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

NCT02012777 | Terminated Phase 1 DMC

• 1 other identifier: 20100334
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Sickle Cell Disease

Keywords

sickle cell disease; propanolol; red blood cell adhesion

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Safety data regarding the use of propanolol in children with sickle cell disease

  within 24 hours after drug administration

Study Arms (3)

cohort 1 10mg propranolol

ACTIVE COMPARATOR

first study arm will consist of 5 subjects who will be administered a dose of 10mg propanolol and followed 1-4 weeks. Data safety and monitoring committee has reviewed the data for safety and instructed the study to continue based on the findings.

Drug: propranolol

cohort 2 20mg propranolol

ACTIVE COMPARATOR

This cohort will involve the administration of 5 subjects with 20mg propanolol. The data safety and monitoring committee will review the data for safety when the 5 subjects are recruited and instruct the study to continue depending on the findings.

Drug: propranolol

cohort 3 40mg propranolol

ACTIVE COMPARATOR

This cohort will involve the administration of 10 subjects with 40mg propanolol. The data safety and monitoring committee will review the data for safety when the 10 subjects are recruited and instruct the study to continue depending on the findings.

Drug: propranolol

Interventions

propranolol DRUG

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.

Also known as: propanolol systemic, Inderal, Inderal LA, InnoPran XL

cohort 1 10mg propranolol; cohort 2 20mg propranolol; cohort 3 40mg propranolol

Eligibility Criteria

• Age: 10 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• diagnosis of HbSS or HbSBeta0Thal
• age 10-17 years
• Weight 30kg or greater
• Hb 7mg/dL or greater
• informed consent

You may not qualify if:

• History of vaso-occlusive crisis during the past 6 weeks, or history of transfusion during the past 3 months.
• pregnancy
• history of heart failure, myocardial infarction, asthma, bradyarrythmias, hypotension, thyroid disease, diabetes, renal insufficiency
• concurrent medications: any antihypertensive medication, diuretics, thyroid replacement medications, any arrythmia medication, insulin, hypoglycaemic medication
• history of allergy to sulfonamides
• elevated BUN or creatinine

Sponsors & Collaborators

• University of Miami: lead
• Duke University: collaborator

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

Location

Related Publications (9)

• 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.

  PMID: 20456345 BACKGROUND

• Leaute-Labreze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo JB, Taieb A. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008 Jun 12;358(24):2649-51. doi: 10.1056/NEJMc0708819. No abstract available.

  PMID: 18550886 RESULT

• 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.

  PMID: 19840322 RESULT

• 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.

  PMID: 20117846 RESULT

• Lamy S, Lachambre MP, Lord-Dufour S, Beliveau 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. Epub 2010 Aug 20.

  PMID: 20732454 RESULT

• 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.

  PMID: 20797926 RESULT

• 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.

  PMID: 20936416 RESULT

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

  RESULT

• 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.

  PMID: 20644039 RESULT

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Propranolol; propranolol CR

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Ofelia A Alvarez, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Clinical Pediatrics

Study Record Dates

• First Submitted: December 6, 2013
• First Posted: December 16, 2013
• Study Start: June 1, 2010
• Primary Completion: November 1, 2012
• Study Completion: April 3, 2013
• Last Updated: June 8, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will share

Locations

US (1)