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Modulation of Monocyte Activation by Atorvastatin in HIV Infection

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ClinicalTrials.gov Identifier: NCT01263938
Recruitment Status : Completed
First Posted : December 21, 2010
Results First Posted : April 18, 2019
Last Update Posted : May 1, 2019
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
University of Pennsylvania

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition HIV Dementia
Intervention Drug: Atorvastatin
Enrollment 5
Recruitment Details Subjects were recruited from the AIDS Clinical Trial Unit (ACTU) at the Hospital of University Of Pennsylvania, Philadelphia, PA. The screening and recruitment process was carried out during the period September 2011 thru April 2012.
Pre-assignment Details Enrolled participants were assigned to treatment groups based on the nature of HAART therapy (PI- or non-PI based).
Arm/Group Title Atorvastatin
Hide Arm/Group Description

Atorvastatin: For subjects on PI-based HAART therapy: 10mg/day X 2weeks followed by 20mg/day.

For subjects on non PI-based HAART therapy: 20mg/day X 2weeks followed by 40mg/day.

Period Title: Overall Study
Started 5
Completed 5
Not Completed 0
Arm/Group Title Atorvastatin
Hide Arm/Group Description

Atorvastatin: For subjects on PI-based HAART therapy: 10mg/day X 2weeks followed by 20mg/day.

For subjects on non PI-based HAART therapy: 20mg/day X 2weeks followed by 40mg/day.

Overall Number of Baseline Participants 5
Hide Baseline Analysis Population Description
This was an open label treatment study where enrolled participants at T=12wks post-drug treatment were compared to themselves at T=0 (pre-drug treatment), to assess changes in outcome measures as a result of treatment.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants
<=18 years
0
   0.0%
Between 18 and 65 years
5
 100.0%
>=65 years
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants
Female
1
  20.0%
Male
4
  80.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race Number Analyzed 5 participants
African American
3
  60.0%
Caucasian
2
  40.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 5 participants
5
1.Primary Outcome
Title Change in Monocyte Surface Markers Expression (Expressed as Percentage), Following Treatment of Chronic HIV+/ HAART+ Subjects With Atorvastatin (T=12wks Versus T=0wk).
Hide Description Effects of Atorvastatin on immune activation associated surface markers (CD16, CD163 and CCR2) of monocytes were assessed in chronic HIV+/HAART+ subjects following 12 weeks of treatment. Whole blood drawn from these subjects were stained with fluorochrome tagged antibodies to the surface markers. Stained whole blood cells were then acquired on a flow cytometer and analyzed using the Flowjo software to determine the percentage of cells (monocytes) expressing the specific marker. This was done before starting and after completing drug treatment to assess the effect of drug.
Time Frame Subjects enrolled in the study following the screening visit were assessed for the primary outcome measures at T=0 (drug intervention begins); T=12wks (intervention ends)
Hide Outcome Measure Data
Hide Analysis Population Description
1) Percentage of peripheral blood monocyte surface markers: CD16, CD163, CCR2
Arm/Group Title Atorvastatin
Hide Arm/Group Description:

For subjects on PI-based HAART:

10mg/day X 2weeks followed by 20mg/day.

For subjects on non PI-based HAART:

20mg/day X 2weeks followed by 40mg/day.

For all subjects treatment was stopped at 12 weeks.

Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: Change T=0 to T=12 (percentage change)
Total CD14+CD16+ monocytes 1.5  (10.2)
CD14+CD163+ monocytes -4.4  (18)
CD14+CCR2+ monocytes 0.5  (7.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atorvastatin
Comments Sample size calculations were based on having sufficient power to detect a change in each of the outcome variables from baseline to week 12.The effect size was calculated as (detectable difference in change in outcome) / (SD of the change). Based on preliminary in vitro data, the smallest effect size was 1.88. Assuming that only 40% of this effect will be present in vivo (effect size=0.75), alpha = 0.05 and 80% power, n=16 is needed to complete the study.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.625
Comments Threshold for statistical significance: p<0.05
Method Wilcoxon signed rank
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Atorvastatin
Comments Sample size calculations were based on having sufficient power to detect a change in each of the outcome variables from baseline to week 12.The effect size was calculated as (detectable difference in change in outcome) / (SD of the change). Based on preliminary in vitro data, the smallest effect size was 1.88. Assuming that only 40% of this effect will be present in vivo (effect size=0.75), alpha = 0.05 and 80% power, n=16 is needed to complete the study.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.813
Comments Threshold for statistical significance: p<0.05
Method Wilcoxon signed rank
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Atorvastatin
Comments Sample size calculations were based on having sufficient power to detect a change in each of the outcome variables from baseline to week 12.The effect size was calculated as (detectable difference in change in outcome) / (SD of the change). Based on preliminary in vitro data, the smallest effect size was 1.88. Assuming that only 40% of this effect will be present in vivo (effect size=0.75), alpha = 0.05 and 80% power, n=16 is needed to complete the study.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.999
Comments Threshold for statistical significance: p<0.05
Method Wilcoxon signed rank
Comments [Not Specified]
2.Primary Outcome
Title Change From Baseline in Levels of Plasma Inflammatory Marker MCP-1 of Chronic HIV+/ HAART+ Subjects.
Hide Description Monocyte specific inflammatory soluble factor MCP-1 was measured by ELISA in plasma of HIV+/HAART+ subjects at baseline and at 12 weeks following atorvastatin treatment.
Time Frame Subjects enrolled in the study following the screening visit were assessed for the primary outcome measures at T=0 (drug intervention begins); T=12wks (intervention ends)
Hide Outcome Measure Data
Hide Analysis Population Description
Plasma MCP-1 levels
Arm/Group Title Atorvastatin
Hide Arm/Group Description:

For subjects on PI-based HAART:

10mg/day X 2weeks followed by 20mg/day.

