Clinical Trials

MainTitle

Modulation of Monocyte Activation by Atorvastatin in HIV Infection

This study has been completed
Sponsor
University of Pennsylvania

Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Information provided by (Responsible Party)
University of Pennsylvania
ClinicalTrials.gov Identifier
NCT01263938

First received: December 17, 2010
Last updated: April 17, 2019
Last Verified: April 2019
History of Changes
Purpose

Purpose

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.

Condition Intervention Phase
HIV Dementia

Drug : Atorvastatin
Phase 4

Study Type: Interventional
Study Design: Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study to Evaluate Effects of Atorvastatin on Monocyte Activation in HAART-treated HIV Infected Individuals

Further study details as provided by University of Pennsylvania:

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). [ 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) ]
    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. [ 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) ]
    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. [ 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) ]
    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. [ 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) ]
    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.

Enrollment: 5
Study Start Date: September 2011
Study Completion Date: October 2017
Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Other: Atorvastatin

Drug: 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.

Other Name: Lipitor
Eligibility

Eligibility

Ages Eligible for Study: 18 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

Inclusion Criteria:

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


Exclusion Criteria:
    1. Concomitant use of fibric acid derivatives or other lipid lowering agents including patients on statins and Ezetimibe
    2. Use of any anti-inflammatory drugs (OTC or prescription) on a daily basis
    3. Pregnancy or breast feeding
    4. 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
    5. Allergy or hypersensitivity to statins or any of its components
    6. History of myositis or rhabdomyolysis with use of any statins
    7. Patients who are on concurrent immunomodulatory agents, including systemic corticosteroids will be ineligible for 3 months after completion of therapy with the immunomodulating agents
    8. History of inflammatory muscle disease such as poly or dermatomyositis
    9. Serious intercurrent illness requiring systemic treatment and/or hospitalization within 30 days of entry
    10. Evidence of active opportunistic infections requiring treatment or neoplasms that require chemotherapy during the study period
    11. Creatine phosphokinase elevations (CPK) greater than 3 times the upper limit of normal
    12. Known active liver disease or AST/ALT greater than 2x the upper limit of normal
    13. Renal insufficiency, indicated by serum creatinine 2 mg/dl
    14. Absolute neutrophil count (ANC) 1000/mm3, hemoglobin < 10.0 g/dL for males and <9 g/dL
    for females, platelet count 100,000/mm

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01263938

Locations

United States, Pennsylvania
University of Pennsylvania School of Medicine
Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

University of Pennsylvania
National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Principal Investigator: Ronald G Collman, MD University of Pennsylvania
More Information

More Information


Responsible Party: University of Pennsylvania  
ClinicalTrials.gov Identifier: NCT01263938   History of Changes  
Other Study ID Numbers: IRB Protocol #: 812196  
  P30AI045008  
Study First Received: December 17, 2010  
Last Updated: April 17, 2019  

Keywords provided by University of Pennsylvania:

HIV
monocytes
CD16+
statins
mcp1
inflammation

Additional relevant MeSH terms:
AIDS Dementia Complex
Atorvastatin

ClinicalTrials.gov processed this data on June 01, 2020
This information is provided by ClinicalTrials.gov.