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Modulation of Monocyte Activation by Atorvastatin in HIV Infection

Primary Purpose

HIV Dementia

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Atorvastatin

About this trial

This is an interventional treatment trial for HIV Dementia focused on measuring HIV, monocytes, CD16+, statins, mcp1, inflammation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Chronic HIV-1 infected individuals presently on HAART with no change in drug combination for at least 3 months at time of enrollment
Plasma viral load <200 copies / ml for at least 6 months prior to enrollment in the study
CD4 T cell count more than 350/ul
Willingness to use a method of contraception during the study period
Willingness to have blood drawn
If female, willingness to undergo pregnancy testing on a monthly basis and are not breastfeeding
Ability to understand and willingness to sign the informed consent
hs-CRP levels above the upper limit of normal (>3mg/L)

Exclusion Criteria:

Concomitant use of fibric acid derivatives or other lipid lowering agents including patients on statins and Ezetimibe
Use of any anti-inflammatory drugs (OTC or prescription) on a daily basis
Pregnancy or breast feeding
Active drug use or alcohol abuse/dependence, which in the opinion of the investigators will interfere with the patient's ability to participate in the study
Allergy or hypersensitivity to statins or any of its components
History of myositis or rhabdomyolysis with use of any statins
Patients who are on concurrent immunomodulatory agents, including systemic corticosteroids will be ineligible for 3 months after completion of therapy with the immunomodulating agents
History of inflammatory muscle disease such as poly or dermatomyositis
Serious intercurrent illness requiring systemic treatment and/or hospitalization within 30 days of entry
Evidence of active opportunistic infections requiring treatment or neoplasms that require chemotherapy during the study period
Creatine phosphokinase elevations (CPK) greater than 3 times the upper limit of normal
Known active liver disease or AST/ALT greater than 2x the upper limit of normal
Renal insufficiency, indicated by serum creatinine 2 mg/dl
Absolute neutrophil count (ANC) 1000/mm3, hemoglobin < 10.0 g/dL for males and <9 g/dL for females, platelet count 100,000/mm

Sites / Locations

University of Pennsylvania School of Medicine

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Atorvastatin

Arm Description

Outcomes

Primary Outcome Measures

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.

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.

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.

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT01263938

First Posted

December 17, 2010

Last Updated

April 17, 2019

Sponsor

University of Pennsylvania

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

1. Study Identification

Unique Protocol Identification Number

NCT01263938

Brief Title

Modulation of Monocyte Activation by Atorvastatin in HIV Infection

Official Title

Pilot Study to Evaluate Effects of Atorvastatin on Monocyte Activation in HAART-treated HIV Infected Individuals

Study Type

Interventional

2. Study Status

Record Verification Date

April 2019

Overall Recruitment Status

Completed

Study Start Date

September 2011 (undefined)

Primary Completion Date

October 2017 (Actual)

Study Completion Date

October 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Pennsylvania

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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: Determine the effect of Atorvastatin on peripheral blood monocyte populations in a 12-week pilot study in chronically HIV-infected people on HAART therapy. Determine the relationship between changes in monocyte phenotype following Atorvastatin treatment, and soluble markers of activation/inflammation linked to neuropathogenesis, as well as activation status of T cells.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV Dementia

Keywords

HIV, monocytes, CD16+, statins, mcp1, inflammation

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

5 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Atorvastatin

Arm Type

Other

Intervention Type

Drug

Intervention Name(s)

Atorvastatin

Other Intervention Name(s)

Lipitor

Intervention Description

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.

Primary Outcome Measure Information:

Title

Change in Monocyte Surface Markers Expression (Expressed as Percentage), Following Treatment of Chronic HIV+/ HAART+ Subjects With Atorvastatin (T=12wks Versus T=0wk).

Description

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)

Title

Change From Baseline in Levels of Plasma Inflammatory Marker MCP-1 of Chronic HIV+/ HAART+ Subjects.

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)

Title

Change From Baseline in Levels of Plasma Inflammatory Marker sCD14 of Chronic HIV+/ HAART+ Subjects.

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)

Title

Change From Baseline in Levels of Plasma Inflammatory Marker sCD163 of Chronic HIV+/ HAART+ Subjects.

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)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Chronic HIV-1 infected individuals presently on HAART with no change in drug combination for at least 3 months at time of enrollment Plasma viral load <200 copies / ml for at least 6 months prior to enrollment in the study CD4 T cell count more than 350/ul Willingness to use a method of contraception during the study period Willingness to have blood drawn If female, willingness to undergo pregnancy testing on a monthly basis and are not breastfeeding Ability to understand and willingness to sign the informed consent hs-CRP levels above the upper limit of normal (>3mg/L) Exclusion Criteria: Concomitant use of fibric acid derivatives or other lipid lowering agents including patients on statins and Ezetimibe Use of any anti-inflammatory drugs (OTC or prescription) on a daily basis Pregnancy or breast feeding Active drug use or alcohol abuse/dependence, which in the opinion of the investigators will interfere with the patient's ability to participate in the study Allergy or hypersensitivity to statins or any of its components History of myositis or rhabdomyolysis with use of any statins Patients who are on concurrent immunomodulatory agents, including systemic corticosteroids will be ineligible for 3 months after completion of therapy with the immunomodulating agents History of inflammatory muscle disease such as poly or dermatomyositis Serious intercurrent illness requiring systemic treatment and/or hospitalization within 30 days of entry Evidence of active opportunistic infections requiring treatment or neoplasms that require chemotherapy during the study period Creatine phosphokinase elevations (CPK) greater than 3 times the upper limit of normal Known active liver disease or AST/ALT greater than 2x the upper limit of normal Renal insufficiency, indicated by serum creatinine 2 mg/dl Absolute neutrophil count (ANC) 1000/mm3, hemoglobin < 10.0 g/dL for males and <9 g/dL for females, platelet count 100,000/mm

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ronald G Collman, MD

Organizational Affiliation

University of Pennsylvania

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Pennsylvania School of Medicine

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Modulation of Monocyte Activation by Atorvastatin in HIV Infection

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