Study of Propranolol as Anti-Adhesive Therapy in Sickle Cell Disease (SCD)
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ClinicalTrials.gov Identifier: NCT01077921 |
Recruitment Status
:
Completed
First Posted
: March 1, 2010
Results First Posted
: January 22, 2015
Last Update Posted
: January 22, 2015
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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.
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Sickle Cell Disease | Drug: Propranolol Drug: Placebo | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 31 participants |
Allocation: | Randomized |
Intervention Model: | Crossover Assignment |
Masking: | Triple (Participant, Care Provider, Investigator) |
Primary Purpose: | Treatment |
Official Title: | Phase II Study of Propranolol as Anti-Adhesive Therapy for Sickle Cell Disease |
Study Start Date : | June 2010 |
Actual Primary Completion Date : | December 2013 |
Actual Study Completion Date : | December 2013 |

Arm | Intervention/treatment |
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Experimental: Propranolol
Drug arm
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Drug: 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).
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Placebo Comparator: Sugar pill
Placebo arm
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Drug: Placebo
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).
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- SS RBC Adhesion (Epi -1d/cm2- vs. Sham) by Treatment [ Time Frame: 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 -2d/cm2- vs. Sham) by Treatment [ Time Frame: 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
- SS RBC Adhesion (Epi -3d/cm2- vs. Sham) by Treatment [ Time Frame: 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
- Overall Change of Plasma Levels of sE-selectin [ Time Frame: Week 0 to 6 and week 8 to 14 ]Biomarkers of Endothelial Activation and Dysfunction: Overall change of Plasma levels of sE-selectin measured in triplicate on plasma samples using commercially available ELISA kits from baseline to post intervention ( Week 0 to 6 and week 8 to 14).
- Overall Change of Plasma Levels of sP-selectin [ Time Frame: Week 0 to 6 and week 8 to 14 ]Biomarkers of Endothelial Activation and Dysfunction: Overall change of Plasma levels of sP-selectin measured in triplicate on plasma samples using commercially available ELISA kits from baseline to post intervention ( Week 0 to 6 and weeks 8 to 14).
- Overall Change of Plasma Levels of sICAM-1 [ Time Frame: Week 0 to 6 and week 8 to 14 ]Biomarkers of Endothelial Activation and Dysfunction: Overall change of Plasma levels of sICAM-1 measured in triplicate on plasma samples using commercially available ELISA kits from baseline to post intervention ( Week 0 to 6 and week 8 to 14)
- Overall Change of Plasma Levels of sVCAM-1 [ Time Frame: Week 0 to 6 and week 8 to 14 ]Biomarkers of Endothelial Activation and Dysfunction: Overall change of Plasma levels of sVCAM-1 measured in triplicate on plasma samples using commercially available ELISA kits from baseline to post intervention ( Week 0 to 6 or week 8 to 14)
- Overall Change of Hemoglobin (Hgb) Levels [ Time Frame: Week 0 to 6 and week 8 to 14 ]Overall change of Hemoglobin (Hgb) levels from baseline to post intervention( Week 0 to 6 and week 8 to 14) Placebo vs. Propranolol treated
- Overall Change of Hematocrit (Hct) Levels [ Time Frame: Week 0 to 6 and week 8 to 14 ]Overall change of Hematocrit (Hct) levels from baseline to post intervention( Week 0 to 6 and week 8 to 14) Placebo vs. Propranolol treated
- Overall Change of Lactate Dehydrogenase (LDH) Levels [ Time Frame: Week 0 to 6 and week 8 to 14 ]Overall change of LDH levels from baseline to post intervention( Week 0 to 6 and week 8 to 14) Placebo vs. Propranolol treated
- Overall Change of Oxygen Saturation (02Sat) Levels [ Time Frame: Week 0 to 6 and week 8 to 14 ]Overall change of Oxygen Saturation (02Sat) levels from baseline to post intervention( Week 0 to 6 and week 8 to 14) Placebo vs. Propranolol treated
- Overall Change of Systolic Blood Pressure Levels [ Time Frame: Week 0 to 6 and week 8 to 14 ]Overall change of Systolic Blood Pressure levels from baseline to post intervention (Week 0 to 6 and week 8 to 14) Placebo vs. Propranolol treated
- Overall Change of Diastolic Blood Pressure Levels [ Time Frame: Week 0 to 6 and week 8 to 14 ]Overall change of Diastolic Blood Pressure levels from baseline to post intervention (Week 0 to 6 and week 8 to 14) Placebo vs. Propranolol treated

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Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01077921
United States, North Carolina | |
Duke University Medical Center | |
Durham, North Carolina, United States, 27710 |
Publications:
Responsible Party: | Laura M. De Castro, MD, Associate Professor, Duke University Medical Center |
ClinicalTrials.gov Identifier: | NCT01077921 History of Changes |
Other Study ID Numbers: |
Pro00018427 K01HL096434-02 ( U.S. NIH Grant/Contract ) 5R21HL096123-02 ( U.S. NIH Grant/Contract ) |
First Posted: | March 1, 2010 Key Record Dates |
Results First Posted: | January 22, 2015 |
Last Update Posted: | January 22, 2015 |
Last Verified: | January 2015 |
Keywords provided by Laura M. De Castro, MD, Duke University Medical Center:
sickle adhesion propranolol |
Additional relevant MeSH terms:
Anemia, Sickle Cell Anemia, Hemolytic, Congenital Anemia, Hemolytic Anemia Hematologic Diseases Hemoglobinopathies Genetic Diseases, Inborn Propranolol Adrenergic beta-Antagonists |
Adrenergic Antagonists Adrenergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Anti-Arrhythmia Agents Antihypertensive Agents Vasodilator Agents |