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

Laura M. De Castro, MD

Status and phase

Completed

Phase 2

Conditions

Sickle Cell Disease

Treatments

Drug: Placebo

Drug: Propranolol

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT01077921

5R21HL096123-02 (U.S. NIH Grant/Contract)

Pro00018427

K01HL096434-02 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Enrollment

31 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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