Phase II Study of Propranolol as Anti-Adhesive Therapy for Sickle Cell Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- SS RBC Adhesion (Epi -1d/cm2- vs. Sham) by Treatment
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •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
研究组 & 干预措施
Propranolol
Drug arm
干预措施: Propranolol (Drug)
Sugar pill
Placebo arm
干预措施: Placebo (Drug)
结局指标
主要结局
SS RBC Adhesion (Epi -1d/cm2- vs. Sham) by Treatment
时间窗: Week 0 to 6 and week 8 to 14
The stickiness of SS RBC will be evaluated by a well-established in vitro assay of adhesion of SS RBCs to cultured endothelial cells using a flow chamber. Overall change of adhesion from baseline to post intervention( Week 0 to 6 and week 8 to 14) in unstimulated cells (Sham treated) vs. Stimulated Red Blood Cells (Epi-treated) at 1 dyne/cm2
SS RBC Adhesion (Epi -3d/cm2- vs. Sham) by Treatment
时间窗: Week 0 to 6 and week 8 to 14
The stickiness of SS RBC will be evaluated by a well-established in vitro assay of adhesion of SS RBCs to cultured endothelial cells using a flow chamber. Overall change of adhesion from baseline to post intervention( Week 0 to 6 and week 8 to 14) in unstimulated cells (Sham treated) vs. Stimulated Red Blood Cells (Epi-treated) at 3 dyne/cm2
SS RBC Adhesion (Epi -2d/cm2- vs. Sham) by Treatment
时间窗: Week 0 to 6 and week 8 to 14
The stickiness of SS RBC will be evaluated by a well-established in vitro assay of adhesion of SS RBCs to cultured endothelial cells using a flow chamber. Overall change of adhesion from baseline to post intervention( Week 0 to 6 and week 8 to 14) in unstimulated cells (Sham treated) vs. Stimulated Red Blood Cells (Epi-treated) at 2 dyne/cm2
次要结局
- Overall Change of Plasma Levels of sVCAM-1(Week 0 to 6 and week 8 to 14)
- Overall Change of Plasma Levels of sE-selectin(Week 0 to 6 and week 8 to 14)
- Overall Change of Plasma Levels of sP-selectin(Week 0 to 6 and week 8 to 14)
- Overall Change of Plasma Levels of sICAM-1(Week 0 to 6 and week 8 to 14)
- Overall Change of Hemoglobin (Hgb) Levels(Week 0 to 6 and week 8 to 14)
- Overall Change of Lactate Dehydrogenase (LDH) Levels(Week 0 to 6 and week 8 to 14)
- Overall Change of Hematocrit (Hct) Levels(Week 0 to 6 and week 8 to 14)
- Overall Change of Oxygen Saturation (02Sat) Levels(Week 0 to 6 and week 8 to 14)
- Overall Change of Systolic Blood Pressure Levels(Week 0 to 6 and week 8 to 14)
- Overall Change of Diastolic Blood Pressure Levels(Week 0 to 6 and week 8 to 14)
研究者
Laura M. De Castro, MD
Associate Professor
Duke University