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

NCT ID: NCT02012777

Last Updated: 2017-06-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30
• Study Completion Date: 2013-04-03

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.

Conditions

Sickle Cell Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

cohort 1 10mg propranolol

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.

Group Type: ACTIVE_COMPARATOR

propranolol

Intervention Type: 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.

cohort 2 20mg propranolol

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.

Group Type: ACTIVE_COMPARATOR

propranolol

Intervention Type: 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.

cohort 3 40mg propranolol

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.

Group Type: ACTIVE_COMPARATOR

propranolol

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

propanolol systemic; Inderal; Inderal LA; InnoPran XL

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

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Duke University

OTHER

Sponsor Role: collaborator

University of Miami

OTHER

Sponsor Role: lead

Responsible Party

Ofelia Alvarez

Professor of Clinical Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ofelia A Alvarez, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

University of Miami

Miami, Florida, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 20456345 (View on PubMed)

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.

Reference Type: RESULT

PMID: 18550886 (View on PubMed)

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.

Reference Type: RESULT

PMID: 19840322 (View on PubMed)

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.

Reference Type: RESULT

PMID: 20117846 (View on PubMed)

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.

Reference Type: RESULT

PMID: 20732454 (View on PubMed)

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.

Reference Type: RESULT

PMID: 20797926 (View on PubMed)

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.

Reference Type: RESULT

PMID: 20936416 (View on PubMed)

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

Reference Type: 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.

Reference Type: RESULT

PMID: 20644039 (View on PubMed)

Other Identifiers

20100334

Identifier Type: -

Identifier Source: org_study_id