For subjects on non PI-based HAART:

20mg/day X 2weeks followed by 40mg/day.

Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: pg/ml (Change from T0 to T12)
10  (176.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atorvastatin
Comments Sample size calculations were based on having sufficient power to detect a change in each of the outcome variables from baseline to week 12.The effect size was calculated as (detectable difference in change in outcome) / (SD of the change). Based on preliminary in vitro data, the smallest effect size was 1.88. Assuming that only 40% of this effect will be present in vivo (effect size=0.75), alpha = 0.05 and 80% power, n=16 is needed to complete the study.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.999
Comments Threshold for statistical significance: p<0.05
Method Wilcoxon signed rank
Comments [Not Specified]
3.Primary Outcome
Title Change From Baseline in Levels of Plasma Inflammatory Marker sCD14 of Chronic HIV+/ HAART+ Subjects.
Hide Description Monocyte specific inflammatory soluble factor sCD14 was measured by ELISA in plasma of HIV+/HAART+ subjects at baseline and at 12 weeks following atorvastatin treatment.
Time Frame Subjects enrolled in the study following the screening visit were assessed for the primary outcome measures at T=0 (drug intervention begins); T=12wks (intervention ends)
Hide Outcome Measure Data
Hide Analysis Population Description
Plasma sCD14 levels
Arm/Group Title Atorvastatin
Hide Arm/Group Description:

For subjects on PI-based HAART:

10mg/day X 2weeks followed by 20mg/day.

For subjects on non PI-based HAART:

20mg/day X 2weeks followed by 40mg/day.

Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: ug/ml (Change fromT=0 to T=12wk)
-0.22  (0.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atorvastatin
Comments Sample size calculations were based on having sufficient power to detect a change in each of the outcome variables from baseline to week 12.The effect size was calculated as (detectable difference in change in outcome) / (SD of the change). Based on preliminary in vitro data, the smallest effect size was 1.88. Assuming that only 40% of this effect will be present in vivo (effect size=0.75), alpha = 0.05 and 80% power, n=16 is needed to complete the study.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.813
Comments Threshold for statistical significance: p<0.05
Method Wilcoxon signed rank
Comments [Not Specified]
4.Primary Outcome
Title Change From Baseline in Levels of Plasma Inflammatory Marker sCD163 of Chronic HIV+/ HAART+ Subjects.
Hide Description Monocyte specific inflammatory soluble factor sCD163 was measured by ELISA in plasma of HIV+/HAART+ subjects at baseline and at 12 weeks following atorvastatin treatment.
Time Frame Subjects enrolled in the study following the screening visit were assessed for the primary outcome measures at T=0 (drug intervention begins); T=12wks (intervention ends)
Hide Outcome Measure Data
Hide Analysis Population Description
Plasma sCD163 levels
Arm/Group Title Atorvastatin
Hide Arm/Group Description:

For subjects on PI-based HAART:

10mg/day X 2weeks followed by 20mg/day.

For subjects on non PI-based HAART:

20mg/day X 2weeks followed by 40mg/day.

Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: ng/ml (Change fromT=0 to T=12wk)
-18  (81)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atorvastatin
Comments Sample size calculations were based on having sufficient power to detect a change in each of the outcome variables from baseline to week 12.The effect size was calculated as (detectable difference in change in outcome) / (SD of the change). Based on preliminary in vitro data, the smallest effect size was 1.88. Assuming that only 40% of this effect will be present in vivo (effect size=0.75), alpha = 0.05 and 80% power, n=16 is needed to complete the study.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.625
Comments Threshold for statistical significance: p<0.05
Method Wilcoxon signed rank
Comments [Not Specified]
Time Frame Data was collected over a period of sixteen weeks.
Adverse Event Reporting Description To determine whether an adverse event had occurred or not, regular laboratory testing as well as investigator assessment was carried out during the Study period.
 
Arm/Group Title Atorvastatin
Hide Arm/Group Description

Atorvastatin: For subjects on PI-based HAART therapy: 10mg/day X 2weeks followed by 20mg/day.

For subjects on non PI-based HAART therapy: 20mg/day X 2weeks followed by 40mg/day.

All-Cause Mortality
Atorvastatin
Affected / at Risk (%)
Total   0/5 (0.00%) 
Hide Serious Adverse Events
Atorvastatin
Affected / at Risk (%)
Total   0/5 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Atorvastatin
Affected / at Risk (%)
Total   0/5 (0.00%) 
This study had a very small sample size of 5 subjects. Therefore due to lack of power the data is inconclusive.
Certain Agreements
Principal Investigators are NOT 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Ronald Collman
Organization: University of Pennsylvania School of Medicine
Phone: 215-898-0193
EMail: collmanr@pennmedicine.upenn.edu
Layout table for additonal information
Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01263938    
Other Study ID Numbers: IRB Protocol #: 812196
P30AI045008 ( U.S. NIH Grant/Contract )
First Submitted: December 17, 2010
First Posted: December 21, 2010
Results First Submitted: February 6, 2019
Results First Posted: April 18, 2019
Last Update Posted: May 1, 2019