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

• Sponsor: Laura M. De Castro, MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT01077921
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 31
• Location: 1
• Arms: 2
• Duration (Months): 42
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Sickle Cell Disease	Drug: Propranolol; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• 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: Jun 1, 2010
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Propranolol Drug arm	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).
Placebo Comparator: Sugar pill Placebo arm	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).

Outcome Measures

Primary Outcome Measures

1. SS RBC Adhesion (Epi -1d/cm2- vs. Sham) by Treatment [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

2. SS RBC Adhesion (Epi -2d/cm2- vs. Sham) by Treatment [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

3. SS RBC Adhesion (Epi -3d/cm2- vs. Sham) by Treatment [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

Secondary Outcome Measures

1. Overall Change of Plasma Levels of sE-selectin [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).

2. Overall Change of Plasma Levels of sP-selectin [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).

3. Overall Change of Plasma Levels of sICAM-1 [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)

4. Overall Change of Plasma Levels of sVCAM-1 [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)

5. Overall Change of Hemoglobin (Hgb) Levels [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

6. Overall Change of Hematocrit (Hct) Levels [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

7. Overall Change of Lactate Dehydrogenase (LDH) Levels [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

8. Overall Change of Oxygen Saturation (02Sat) Levels [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

9. Overall Change of Systolic Blood Pressure Levels [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

10. Overall Change of Diastolic Blood Pressure Levels [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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke University Medical Center	Durham	North Carolina	United States	27710

Sponsors and Collaborators

• Laura M. De Castro, MD
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

• De Castro LM, Zennadi R, Jonassaint JC, Batchvarova M, Telen MJ. Effect of propranolol as antiadhesive therapy in sickle cell disease. Clin Transl Sci. 2012 Dec;5(6):437-44. doi: 10.1111/cts.12005. Epub 2012 Oct 17.
• Eyler CE, Jackson T, Elliott LE, De Castro LM, Jonassaint J, Ashley-Koch A, Telen MJ. beta(2)-Adrenergic receptor and adenylate cyclase gene polymorphisms affect sickle red cell adhesion. Br J Haematol. 2008 Apr;141(1):105-8. doi: 10.1111/j.1365-2141.2008.07008.x.
• Zennadi R, Chien A, Xu K, Batchvarova M, Telen MJ. Sickle red cells induce adhesion of lymphocytes and monocytes to endothelium. Blood. 2008 Oct 15;112(8):3474-83. doi: 10.1182/blood-2008-01-134346. Epub 2008 Jul 29.
• Zennadi R, Hines PC, De Castro LM, Cartron JP, Parise LV, Telen MJ. Epinephrine acts through erythroid signaling pathways to activate sickle cell adhesion to endothelium via LW-alphavbeta3 interactions. Blood. 2004 Dec 1;104(12):3774-81. Epub 2004 Aug 12.
• Zennadi R, Moeller BJ, Whalen EJ, Batchvarova M, Xu K, Shan S, Delahunty M, Dewhirst MW, Telen MJ. Epinephrine-induced activation of LW-mediated sickle cell adhesion and vaso-occlusion in vivo. Blood. 2007 Oct 1;110(7):2708-17. Epub 2007 Jul 3.

• Responsible Party: Laura M. De Castro, MD, Associate Professor, Duke University
• ClinicalTrials.gov Identifier: NCT01077921
• Other Study ID Numbers: Pro00018427; K01HL096434-02; 5R21HL096123-02
• First Posted: Mar 1, 2010
• Last Update Posted: Jan 22, 2015
• Last Verified: Jan 1, 2015

• Keywords provided by Laura M. De Castro, MD, Associate Professor, Duke University: sickle; adhesion; propranolol
• Additional relevant MeSH terms: Anemia, Sickle Cell; Propranolol

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from the Duke adult sickle cell clinic. Those that consented underwent a screening visit to determine eligibility. If eligible they were enrolled on the study and received study drug within 30 days of screening
Pre-assignment Detail	Eighty-four patients were approached for the study, of those 28 declined to participate, 14 remained undecided. Forty-two patients consented. Thirthy-one of those consenting were enrolled and 27 randomized to the study.

