Trial Outcomes & Findings for Effect of Atorvastatin on Endothelial Dysfunction and Albuminuria in Sickle Cell Disease (NCT NCT01732718)
NCT ID: NCT01732718
Last Updated: 2020-03-18
Results Overview
Endothelial function will be assessed using ultrasound imaging of the brachial artery, with measurement of endothelium-dependent (flow-mediated) and endothelium-independent (nitroglycerin-mediated) dilation of the artery measured in millimeters (mm).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
13 participants
Primary outcome timeframe
Baseline, 6 weeks
Results posted on
2020-03-18
Participant Flow
Participant milestones
| Measure |
Atorvastatin, Then Placebo
Participants first received Atorvastatin 40 mg tablets once daily for 6 weeks. After a washout period of 4 weeks, they then received placebo (matching Atorvastatin 40 mg tablets) once daily for 6 weeks.
Atorvastatin: 40 mg tablet by mouth daily for 6 weeks
Placebo: Matching placebo tablet by mouth daily for 6 weeks
|
Placebo, Then Atorvastatin
Participants first received Placebo (matching Atorvastatin 40 mg tablets) once daily for 6 weeks. After a washout period of 4 weeks, they then received Atorvastatin 40 mg tablets once daily for 6 weeks.
Atorvastatin: 40 mg tablet by mouth daily for 6 weeks
Placebo: Matching placebo tablet by mouth daily for 6 weeks
|
|---|---|---|
|
First Intervention
STARTED
|
7
|
6
|
|
First Intervention
COMPLETED
|
7
|
6
|
|
First Intervention
NOT COMPLETED
|
0
|
0
|
|
Washout (4 Weeks)
STARTED
|
7
|
6
|
|
Washout (4 Weeks)
COMPLETED
|
7
|
6
|
|
Washout (4 Weeks)
NOT COMPLETED
|
0
|
0
|
|
Second Intervention
STARTED
|
7
|
6
|
|
Second Intervention
COMPLETED
|
7
|
6
|
|
Second Intervention
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Effect of Atorvastatin on Endothelial Dysfunction and Albuminuria in Sickle Cell Disease
Baseline characteristics by cohort
| Measure |
All Study Participants
n=13 Participants
Participants who were randomized to receive either Atorvastatin 40 mg or Placebo (matching Atorvastatin 40 mg)
|
|---|---|
|
Age, Continuous
|
48 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
13 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
13 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, 6 weeksEndothelial function will be assessed using ultrasound imaging of the brachial artery, with measurement of endothelium-dependent (flow-mediated) and endothelium-independent (nitroglycerin-mediated) dilation of the artery measured in millimeters (mm).
Outcome measures
| Measure |
Atorvastatin
n=13 Participants
Participants who received Atorvastatin 40 mg tablet in either the first or the second intervention
|
Placebo
n=13 Participants
Participants who received placebo tablet (matching Atorvastatin 40 mg) in either the first or the second intervention
|
Week 6-Atorvastatin
Participants receiving Atorvastatin 40 mg tablets once daily for 6 weeks
|
Baseline-Placebo
Participants receiving Placebo once daily for 6 weeks
|
Week 4-Placebo
Participants receiving Placebo once daily for 6 weeks
|
Week 6-Placebo
Participants receiving Placebo once daily for 6 weeks
|
|---|---|---|---|---|---|---|
|
Change From Baseline to Week 6 in Endothelial Function
|
1.44 % diameter change
Interval -2.66 to 4.43
|
0.69 % diameter change
Interval -1.94 to 3.18
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, 6 weeksPopulation: Investigators elected to look at only one marker of vascular endothelial injury, i.e. sVCAM, so there is no data for sICAM.
Investigators will measure plasma levels of soluble vascular cell adhesion molecules (sVCAM) and soluble intracellular adhesion molecule (sICAM) at baseline and at 6 weeks of treatment.
