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

Phase 1

Terminated

• Conditions: Sickle Cell Disease
• Interventions: Drug: propranolol

• Registration Number: NCT02012777
• Lead Sponsor: University of Miami

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.

Study Timeline

• Study Start: 2010-06
• Primary Completion: 2012-11
• Study Completion: 2013-04-03
• Study First Submitted: 2013-12-06
• Study First Submitted QC: 2013-12-10
• Study First Posted: 2013-12-16
• Status Verified: 2017-06
• Last Update Submitted: 2017-06-06
• Last Update Posted: 2017-06-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 9

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
cohort 1 10mg propranolol	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.
cohort 2 20mg propranolol	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.
cohort 3 40mg propranolol	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.

Primary Outcome Measures

Name	Time	Method
measurement of the sickle red cell response to epinephrine	1-4 weeks	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

Name	Time	Method
Safety data regarding the use of propanolol in children with sickle cell disease	within 24 hours after drug administration	1. New onset wheezing; 2. Onset of low blood pressure defined as blood pressure less than 90/50; 3. Onset of heart rate less than 60 beats/min

Trial Locations

Locations (1)

University of Miami; 🇺🇸 Miami, Florida, United States