Hydroxychloroquine in Cardiovascular Disease in Patients With Chronic Kidney Disease: A Proof of Concept Study

• Change from baseline in aortic stiffness at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  Aortic stiffness will be measured using aortic pulse wave velocity which is a non-invasive method, much like a doppler or ultrasound.
  
  
• Change from baseline in endothelial injury and/or dysfunction in 6 months as measured by sVCAM-1 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  
• Change from baseline in inflammatory markers such as IL-6, hs-CRP and oxidative stress at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  These markers are measured by ELISA assays from serum.
  
  
• Change from baseline in other markers of CVD such as cardiac troponin-T at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  
• Progression of chronic kidney disease measured by a decline from baseline glomerular filtration rate at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  

• Change in baseline relevant cardiac markers of injury at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  Markers to be measured are Asymmetrical Dimethylarginine, HDL, LDL, N-Terminal proBNP.
  
  
• Change in baseline systolic blood pressure and pulse pressure at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  
• Primary non-fatal cardiovascular events such as MI or stroke at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  
• Cardiovascular mortality: Primary cause of death due to acute cardiac events including MI, stroke, sudden cardiac death and CHF at 6 months. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  
• Change in baseline proteinuria at 6 months. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  
• Change from baseline need for ESA or change in dose at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  
• Initiation of dialysis within 6 months of baseline [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  
• All-cause mortality including incidence of sepsis including any mortality related to sepsis within 6 months of baseline. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  
• Change in baseline renal function as measured by MDRD eGFR and cystatin C at 6 months. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  

This pilot study has been designed to look at the impact of hydroxychloroquine (HCQ) in the clinical model of accelerated atherosclerosis (AS) in the CKD population. This intervention is designed to have an impact on the initiation and progression of AS by reducing systemic inflammation, improving or restoring vascular endothelial function, and by improving the milieu of metabolic syndrome and insulin resistance.

The current study is a proof of concept study for the expansion of the use of HCQ for a new indication for the treatment of AS and CVD in patients with CKD. UAMS has filed an IND for a new indication on 4/28/11. The FDA responded that this study is exempt from an IND.

This "Proof-of-Concept" randomized double blinded placebo controlled study will evaluate the nature and extent of HCQ effects, and if found significantly beneficial, it will be used to guide the development of a large, multicenter, randomized control trial of HCQ to examine the hard clinical end points of CVD and mortality in patients with advanced CKD. The investigators propose to enroll 62 subjects to achieve the effects of HCQ in 52 individuals (39 HCQ group and 13 placebo group).