Study of Propranolol as Anti-Adhesive Therapy in Sickle Cell Disease (SCD)
| Status: | Completed |
|---|---|
| Conditions: | Anemia |
| Therapuetic Areas: | Hematology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 3/30/2013 |
| Start Date: | June 2010 |
| End Date: | July 2012 |
| Contact: | Laura M De Castro, MD |
| Email: | decas004@mc.duke.edu |
| Phone: | (919)684-6464 |
Phase II Study of Propranolol as Anti-Adhesive Therapy for Sickle Cell Disease
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.
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
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