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Study of Propranolol as Anti-Adhesive Therapy in Sickle Cell Disease (SCD)

Information source: Duke University
Information obtained from ClinicalTrials.gov on February 07, 2013
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Sickle Cell Disease

Intervention: Propranolol (Drug); Placebo (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Duke University

Overall contact:
Laura M De Castro, MD, Phone: (919)684-6464, Email: decas004@mc.duke.edu

Summary

An open label, prospective, randomized cross-over phase II study in up to 60 sickle cell patients who are either homozygous for Hb S or have HbSB0 thalassemia. Initially, each patient will be treated for 6 weeks with placebo or a standard dose of propranolol (40 mg) every 12 hrs. This will be followed by a 2-week washout period after which, patients will receive the other treatment modality (placebo or propranolol).

We Hypothesize that propranolol administered in vivo on a daily basis for 6 weeks (1) will decrease baseline adhesion to endothelial cells and will substantially abrogate epinephrine-stimulated adhesion to endothelial cells, as measured in vitro; (2) will improve biomarkers of endothelial activation and dysfunction; and (3) can be safely used in patients with SCD. Thus, the use of propranolol in SCD may represent a safe and effective means of anti-adhesive therapy in SCD.

Study Objectives:

Primary Objective:

• To establish the safety and efficacy of long-term therapy with propranolol as an anti-adhesive therapy for SCD.

Secondary Objective:

• To evaluate changes in soluble markers of endothelial activation and dysfunction.

Correlative Science Objective:

• To determine whether response to propranolol therapy is associated with polymorphisms in genes encoding the proteins involved in the upregulation of SS RBC adhesion by epinephrine.

Clinical Details

Official title: Phase II Study of Propranolol as Anti-Adhesive Therapy for Sickle Cell Disease

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Establish the safety and efficacy of long-term therapy with propranolol as an anti-adhesive therapy for SCD

Secondary outcome: Evaluate changes in soluble markers of endothelial activation and dysfunction.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Diagnosis by electrophoresis (HEP) of Hemoglobin (Hgb) SS or Hgb Sβ0 thalassemia (all

patients followed at our clinic have HEP-confirmed diagnosis on file)

- Age ≥ 18 years

- Blood pressure (BP) Systolic ≥ 95mm Hg and Diastolic ≥ 50mm Hg

- Heart rate (HR) ≥ 70 and ≤ 110 bpm

- Oxygen saturation by pulse oximeter and at room air ≥ 92%

- Hematocrit (Hct) ≥ 20% and Hb > 6. 0 g/dL

- Euthyroid status as indicated by normal TSH

- SS RBCs obtained during screening period demonstrating an adhesion response to

epinephrine of 40% over non-stimulated baseline adhesion to endothelial cells

- Capacity to understand and sign informed consent

Exclusion Criteria:

- History of vaso-occlusive episode during the 6 wks prior to screening

- RBC transfusion during the 3 months prior to study entry

- Ongoing pregnancy

- History of heart failure, MI, bradyarrhythmias, conduction defects

- History of asthma or reactive airway disease

- History of thyroid disease

- Diabetes

- Renal insufficiency (BUN >21 mg/dL and/or Creatinine >1. 4 mg/dL)

- Use during the screening or study period of any of the following medications:

antihypertensives, diuretics, thyroid replacement therapy, anti-arrhythmia medications, bronchodilators, inhaled steroids, insulin, or hypoglycemic medication

- History of allergy to sulfonamides

Locations and Contacts

Laura M De Castro, MD, Phone: (919)684-6464, Email: decas004@mc.duke.edu

Duke University Medical Center, Durham, North Carolina 27710, United States; Recruiting
Laura M De Castro, MD, Principal Investigator
Marilyn J Telen, MD, Sub-Investigator
Allison Ashley-Koch, PhD, Sub-Investigator
Additional Information

Related publications:

Zennadi R, Hines PC, De Castro LM, Cartron JP, Parise LV, Telen MJ. Epinephrine acts through erythroid signaling pathways to activate sickle cell adhesion to endothelium via LW-alphavbeta3 interactions. Blood. 2004 Dec 1;104(12):3774-81. Epub 2004 Aug 12.

Zennadi R, Moeller BJ, Whalen EJ, Batchvarova M, Xu K, Shan S, Delahunty M, Dewhirst MW, Telen MJ. Epinephrine-induced activation of LW-mediated sickle cell adhesion and vaso-occlusion in vivo. Blood. 2007 Oct 1;110(7):2708-17. Epub 2007 Jul 3.

Zennadi R, Chien A, Xu K, Batchvarova M, Telen MJ. Sickle red cells induce adhesion of lymphocytes and monocytes to endothelium. Blood. 2008 Oct 15;112(8):3474-83. Epub 2008 Jul 29.

Eyler CE, Jackson T, Elliott LE, De Castro LM, Jonassaint J, Ashley-Koch A, Telen MJ. beta(2)-Adrenergic receptor and adenylate cyclase gene polymorphisms affect sickle red cell adhesion. Br J Haematol. 2008 Apr;141(1):105-8.

Starting date: June 2010
Last updated: October 7, 2010

Page last updated: February 07, 2013

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