Arm/Group Title	Propranolol-first	Placebo-first
Arm/Group Description	Cross-over study comprising treatment with propranolol for 6 weeks with a standard dose of 40 mg every 12 hrs, followed by a 2 weeks period washout, then similar treatment period with placebo followed by another 2 weeks washout period	Cross-over study comprising treatment with placebo for 6 weeks, followed by a 2 weeks period washout, then similar treatment period with propranolol with a standard dose of 40 mg every 12 hrs., followed by another 2 weeks washout period.
Period Title: First Intervention
STARTED	14	13
COMPLETED	13	12
NOT COMPLETED	1	1
Period Title: First Intervention
STARTED	13	12
COMPLETED	13	10
NOT COMPLETED	0	2
Period Title: First Intervention
STARTED	13	10
COMPLETED	13	9
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Propranolol-first	Placebo-first	Total
Arm/Group Description	Cross-over study comprising treatment with propranolol for 6 weeks with a standard dose of 40 mg every 12 hrs, followed by a 2 weeks period washout, then similar treatment period with placebo followed by another 2 weeks washout period	Cross-over study comprising treatment with placebo for 6 weeks, followed by a 2 weeks period washout, then similar treatment period with propranolol with a standard dose of 40 mg every 12 hrs., followed by another 2 weeks washout period	Total of all reporting groups
Overall Participants	14	13	27
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	34.2	26.1	30.4
Sex: Female, Male (Count of Participants)
Female	8 57.1%	9 69.2%	17 63%
Male	6 42.9%	4 30.8%	10 37%
Region of Enrollment (participants) [Number]
United States	14 100%	13 100%	27 100%

Outcome Measures

1. Primary Outcome

Title	SS RBC Adhesion (Epi -1d/cm2- vs. Sham) by Treatment
Description	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
Time Frame	Week 0 to 6 and week 8 to 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Propranolol	Placebo
Arm/Group Description	All subjects completing the propranolol treatment phase.	All subjects completing the placebo treatment phase.
Measure Participants	22	23
Epinephrine Treated Red blood cells	0 (24.4)	-0.3 (20.1)
unstimulated cells (Sham treated)	7.4 (18.7)	2.7 (26)

2. Secondary Outcome

Title	Overall Change of Plasma Levels of sE-selectin
Description	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).
Time Frame	Week 0 to 6 and week 8 to 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Propranolol	Placebo
Arm/Group Description	All subjects completing the propranolol treatment phase.	All subjects completing placebo treatment phase.
Measure Participants	22	23
Mean (Standard Deviation) [ng/ml]	-3.9 (12.1)	3.7 (9.3)

3. Primary Outcome

Title	SS RBC Adhesion (Epi -2d/cm2- vs. Sham) by Treatment
Description	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
Time Frame	Week 0 to 6 and week 8 to 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Propranolol	Placebo
Arm/Group Description	All subjects completing the propranolol treatment phase.	All subjects completing placebo treatment phase.
Measure Participants	22	23
Epi-treated Red blood cells	0.2 (13.8)	-2.8 (10.7)
unstimulated cells (Sham treated)	2.7 (11.2)	4.4 (13)

4. Primary Outcome

Title	SS RBC Adhesion (Epi -3d/cm2- vs. Sham) by Treatment
Description	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
Time Frame	Week 0 to 6 and week 8 to 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Propranolol	Placebo
Arm/Group Description	All subjects completing the propranolol treatment phase.	All subjects completing placebo treatment phase.
Measure Participants	22	23
Epi-treated Red blood cells	0.5 (9.7)	-2.8 (7.5)
unstimulated cells (Sham treated)	-0.1 (9.3)	4.3 (10)

5. Secondary Outcome

Title	Overall Change of Plasma Levels of sP-selectin
Description	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).
Time Frame	Week 0 to 6 and week 8 to 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Propranolol	Placebo
Arm/Group Description	All subjects completing the propranolol treatment phase.	All subjects completing placebo treatment phase.
Measure Participants	22	23
Mean (Standard Deviation) [ng/ml]	-5 (13.9)	-12.8 (54.8)

6. Secondary Outcome

Title	Overall Change of Plasma Levels of sICAM-1
Description	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)
Time Frame	Week 0 to 6 and week 8 to 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Propranolol	Placebo
Arm/Group Description	All subjects completing the propranolol treatment phase.	All subjects completing placebo treatment phase.
Measure Participants	22	23
Mean (Standard Deviation) [ng/ml]	-6.4 (15.3)	5.4 (28.5)

7. Secondary Outcome

Title	Overall Change of Plasma Levels of sVCAM-1
Description	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)
Time Frame	Week 0 to 6 and week 8 to 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Propranolol	Placebo
Arm/Group Description	All subjects completing the propranolol treatment phase.	All subjects completing placebo treatment phase.
Measure Participants	22	23
Mean (Standard Deviation) [ng/ml]	-16.7 (144.2)	-7.2 (117.7)

8. Secondary Outcome

Title	Overall Change of Hemoglobin (Hgb) Levels
Description	Overall change of Hemoglobin (Hgb) levels from baseline to post intervention( Week 0 to 6 and week 8 to 14) Placebo vs. Propranolol treated
Time Frame	Week 0 to 6 and week 8 to 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Propranolol	Placebo
Arm/Group Description	All subjects completing the propranolol treatment phase.	All subjects completing placebo treatment phase.
Measure Participants	22	23
Median (Inter-Quartile Range) [gm/dL]	0.2	-0.1

