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

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).

Inclusion Criteria:

- Measured stage IV proteinuric CKD with an estimated MDRD GFR (eGFR) of 18 to 35
ml/min.

- Current or history of documented proteinuria of more than or equal to 300 mg/dL in 24
hours or a spot urine protein to creatinine ratio of greater than 0.3 ug/mg.

- Not on dialysis.

- Ages 18 to 80 years, both sexes, all races and ethnicities

Exclusion Criteria:

- G6PD deficiency or known hypersensitivity to 4-aminoquinoline compounds (such as
chloroquine or hydroxychloroquine).

- Abnormal liver functions; AST and ALT more than 2.5 times the normal or INR without
being anti-coagulated greater than 1.4.

- Known chronic active infections like HIV, Hepatitis B or Hepatitis C positive,
chronic osteomyelitis etc.

- Recent serious infection including Pneumonia requiring hospitalization, meningitis,
septicemia in the 2 months prior to screening.

- Active or recently treated (< 1 year in remission) malignancy or systemic
inflammatory diseases (Patients with localized squamous cell carcinoma of the skin
are eligible).

- Pregnancy, breastfeeding or planning to become pregnant during the course of the
study.

- Use of systemic corticosteroids or other immunosuppression within last 3 months
(acute course of steroid for a gouty arthritis or chronic obstructive pulmonary
disease (COPD) is eligible if > 1 month ago).

- History of prolonged QTc interval > 450.

- Inability to attend or comply with treatment or follow-up scheduling.

- Life expectancy less than 6 months or uncontrolled congestive heart failure (CHF)
(defined as more than 2 admissions in prior 6 months).

- Any other condition the PI determines may put the research subject in jeopardy during
the course of the study.