Modulation of Monocyte Activation by Atorvastatin in HIV Infection

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01263938
Recruitment Status : Completed
First Posted : December 21, 2010
Last Update Posted : December 12, 2017
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
University of Pennsylvania

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.

Condition or disease Intervention/treatment Phase
HIV Dementia Drug: Atorvastatin Phase 4

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
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
Study Start Date : September 2011
Actual Primary Completion Date : October 2017
Actual Study Completion Date : October 2017

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Effect of statins on peripheral blood monocytes [ Time Frame: Subjects enrolled in the study following the screening visit will be assessed for the primary outcome measures at T=0 (drug intervention begins); T=2wks; T=6wks; T=12wks (intervention ends); T=16wks (study ends) ]

    Primary outcome measures include:

    1. Surface marker analyses of monocyte phenotype
    2. Plasma levels of soluble inflammatory mediators

Secondary Outcome Measures :
  1. Effect of statins on T cell markers [ Time Frame: Subjects enrolled in the study following the screening visit will be assessed for the secondary outcome measures at T=0 (drug intervention begins); T=2wks; T=6wks; T=12wks (intervention ends); T=16wks (study ends) ]

    Secondary outcome measures include:

    1. T cell surface markers
    2. expanded plasma cytokine profile

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01263938

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)
Principal Investigator: Ronald G Collman, MD University of Pennsylvania

Responsible Party: University of Pennsylvania Identifier: NCT01263938     History of Changes
Other Study ID Numbers: IRB Protocol #: 812196
P30AI045008 ( U.S. NIH Grant/Contract )
First Posted: December 21, 2010    Key Record Dates
Last Update Posted: December 12, 2017
Last Verified: December 2017

Keywords provided by University of Pennsylvania:

Additional relevant MeSH terms:
HIV Infections
AIDS Dementia Complex
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Atorvastatin Calcium
Anticholesteremic Agents
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors