Study of Propranolol as Anti-Adhesive Therapy in Sickle Cell Disease (SCD)
Condition: Sickle Cell Disease
MeSH terms: Anemia, Sickle Cell
Intervention: Propranolol; Placebo
Intervention description: Treatment will be with a standard propranolol dose of 40 mg every 12 hrs.Each patient will participate in 6 weeks of treatment with placebo or study drug (propranolol), followed by a 2-week wash-out period and then 6 weeks of treatment with the other modality (placebo or propranolol).; Treatment will be with a standard propranolol dose of 40 mg every 12 hrs.Each patient will participate in 6 weeks of treatment with placebo or study drug (propranolol), followed by a 2-week wash-out period and then 6 weeks of treatment with the other modality (placebo or propranolol).
Intervention MeSH terms: Propranolol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: sickle; adhesion; propranolol

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.
    

Eligibility 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