Modulation of Monocyte Activation by Atorvastatin in HIV Infection

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT01263938
First received: December 17, 2010
Last updated: November 12, 2013
Last verified: November 2013
  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: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study to Evaluate Effects of Atorvastatin on Monocyte Activation in HAART-treated HIV Infected Individuals

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]

    Primary outcome measures include:

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


Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]

    Secondary outcome measures include:

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


Estimated Enrollment: 15
Study Start Date: September 2011
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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
Investigators
Principal Investigator: Ronald G Collman, MD University of Pennsylvania
  More Information

No publications provided

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: November 12, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Pennsylvania:
HIV
monocytes
CD16+
statins
mcp1
inflammation

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

ClinicalTrials.gov processed this record on July 24, 2014