Clinical Trial: Downmodulating Monocyte Activation for HIV-1 Associated Neurocognitive Disorders (HAND)

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Statin Modulation of Monocyte/Macrophage Activation for HAND Treatment

Brief Summary:

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

  1. determine how Atorvastatin modulates monocyte activation, intracellular signaling pathways and functions implicated in the pathogenesis of HAND in vitro
  2. define the effect of Atorvastatin on monocyte activation in HIV infected / ART treated subjects in a double blind, placebo controlled crossover study
  3. define gene expression patters of monocyte activation before and following statin treatment
  4. assess Atorvastatin effects on CNS immune activation markers and neurocognitive function in ART treated subjects.

Detailed Summary:
Sponsor: University of Pennsylvania

Current Primary Outcome: Effects of Atorvastatin on peripheral blood monocytes [ Time Frame: 4 years ]

  1. Peripheral blood monocyte surface markers CD16; CD14; CD163; CCR2;
  2. Plasma levels of monocyte associated inflammatory cytokines and chemokines: MCP-1; sCD14 and neopterin
  3. Monocyte gene expression patterns in ART treated HIV+ subjects.
  4. Monocyte / macrophage signaling pathways


Original Primary Outcome: Same as current

Current Secondary Outcome: Effects of Atorvastatin on T cell and CSF activation markers [ Time Frame: 4 years ]

  1. Immune activation markers in the CSF: MCP-1 and neopterin
  2. T cell activation markers: CD38 and CD25.
  3. Neurocognitive outcomes.


Original Secondary Outcome: Same as current

Information By: University of Pennsylvania

Dates:
Date Received: May 14, 2012
Date Started: January 2013
Date Completion: October 2017
Last Updated: January 13, 2017
Last Verified: January 2017