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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by University of Miami
Sponsor:
Collaborator:
Duke University
Information provided by (Responsible Party):
Ofelia Alvarez, University of Miami
ClinicalTrials.gov Identifier:
NCT02012777
First received: December 6, 2013
Last updated: November 5, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention Phase
Sickle Cell Disease
Drug: propranolol
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Propanolol Effect on Red Cell Adhesion in Non-Asthmatic Children With Sickle Cell Disease: A Dose Finding Study

Resource links provided by NLM:


Further study details as provided by University of Miami:

Primary Outcome Measures:
  • measurement of the sickle red cell response to epinephrine [ Time Frame: 1-4 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: within 24 hours after drug administration ] [ Designated as safety issue: Yes ]
    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


Estimated Enrollment: 20
Study Start Date: June 2010
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.

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.
Other Names:
  • propanolol systemic
  • Inderal
  • Inderal LA
  • InnoPran XL
Active Comparator: 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.
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.
Other Names:
  • propanolol systemic
  • Inderal
  • Inderal LA
  • InnoPran XL
Active Comparator: 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.
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.
Other Names:
  • propanolol systemic
  • Inderal
  • Inderal LA
  • InnoPran XL

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.

  Eligibility

Ages Eligible for Study:   7 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. diagnosis of HbSS or HbSBeta0Thal
  2. age 7-17 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02012777

Contacts
Contact: Ofelia Alvarez, MD 305.243.0846 oalvarez2@med.miami.edu
Contact: Tally Hustace, ARNP 305.243.6924 thustace@med.miami.edu

Locations
United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33136
Contact: Ofelia Alvarez, MD    305-243-0846    oalvarez2@med.miami.edu   
Contact: Tally Hustace, ARNP    305.243.6924    thustace@med.miami.edu   
Principal Investigator: Ofelia Alvarez, MD         
Sponsors and Collaborators
University of Miami
Duke University
Investigators
Principal Investigator: Ofelia A Alvarez, MD University of Miami
  More Information

Publications:

Responsible Party: Ofelia Alvarez, Professor of Clinical Pediatrics, University of Miami
ClinicalTrials.gov Identifier: NCT02012777     History of Changes
Other Study ID Numbers: 20100334
Study First Received: December 6, 2013
Last Updated: November 5, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Miami:
sickle cell disease
propanolol
red blood cell adhesion

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia
Anemia, Hemolytic
Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn
Hematologic Diseases
Hemoglobinopathies
Propranolol
Adrenergic Agents
Adrenergic Antagonists
Adrenergic beta-Antagonists
Anti-Arrhythmia Agents
Antihypertensive Agents
Cardiovascular Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on November 27, 2014