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

• Status: Completed
• Trial end date: 2013-12-01
• Target enrollment: 0
• Participant gender: All

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 Sickle Red Blood Cell (SS RBC) adhesion by epinephrine.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Laura M. De Castro, MD
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Propranolol

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 Thyroid Stimulating Hormone (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, myocardial infarct (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