Outcome measures
| Measure |
Atorvastatin
n=13 Participants
Participants who received Atorvastatin 40 mg tablet in either the first or the second intervention
|
Placebo
n=13 Participants
Participants who received placebo tablet (matching Atorvastatin 40 mg) in either the first or the second intervention
|
Week 6-Atorvastatin
Participants receiving Atorvastatin 40 mg tablets once daily for 6 weeks
|
Baseline-Placebo
Participants receiving Placebo once daily for 6 weeks
|
Week 4-Placebo
Participants receiving Placebo once daily for 6 weeks
|
Week 6-Placebo
Participants receiving Placebo once daily for 6 weeks
|
|---|---|---|---|---|---|---|
|
Change From Baseline to Week 6 in Plasma Markers of Endothelial Activation
|
22.99 ng/mL
Interval -58.8 to 41.7
|
7.54 ng/mL
Interval -75.2 to 149.9
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, 6 weeksPopulation: Data not collected
The expression and activity of heme oxygenase-1(HO-1)will be determined at baseline and at 6 weeks of treatment.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, 6 weeksInvestigators will measure plasma levels of soluble fms-like tyrosine kinase-1 (sFLT-1) at baseline and at 6 weeks of treatment.
Outcome measures
| Measure |
Atorvastatin
n=13 Participants
Participants who received Atorvastatin 40 mg tablet in either the first or the second intervention
|
Placebo
n=13 Participants
Participants who received placebo tablet (matching Atorvastatin 40 mg) in either the first or the second intervention
|
Week 6-Atorvastatin
Participants receiving Atorvastatin 40 mg tablets once daily for 6 weeks
|
Baseline-Placebo
Participants receiving Placebo once daily for 6 weeks
|
Week 4-Placebo
Participants receiving Placebo once daily for 6 weeks
|
Week 6-Placebo
Participants receiving Placebo once daily for 6 weeks
|
|---|---|---|---|---|---|---|
|
Change From Baseline to Week 6 in Plasma Levels of Soluble Fms-like Tyrosine Kinase-1 (sFLT-1)
|
19.2 pg/mL
Interval -47.1 to 47.7
|
36.9 pg/mL
Interval -20.9 to 129.6
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, 6 weeksPopulation: The stored samples did not survive the freeze/thaw process and as such, this data was not attainable.
Flow cytometry performed to assess monocyte activation at baseline and at 6 weeks of treatment.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, 6 weeksInvestigators will assess the effect of atorvastatin on albuminuria by spot urine microalbuminuria/creatinine ratio measured at baseline and at 6 weeks of treatment.
Outcome measures
| Measure |
Atorvastatin
n=13 Participants
Participants who received Atorvastatin 40 mg tablet in either the first or the second intervention
|
Placebo
n=13 Participants
Participants who received placebo tablet (matching Atorvastatin 40 mg) in either the first or the second intervention
|
Week 6-Atorvastatin
Participants receiving Atorvastatin 40 mg tablets once daily for 6 weeks
|
Baseline-Placebo
Participants receiving Placebo once daily for 6 weeks
|
Week 4-Placebo
Participants receiving Placebo once daily for 6 weeks
|
Week 6-Placebo
Participants receiving Placebo once daily for 6 weeks
|
|---|---|---|---|---|---|---|
|
Change From Baseline to Week 6 in Renal Function
|
28.8 ug per mg
Interval -28.6 to 237.1
|
74.9 ug per mg
Interval -15.2 to 373.4
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Continuously from randomization through end of studySubjects will be evaluated for safety by patient self-report of adverse events and results of laboratory tests.
Outcome measures
| Measure |
Atorvastatin
n=13 Participants
Participants who received Atorvastatin 40 mg tablet in either the first or the second intervention
|
Placebo
n=13 Participants
Participants who received placebo tablet (matching Atorvastatin 40 mg) in either the first or the second intervention
|
Week 6-Atorvastatin
Participants receiving Atorvastatin 40 mg tablets once daily for 6 weeks
|
Baseline-Placebo
Participants receiving Placebo once daily for 6 weeks
|
Week 4-Placebo
Participants receiving Placebo once daily for 6 weeks
|
Week 6-Placebo
Participants receiving Placebo once daily for 6 weeks
|
|---|---|---|---|---|---|---|
|
Occurrence of Adverse Events.
|
9 events
|
13 events
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, 2, 4, and 6 weeks during treatment, and at follow-up.Subjects will be evaluated by physical examination and/or measurement of vital signs at each study visit.
