disease
Official title: Propanolol Effect on Red Cell Adhesion in Non-Asthmatic Children With Sickle Cell Disease: A Dose Finding Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Sickle Cell Disease
Keywords: sickle cell disease
propanolol
red blood cell adhesion
Lead sponsor: University of Miami
Sponsor class: OTHER
Collaborators: name: Duke University
First posted: 2013-12-16
Enrollment: 9
Sex: ALL
Minimum age (years): 10
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: measurement of the sickle red cell response to epinephrine
timeFrame: 1-4 weeks
Secondary outcomes:
measure: Safety data regarding the use of propanolol in children with sickle cell disease
timeFrame: within 24 hours after drug administration
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
Study officials:
affiliation: University of Miami
name: Ofelia A Alvarez, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Lawley LP, Siegfried E, Todd JL. Propranolol treatment for hemangioma of infancy: risks and recommendations. Pediatr Dermatol. 2009 Sep-Oct;26(5):610-4. doi: 10.1111/j.1525-1470.2009.00975.x.
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citation: Holmes WJ, Mishra A, Gorst C, Liew SH. Propranolol as first-line treatment for rapidly proliferating infantile haemangiomas. J Plast Reconstr Aesthet Surg. 2011 Apr;64(4):445-51. doi: 10.1016/j.bjps.2010.07.009. Epub 2010 Aug 24.
citation: Schiestl C, Neuhaus K, Zoller S, Subotic U, Forster-Kuebler I, Michels R, Balmer C, Weibel L. Efficacy and safety of propranolol as first-line treatment for infantile hemangiomas. Eur J Pediatr. 2011 Apr;170(4):493-501. doi: 10.1007/s00431-010-1324-2. Epub 2010 Oct 9.
citation: Chang, MW. Journal Watch Dermatology. Nov 6, 2009 Propanolol for Infantile Hemangioma: Safety Issues and Proposed Protocol
citation: Holland KE, Frieden IJ, Frommelt PC, Mancini AJ, Wyatt D, Drolet BA. Hypoglycemia in children taking propranolol for the treatment of infantile hemangioma. Arch Dermatol. 2010 Jul;146(7):775-8. doi: 10.1001/archdermatol.2010.158.