Clinical Trial: Effect of Cenicriviroc on HIV Neurocognitive Impairment

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Randomized, Placebo-Controlled, Double-Blind, Pilot Study of CCR5/CCR2 Inhibitor Cenicriviroc (CVC) for HIV Associated Neurocognitive Disorder (HAND)

Brief Summary: The study hypothesis is that cenicriviroc will improve cognition in HIV infected individuals with cognitive impairment. The investigators will study the effect of cenicriviroc on cognition in 24 subjects over a 24 week period.

Detailed Summary:

HIV-associated neurocognitive disease (HAND), particularly in its milder form, is estimated to occur in greater than 30% of HIV infected individuals in the era of potent antiretroviral therapy. As even mild disease leads to functional consequences with decreased ability to live independently, HAND is of substantial public health concern. HIV-induced immune activation/inflammation of monocytes (MO) may be primarily responsible for the development of HAND.

Cenicriviroc is a combined CCR5 and CCR2 chemokine co-receptor antagonist. The investigators hypothesize that dual CCR5 and CCR2 blockade with the use of CVC will lead to measurable reductions in MO activation and lead to cognitive improvement by decreasing HIV infection of MO and by interrupting the trafficking of such MO into the central nervous system.

The investigators propose a single arm, 24-week trial of CVC in 24 subjects with HIV-1 infection suppressed on ART (plasma HIV RNA < 50 copies/ml) for 1 year or more with mild to moderate cognitive impairment.


Sponsor: University of Hawaii

Current Primary Outcome: Change from baseline to week 24 in Neuropsychological Performance utilizing a battery of neuropsychological tests [ Time Frame: baseline, week 24 ]

To assess 24 week change in global and domain-specific neuropsychological performance following CVC intensification


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Number of participants who experience temporary or permanent study drug discontinuation due to intolerability [ Time Frame: Up to 24 weeks ]
  • Cenicriviroc plasma drug levels [ Time Frame: week 2 ]
    plasma levels on dosage selected for patient
  • Change in plasma HIV RNA from baseline to week 24 [ Time Frame: Baseline, week 4, week 24 ]
  • Change in CD4 count from baseline to week 24 [ Time Frame: Baseline, week 24 ]
  • Change in fasting metabolic parameters (glucose, insulin, total, LDL and HDL cholesterol, triglycerides) [ Time Frame: baseline, week 24 ]
  • Number of participants who experience grade 2 or higher adverse events [ Time Frame: Up to 28 weeks ]
  • Change in total numbers of activated monocytes by flow cytometry phenotype [ Time Frame: baseline to week 24 ]
    Activated monocytes, defined by flow cytometry as blood cells bearing the CD14 surface receptor (indicating monocytes) and bearing the CD16 surface receptor (indicating activation)


Original Secondary Outcome:

  • Number of participants who experience temporary or permanent study drug discontinuation due to intolerability [ Time Frame: Up to 24 weeks ]
  • Cenicriviroc plasma drug levels [ Time Frame: week 2 ]
    plasma levels on dosage selected for patient
  • Change in plasma HIV RNA from baseline to week 24 [ Time Frame: Baseline, week 4, week 24 ]
  • Change in CD4 count from baseline to week 24 [ Time Frame: Baseline, week 24 ]
  • Change in fasting metabolic parameters (glucose, insulin, total, LDL and HDL cholesterol, triglycerides) [ Time Frame: baseline, week 24 ]
  • Number of participants who experience grade 2 or higher adverse events [ Time Frame: Up to 28 weeks ]


Information By: University of Hawaii

Dates:
Date Received: September 4, 2013
Date Started: April 2014
Date Completion:
Last Updated: March 14, 2017
Last Verified: March 2017