Outcome measures
| Measure |
Atorvastatin
n=13 Participants
Participants who received Atorvastatin 40 mg tablet in either the first or the second intervention
|
Placebo
n=13 Participants
Participants who received placebo tablet (matching Atorvastatin 40 mg) in either the first or the second intervention
|
Week 6-Atorvastatin
n=13 Participants
Participants receiving Atorvastatin 40 mg tablets once daily for 6 weeks
|
Baseline-Placebo
n=13 Participants
Participants receiving Placebo once daily for 6 weeks
|
Week 4-Placebo
n=13 Participants
Participants receiving Placebo once daily for 6 weeks
|
Week 6-Placebo
n=13 Participants
Participants receiving Placebo once daily for 6 weeks
|
|---|---|---|---|---|---|---|
|
Abnormal Physical Findings.
|
0 participants
|
2 participants
|
1 participants
|
1 participants
|
0 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Baseline, 6 weeksPopulation: Due to loss of key study personnel these data were not collected
The expression and activity of rho/rho kinase will be determined at baseline and at 6 weeks of treatment.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, 6 weeksInvestigators will measure plasma levels of vascular endothelial growth factor (VEGF) at baseline and at 6 weeks of treatment.
Outcome measures
| Measure |
Atorvastatin
n=13 Participants
Participants who received Atorvastatin 40 mg tablet in either the first or the second intervention
|
Placebo
n=13 Participants
Participants who received placebo tablet (matching Atorvastatin 40 mg) in either the first or the second intervention
|
Week 6-Atorvastatin
Participants receiving Atorvastatin 40 mg tablets once daily for 6 weeks
|
Baseline-Placebo
Participants receiving Placebo once daily for 6 weeks
|
Week 4-Placebo
Participants receiving Placebo once daily for 6 weeks
|
Week 6-Placebo
Participants receiving Placebo once daily for 6 weeks
|
|---|---|---|---|---|---|---|
|
Change From Baseline to Week 6 in Plasma Levels of Vascular Endothelial Growth Factor (VEGF)
|
-3.99 pg/mL
Interval -29.4 to 7.8
|
-10.5 pg/mL
Interval -50.4 to 9.8
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, 6 weeksPopulation: Intent was to perform analysis using flow cytometry but cells did not survive thawing. Decision was made to use CBC laboratory values for absolute monocyte (AMC), lymphocyte (ALC) and neutrophil (ANC) counts to perform the analysis.
Flow cytometry will be performed to assess absolute cell counts at baseline and at 6 weeks of treatment.
Outcome measures
| Measure |
Atorvastatin
n=13 Participants
Participants who received Atorvastatin 40 mg tablet in either the first or the second intervention
|
Placebo
n=12 Participants
Participants who received placebo tablet (matching Atorvastatin 40 mg) in either the first or the second intervention
|
Week 6-Atorvastatin
Participants receiving Atorvastatin 40 mg tablets once daily for 6 weeks
|
Baseline-Placebo
Participants receiving Placebo once daily for 6 weeks
|
Week 4-Placebo
Participants receiving Placebo once daily for 6 weeks
|
Week 6-Placebo
Participants receiving Placebo once daily for 6 weeks
|
|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Week 6 in Absolute Cell Counts
AMC
|
-0.07 10^9 cells/L
Interval -0.26 to 0.12
|
0.15 10^9 cells/L
Interval -0.11 to 0.41
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Week 6 in Absolute Cell Counts
ALC
|
0.08 10^9 cells/L
Interval -0.34 to 0.49
|
-0.22 10^9 cells/L
Interval -0.85 to 0.42
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Week 6 in Absolute Cell Counts
ANC
|
-0.18 10^9 cells/L
Interval -0.96 to 0.61
|
-0.55 10^9 cells/L
Interval -1.91 to 0.81
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, 6 weeksPopulation: The stored samples did not survive the freeze/thaw process and as such, this data was not attainable.
Flow cytometry will be performed to assess TF expression at baseline and at 6 weeks of treatment.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, 6 weeksPopulation: The stored samples did not survive the freeze/thaw process and as such, this data was not attainable.
Flow cytometry will be performed to assess TF-mediated sFLT release from monocytes at baseline and at 6 weeks of treatment.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Week 6Echocardiogram will be used to assess TR jet before and after treatment.