9. Secondary Outcome

Title	Overall Change of Hematocrit (Hct) Levels
Description	Overall change of Hematocrit (Hct) levels from baseline to post intervention( Week 0 to 6 and week 8 to 14) Placebo vs. Propranolol treated
Time Frame	Week 0 to 6 and week 8 to 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Propranolol	Placebo
Arm/Group Description	All subjects completing the propranolol treatment phase.	All subjects completing placebo treatment phase.
Measure Participants	22	23
Median (Inter-Quartile Range) [percentage of red blood cells]	1	0

10. Secondary Outcome

Title	Overall Change of Lactate Dehydrogenase (LDH) Levels
Description	Overall change of LDH levels from baseline to post intervention( Week 0 to 6 and week 8 to 14) Placebo vs. Propranolol treated
Time Frame	Week 0 to 6 and week 8 to 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Propranolol	Placebo
Arm/Group Description	All subjects completing the propranolol treatment phase.	All subjects completing placebo treatment phase.
Measure Participants	22	23
Median (Inter-Quartile Range) [IU/L]	24	-5

11. Secondary Outcome

Title	Overall Change of Oxygen Saturation (02Sat) Levels
Description	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
Time Frame	Week 0 to 6 and week 8 to 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Propranolol	Placebo
Arm/Group Description	All subjects completing the propranolol treatment phase.	All subjects completing placebo treatment phase.
Measure Participants	22	23
Median (Inter-Quartile Range) [percentage of oxygen saturation]	0	0

12. Secondary Outcome

Title	Overall Change of Systolic Blood Pressure Levels
Description	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
Time Frame	Week 0 to 6 and week 8 to 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Propranolol	Placebo
Arm/Group Description	All subjects completing the propranolol treatment phase.	All subjects completing placebo treatment phase.
Measure Participants	22	23
Median (Inter-Quartile Range) [mmHg]	-1.0	-1.0

13. Secondary Outcome

Title	Overall Change of Diastolic Blood Pressure Levels
Description	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
Time Frame	Week 0 to 6 and week 8 to 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Propranolol	Placebo
Arm/Group Description	All subjects completing the propranolol treatment phase.	All subjects completing placebo treatment phase.
Measure Participants	22	23
Median (Inter-Quartile Range) [mmHg]	0	-1

