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

Primary Purpose

Sickle Cell Disease

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

propranolol

About this trial

This is an interventional treatment trial for Sickle Cell Disease focused on measuring sickle cell disease, propanolol, red blood cell adhesion

Eligibility Criteria

10 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

University of Miami

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Arm Label

cohort 1 10mg propranolol

cohort 2 20mg propranolol

cohort 3 40mg propranolol

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

NCT ID

NCT02012777

First Posted

December 6, 2013

Last Updated

June 6, 2017

Sponsor

University of Miami

Collaborators

Duke University

1. Study Identification

Unique Protocol Identification Number

NCT02012777

Brief Title

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

2. Study Status

Record Verification Date

June 2017

Overall Recruitment Status

Terminated

Why Stopped

Inability to recruit patients into the study.

Study Start Date

June 2010 (undefined)

Primary Completion Date

November 2012 (Actual)

Study Completion Date

April 3, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Miami

Collaborators

Duke University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sickle Cell Disease

Keywords

sickle cell disease, propanolol, red blood cell adhesion

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

cohort 1 10mg propranolol

Arm Type

Active Comparator

Arm Description

Arm Title

cohort 2 20mg propranolol

Arm Type

Active Comparator

Arm Description

Arm Title

cohort 3 40mg propranolol

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

propranolol

Other Intervention Name(s)

propanolol systemic, Inderal, Inderal LA, InnoPran XL

Intervention Description

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.

Primary Outcome Measure Information:

Title

measurement of the sickle red cell response to epinephrine

Description

Time Frame

1-4 weeks

Secondary Outcome Measure Information:

Title

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

Description

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

Time Frame

within 24 hours after drug administration

10. Eligibility

Sex

All

Minimum Age & Unit of Time

10 Years

Maximum Age & Unit of Time

17 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ofelia A Alvarez, MD

Organizational Affiliation

University of Miami

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Miami

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

Citations:

PubMed Identifier

20456345

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.

Results Reference

background

PubMed Identifier

18550886

Citation

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.

Results Reference

result

PubMed Identifier

19840322

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.

Results Reference

result

PubMed Identifier

20117846

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.

Results Reference

result

PubMed Identifier

20732454

Citation

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.

Results Reference

result

PubMed Identifier

20797926

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.

Results Reference

result

PubMed Identifier

20936416

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.

Results Reference

result

Citation

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

Results Reference

result

PubMed Identifier

20644039

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.

Results Reference

result

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

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