Modulation of Monocyte Activation by Atorvastatin in HIV Infection

NCT ID: NCT01263938

Last Updated: 2019-05-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2017-10-31

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.

Conditions

HIV Dementia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Atorvastatin

Group Type: OTHER

Atorvastatin

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Lipitor

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ronald G Collman, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

University of Pennsylvania School of Medicine

Philadelphia, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

P30AI045008

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB Protocol #: 812196

Identifier Type: -

Identifier Source: org_study_id