Propanolol and Red Cell Adhesion Non-asthmatic Children Sickle Cell Disease

Sickle Cell Disease Clinical Trial

Official title:

Propanolol Effect on Red Cell Adhesion in Non-Asthmatic Children With Sickle Cell Disease: A Dose Finding Study

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02012777
• Other study ID #: 20100334
• Status: Terminated
• Phase: Phase 1
• First received: December 6, 2013
• Last updated: June 6, 2017
• Start date: June 2010
• Est. completion date: April 3, 2013

Study information

• Verified date: June 2017
• Source: University of Miami
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: April 3, 2013
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease
• Tissue Adhesions

Intervention

Drug:
• propranolol
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.

Locations

Country	Name	City	State
United States	University of Miami	Miami	Florida

Sponsors (2)

Lead Sponsor	Collaborator
University of Miami	Duke University

Country where clinical trial is conducted

United States, 

References & Publications (9)

Chang, MW. Journal Watch Dermatology. Nov 6, 2009 Propanolol for Infantile Hemangioma: Safety Issues and Proposed Protocol

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. — View 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. — View Citation

Lamy S, Lachambre MP, Lord-Dufour S, Béliveau R. Propranolol suppresses angiogenesis in vitro: inhibition of proliferation, migration, and differentiation of endothelial cells. Vascul Pharmacol. 2010 Nov-Dec;53(5-6):200-8. doi: 10.1016/j.vph.2010.08.002. — View 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. — View Citation

Léauté-Labrèze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo JB, Taïeb A. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008 Jun 12;358(24):2649-51. doi: 10.1056/NEJMc0708819. — View 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. Epu — View Citation

Storch CH, Hoeger PH. Propranolol for infantile haemangiomas: insights into the molecular mechanisms of action. Br J Dermatol. 2010 Aug;163(2):269-74. doi: 10.1111/j.1365-2133.2010.09848.x. Epub 2010 May 8. Review. — View Citation

Zimmermann AP, Wiegand S, Werner JA, Eivazi B. Propranolol therapy for infantile haemangiomas: review of the literature. Int J Pediatr Otorhinolaryngol. 2010 Apr;74(4):338-42. doi: 10.1016/j.ijporl.2010.01.001. Epub 2010 Feb 1. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	measurement of the sickle red cell response to epinephrine	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.	1-4 weeks
Secondary	Safety data regarding the use of propanolol in children with sickle cell disease	New onset wheezing; Onset of low blood pressure defined as blood pressure less than 90/50; Onset of heart rate less than 60 beats/min	within 24 hours after drug administration