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| ID | Type | Description | Link |
|---|---|---|---|
| P30AI045008 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) | NIH |
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Activated monocytes play a key role in the pathogenesis of HIV-associated neurocognitive disorders (HAND). Individuals with HAND have expanded populations of activated monocytes. These monocytes are thought to emigrate into the CNS, where they produce neurotoxic proinflammatory factors, and also carry virus into the CNS. Statins are cholesterol lowering drugs with pleiotropic immunomodulatory / anti-inflammatory properties that are currently being explored for immunomodulation of T cell activation in several diseases, in addition to their established role to treat hyperlipidemia and atherosclerosis. The investigators in vitro data suggests that these drugs can downregulate monocyte activation patterns seen in HIV infection. No in vivo studies have yet been carried out to assess the effects of statins on the pro-inflammatory monocyte population in chronic HIV disease. This will be a pilot study of whether statin treatment will reduce the inflammatory monocyte phenotype and downregulate the inflammatory cytokines that have been linked to neuropathogenesis in HIV infection. If so, they may have potential as adjunctive therapy in HIV-associated neurological disease. The investigators propose to:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Atorvastatin | Other |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atorvastatin | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Monocyte Surface Markers Expression (Expressed as Percentage), Following Treatment of Chronic HIV+/ HAART+ Subjects With Atorvastatin (T=12wks Versus T=0wk). | 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. | 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) |
| Change From Baseline in Levels of Plasma Inflammatory Marker MCP-1 of Chronic HIV+/ HAART+ Subjects. | 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. | 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) |
| Change From Baseline in Levels of Plasma Inflammatory Marker sCD14 of Chronic HIV+/ HAART+ Subjects. | 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. | 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) |
| Change From Baseline in Levels of Plasma Inflammatory Marker sCD163 of Chronic HIV+/ HAART+ Subjects. | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ronald G Collman, MD | University of Pennsylvania | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pennsylvania School of Medicine | Philadelphia | Pennsylvania | 19104 | United States |
Enrolled participants were assigned to treatment groups based on the nature of HAART therapy (PI- or non-PI based).
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Atorvastatin | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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.
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| ID | Title | Description |
|---|---|---|
| BG000 | Atorvastatin | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Monocyte Surface Markers Expression (Expressed as Percentage), Following Treatment of Chronic HIV+/ HAART+ Subjects With Atorvastatin (T=12wks Versus T=0wk). | 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. | 1) Percentage of peripheral blood monocyte surface markers: CD16, CD163, CCR2 | Posted | Mean | Standard Deviation | Change T=0 to T=12 (percentage change) | 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) |
|
Data was collected over a period of sixteen weeks.
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Atorvastatin | 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. |
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This study had a very small sample size of 5 subjects. Therefore due to lack of power the data is inconclusive.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Ronald Collman | University of Pennsylvania School of Medicine | 215-898-0193 | collmanr@pennmedicine.upenn.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 5, 2011 | Mar 26, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D015526 | AIDS Dementia Complex |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D000069059 | Atorvastatin |
| ID | Term |
|---|---|
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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|
| 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) |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG000 |
| Atorvastatin |
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. |
|
|
|
| Primary | Change From Baseline in Levels of Plasma Inflammatory Marker MCP-1 of Chronic HIV+/ HAART+ Subjects. | 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. | Plasma MCP-1 levels | Posted | Mean | Standard Deviation | pg/ml (Change from T0 to T12) | 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) |
|
|
|
|
| Primary | Change From Baseline in Levels of Plasma Inflammatory Marker sCD14 of Chronic HIV+/ HAART+ Subjects. | 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. | Plasma sCD14 levels | Posted | Mean | Standard Deviation | ug/ml (Change fromT=0 to T=12wk) | 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) |
|
|
|
|
| Primary | Change From Baseline in Levels of Plasma Inflammatory Marker sCD163 of Chronic HIV+/ HAART+ Subjects. | 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. | Plasma sCD163 levels | Posted | Mean | Standard Deviation | ng/ml (Change fromT=0 to T=12wk) | 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) |
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|
|
| 0 |
| 5 |
| 0 |
| 5 |
| 0 |
| 5 |
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| D015229 |
| Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006538 |
| Heptanoic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |