Downmodulating Monocyte Activation for HIV-1 Associated Neurocognitive Disorders (HAND)
HIV associated neurological disorders (HAND), are a major problem even in ART treated people. HAND results from chronic inflammation which is largely attributed to expansion and activation of monocytes. These activated monocytes, some of which also carry virus to the brain, invade the CNS and release cytokines / chemokines resulting in further recruitment of monocytes, as well as release viral proteins which injure neurons and cause activation of other brain cells. Persistent monocyte/macrophage activation is thus a potential critical target for adjunctive therapy to treat or prevent HAND. The investigators therefore propose to study the effects of a statin drug (Atorvastatin), which has anti-inflammatory functions, on the monocyte activation status in vitro and in ART treated HIV+ individuals.
The investigators objectives are based on the hypothesis that Atorvastatin treatment will reduce the inflammatory and activated phenotype and function of monocytes which have been linked to HIV associated neuropathogenesis and occur in HIV infected subjects despite ART. In this study the investigators propose to
- determine how Atorvastatin modulates monocyte activation, intracellular signaling pathways and functions implicated in the pathogenesis of HAND in vitro
- define the effect of Atorvastatin on monocyte activation in HIV infected / ART treated subjects in a double blind, placebo controlled crossover study
- define gene expression patters of monocyte activation before and following statin treatment
- assess Atorvastatin effects on CNS immune activation markers and neurocognitive function in ART treated subjects.
Drug: Atorvastatin (generic Lipitor)
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||Statin Modulation of Monocyte/Macrophage Activation for HAND Treatment|
- Effects of Atorvastatin on peripheral blood monocytes [ Time Frame: 4 years ] [ Designated as safety issue: No ]
- Peripheral blood monocyte surface markers CD16; CD14; CD163; CCR2;
- Plasma levels of monocyte associated inflammatory cytokines and chemokines: MCP-1; sCD14 and neopterin
- Monocyte gene expression patterns in ART treated HIV+ subjects.
- Monocyte / macrophage signaling pathways
- Effects of Atorvastatin on T cell and CSF activation markers [ Time Frame: 4 years ] [ Designated as safety issue: No ]
- Immune activation markers in the CSF: MCP-1 and neopterin
- T cell activation markers: CD38 and CD25.
- Neurocognitive outcomes.
|Study Start Date:||January 2013|
|Estimated Study Completion Date:||October 2016|
|Estimated Primary Completion Date:||October 2016 (Final data collection date for primary outcome measure)|
|Active Comparator: Atorvastatin||
Drug: Atorvastatin (generic Lipitor)
Atorvastatin is an FDA approved prescription drug which is frequently used to lower cholesterol levels.It is available in the form of tablets ranging in dose from 10-80mg.
|Placebo Comparator: Placebo||
A substance containing no medication and prescribed or given to reinforce a patient's expectation to get well.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01600170
|Contact: Joseph Quinn, RNemail@example.com|
|Contact: Aleshia Thomas, RNfirstname.lastname@example.org|
|United States, Pennsylvania|
|University of Pennsylvania School of Medicine||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|Principal Investigator:||Ronald G Collman, MD||University of Pennsylvania|