Adverse Events

Adverse Event Reporting Description	All patients who were enrolled and had at least one baseline visit are included in the "at risk" category.
Arm/Group Title	Propranolol		Placebo
Arm/Group Description	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).		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).
All Cause Mortality
	Propranolol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Propranolol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/27 (14.8%)		3/27 (11.1%)
Musculoskeletal and connective tissue disorders
Vaso-occlusive crisis resulting in hospitalization	4/27 (14.8%)		3/27 (11.1%)
Other (Not Including Serious) Adverse Events
	Propranolol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/27 (81.5%)		19/27 (70.4%)
Blood and lymphatic system disorders
Lymphadenopathy	0/27 (0%)		1/27 (3.7%)
Thrombocytopenia	1/27 (3.7%)		1/27 (3.7%)
Cardiac disorders
Atrioventricular (AV) block	0/27 (0%)		2/27 (7.4%)
Bradycardia	1/27 (3.7%)		0/27 (0%)
Drop in Blood Pressure	0/27 (0%)		1/27 (3.7%)
Eye disorders
Bilateral conjunctivitis	0/27 (0%)		1/27 (3.7%)
Gastrointestinal disorders
Abdominal Paiin	1/27 (3.7%)		2/27 (7.4%)
Abdominal cramping	1/27 (3.7%)		0/27 (0%)
Abdominal pain and bloating	1/27 (3.7%)		0/27 (0%)
Blood per rectum	1/27 (3.7%)		0/27 (0%)
Diarrhea	1/27 (3.7%)		2/27 (7.4%)
Diarrhea, intermittent	1/27 (3.7%)		0/27 (0%)
Nausea	1/27 (3.7%)		0/27 (0%)
Nausea and vomiting	1/27 (3.7%)		2/27 (7.4%)
Stomach ache	1/27 (3.7%)		1/27 (3.7%)
General disorders
Extreme tiredness	0/27 (0%)		2/27 (7.4%)
Fatigue	4/27 (14.8%)		4/27 (14.8%)
Feeling of internal heat	1/27 (3.7%)		0/27 (0%)
Increased Fatigue	1/27 (3.7%)		0/27 (0%)
Shakes	0/27 (0%)		1/27 (3.7%)
ED Visit	0/27 (0%)		3/27 (11.1%)
Infections and infestations
E Coli Bacteremia	0/27 (0%)		1/27 (3.7%)
Fever	1/27 (3.7%)		0/27 (0%)
MRSA Positive	1/27 (3.7%)		0/27 (0%)
Sinus Infection	1/27 (3.7%)		0/27 (0%)
Sore throat	0/27 (0%)		2/27 (7.4%)
Atypical mycoplasma pneumonia, Suspected	1/27 (3.7%)		0/27 (0%)
Metabolism and nutrition disorders
Sensitivity to cold	0/27 (0%)		1/27 (3.7%)
Musculoskeletal and connective tissue disorders
Pain Crisis	6/27 (22.2%)		4/27 (14.8%)
Pain, Back	0/27 (0%)		1/27 (3.7%)
Pain, Bone	0/27 (0%)		1/27 (3.7%)
Pain, Increased knee pain	0/27 (0%)		1/27 (3.7%)
Pain, Jaw	0/27 (0%)		1/27 (3.7%)
Pain, Joint	0/27 (0%)		1/27 (3.7%)
Pain, Knee	0/27 (0%)		1/27 (3.7%)
Pain, Left chest wall	0/27 (0%)		1/27 (3.7%)
Pain, Leg	1/27 (3.7%)		1/27 (3.7%)
Pain, Musculoskeletal	1/27 (3.7%)		4/27 (14.8%)
Pain, back and chest	0/27 (0%)		2/27 (7.4%)
Toothache	0/27 (0%)		1/27 (3.7%)
Vaso-occlusive Crisis	2/27 (7.4%)		2/27 (7.4%)
Fracture, left foot	1/27 (3.7%)		0/27 (0%)
Fatigue with chest tightness	1/27 (3.7%)		0/27 (0%)
Pain, Hip	1/27 (3.7%)		0/27 (0%)
Pain, Migrating	1/27 (3.7%)		0/27 (0%)
Pain episode	1/27 (3.7%)		0/27 (0%)
Pain, Right foot, plantar	1/27 (3.7%)		0/27 (0%)
Pain, Leg, sharp shooting	1/27 (3.7%)		0/27 (0%)
Pain, Shoulder/Chest	1/27 (3.7%)		0/27 (0%)
Weakness	1/27 (3.7%)		0/27 (0%)
Nervous system disorders
Dizziness	1/27 (3.7%)		5/27 (18.5%)
Headache	8/27 (29.6%)		8/27 (29.6%)
Headache, extreme	0/27 (0%)		1/27 (3.7%)
Dizziness/Vertigo	1/27 (3.7%)		0/27 (0%)
Headache, Intermittent	1/27 (3.7%)		0/27 (0%)
Lightheadness	1/27 (3.7%)		0/27 (0%)
Vertigo	1/27 (3.7%)		0/27 (0%)
Psychiatric disorders
Worsening depression	0/27 (0%)		1/27 (3.7%)
Renal and urinary disorders
Pylonephritis due to E. Coli	0/27 (0%)		1/27 (3.7%)
Smelly urine and bladder spasms	0/27 (0%)		1/27 (3.7%)
Reproductive system and breast disorders
Delayed menstrual period	0/27 (0%)		1/27 (3.7%)
Prolonged menstrual period	0/27 (0%)		1/27 (3.7%)
Respiratory, thoracic and mediastinal disorders
Congestion, Upper Chest	0/27 (0%)		1/27 (3.7%)
Cough	6/27 (22.2%)		1/27 (3.7%)
Coughing, congestion	0/27 (0%)		1/27 (3.7%)
Hoarseness	0/27 (0%)		1/27 (3.7%)
Nasal Congestion	1/27 (3.7%)		4/27 (14.8%)
Sneezing/Allergies	0/27 (0%)		1/27 (3.7%)
Thrush	1/27 (3.7%)		0/27 (0%)
Cold symptoms	2/27 (7.4%)		0/27 (0%)
Shortness of breath on exertion	1/27 (3.7%)		0/27 (0%)
Sore throat, intermittent	1/27 (3.7%)		0/27 (0%)
Runny nose	1/27 (3.7%)		0/27 (0%)
Shortness of breath	1/27 (3.7%)		0/27 (0%)
sinus allergies	2/27 (7.4%)		0/27 (0%)
Congestion, Sinus	1/27 (3.7%)		0/27 (0%)
Sore throat, worsening	1/27 (3.7%)		0/27 (0%)
Skin and subcutaneous tissue disorders
Rash	0/27 (0%)		1/27 (3.7%)
Skin abrasions due to pruritus	0/27 (0%)		1/27 (3.7%)
Skin abrasions due to pruritis	1/27 (3.7%)		0/27 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.