Hydroxychloroquine in Cardiovascular Disease in Patients With Chronic Kidney Disease: A Proof of Concept Study
Condition: Kidney Failure, Chronic; Cardiovascular Disease; Arteriosclerosis
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Failure, Chronic; Cardiovascular Diseases; Arteriosclerosis
Intervention: Hydroxychloroquine; Matching Placebo
Intervention description: 200 mg capsule daily for 10 +/- 4 days, then 200 mg twice daily till end of study (duration approximately 6 months); matching placebo capsule 200 mg daily for 10 +/- 4 days and thereafter 200 mg twice a day for duration of study, approximately 6 months
Intervention MeSH terms: Hydroxychloroquine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Kidney Failure, Chronic; Cardiovascular Disease; Arteriosclerosis

Summary:

      Presence of multiple traditional and nontraditional risk factors of atherosclerosis and
      cardiovascular disease (CVD) including inflammation in patients with chronic kidney disease
      (CKD) contribute to high CVD morbidity and mortality in this patient population.
      Additionally, the traditional approaches towards the therapy of CVD have little impact on CV
      mortality in these patients. Hydroxychloroquine (HCQ) used as anti-inflammatory in
      rheumatological disorders, has multiple beneficial properties relevant to the process of
      vascular disease. The effects of HCQ on atherosclerosis (AS) and vascular disease in CKD is
      not known yet. Thus, the study hypothesis is that HCQ treatment in individuals with CKD will
      provide clinically significant benefit in the management of CVD and will provide biological
      and functional atherosclerotic benefits.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Measured stage IV proteinuric chronic kidney disease with an estimated Modification of
             Diet in Renal Disease (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:

          -  glucose-6-phosphate dehydrogenase (G6PD) deficiency or known hypersensitivity to
             4-aminoquinoline compounds (such as chloroquine or hydroxychloroquine).

          -  Abnormal liver functions; aspartate aminotransferase (AST) and alanine
             aminotransferase (ALT) more than 2.5 times the normal or international normalized
             ratio (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 corrected QT 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.