Outcome measures
| Measure |
Atorvastatin
n=13 Participants
Participants who received Atorvastatin 40 mg tablet in either the first or the second intervention
|
Placebo
n=13 Participants
Participants who received placebo tablet (matching Atorvastatin 40 mg) in either the first or the second intervention
|
Week 6-Atorvastatin
Participants receiving Atorvastatin 40 mg tablets once daily for 6 weeks
|
Baseline-Placebo
Participants receiving Placebo once daily for 6 weeks
|
Week 4-Placebo
Participants receiving Placebo once daily for 6 weeks
|
Week 6-Placebo
Participants receiving Placebo once daily for 6 weeks
|
|---|---|---|---|---|---|---|
|
Change From Baseline to Week 6 in Tricuspid Regurgitant (TR) Jet.
|
0.80 m/sec
Interval -1.64 to 3.24
|
-0.05 m/sec
Interval -0.69 to 0.56
|
—
|
—
|
—
|
—
|
Adverse Events
Atorvastatin
Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths
Placebo
Serious events: 3 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Atorvastatin
n=13 participants at risk
Participants who received Atorvastatin 40 mg tablet in either the first or the second intervention
|
Placebo
n=13 participants at risk
Participants who received placebo tablet (matching Atorvastatin 40 mg) in either the first or the second intervention
|
|---|---|---|
|
Vascular disorders
Pain Crisis
|
7.7%
1/13 • Number of events 1 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
23.1%
3/13 • Number of events 3 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
|
Cardiac disorders
Heart Palpitations and Fainting
|
0.00%
0/13 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
7.7%
1/13 • Number of events 1 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
Other adverse events
| Measure |
Atorvastatin
n=13 participants at risk
Participants who received Atorvastatin 40 mg tablet in either the first or the second intervention
|
Placebo
n=13 participants at risk
Participants who received placebo tablet (matching Atorvastatin 40 mg) in either the first or the second intervention
|
|---|---|---|
|
Infections and infestations
Influenza B
|
0.00%
0/13 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
7.7%
1/13 • Number of events 1 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
|
General disorders
Headaches/Head Pressure
|
15.4%
2/13 • Number of events 3 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
0.00%
0/13 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
|
Vascular disorders
Pain Crisis Treated at Home
|
7.7%
1/13 • Number of events 1 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
15.4%
2/13 • Number of events 2 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
|
General disorders
Dry Skin
|
0.00%
0/13 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
15.4%
2/13 • Number of events 2 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
|
Vascular disorders
Edema of Lower Extremity
|
7.7%
1/13 • Number of events 1 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
7.7%
1/13 • Number of events 1 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
|
Vascular disorders
Leg Ulcer
|
0.00%
0/13 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
7.7%
1/13 • Number of events 1 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
7.7%
1/13 • Number of events 1 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
7.7%
1/13 • Number of events 2 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/13 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
7.7%
1/13 • Number of events 1 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Low O2 Saturation
|
7.7%
1/13 • Number of events 1 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
0.00%
0/13 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
|
Gastrointestinal disorders
Nausea and Diarrhea
|
0.00%
0/13 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
7.7%
1/13 • Number of events 2 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
|
Blood and lymphatic system disorders
Low ANC
|
0.00%
0/13 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
7.7%
1/13 • Number of events 1 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
|
General disorders
Axillary Adenopathy
|
15.4%
2/13 • Number of events 2 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
0.00%
0/13 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
|
General disorders
Dizziness
|
7.7%
1/13 • Number of events 1 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
0.00%
0/13 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
|
Renal and urinary disorders
Urinary Tract Infection
|
7.7%
1/13 • Number of events 1 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
0.00%
0/13 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.00%
0/13 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
7.7%
1/13 • Number of events 1 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
|
Musculoskeletal and connective tissue disorders
Left Wrist Pain
|
7.7%
1/13 • Number of events 1 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
0.00%
0/13 • Beginning with the first intervention and throughout washout and second intervention and then for 4 weeks after end of treatment
|
Additional Information
Kenneth Ataga, MD
University of North Carolina at Chapel Hill
Phone: 901-448-2813
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place