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

November 18, 2014 updated by: University of Arkansas
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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

This pilot study has been designed to look at the impact of hydroxychloroquine (HCQ) in the clinical model of accelerated atherosclerosis (AS) in the chronic kidney disease (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 cardiovascular disease (CVD) in patients with CKD.University of Arkansas for Medical Sciences (UAMS) has filed an Investigational New Drug (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).

Study Type

Interventional

Enrollment (Actual)

8

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas for Medical Sciences
      • Little Rock, Arkansas, United States, 72205
        • Central Arkansas Veterans Healthcare System
    • Florida
      • Gainesville, Florida, United States, 32610-0224
        • University of Florida

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Matching Placebo
Patients with cardiovascular disease (CVD) and chronic kidney disease (CKD) will be randomized to either hydroxychloroquine (HCQ) or matching placebo in a 3:1 ratio (approximately 39 to HCQ and 13 to placebo)
Other: Matching Placebo
matching placebo capsule 200 mg daily for 10 +/- 4 days and thereafter 200 mg twice a day for duration of study, approximately 6 months
Experimental: Hydroxychloroquine
Patients with cardiovascular disease (CVD) and chronic kidney disease (CKD) will be randomized to either hydroxychloroquine (HCQ) or matching placebo in a 3:1 ratio (approximately 39 to HCQ and 13 to placebo)
Drug: Hydroxychloroquine
200 mg capsule daily for 10 +/- 4 days, then 200 mg twice daily till end of study (duration approximately 6 months)
Other Names:
  • Plaquenil

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Inflammatory Marker, Hs-C Reactive Protein, at 6 Months
Time Frame: Baseline and 6 months
Hs-CRP will be measured at baseline (before study drug) and at end of study (6 months). This marker is measured by ELISA assay from serum.
Baseline and 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Arkansas

Investigators

  • Principal Investigator: Dumitru Rotaru, MD, University of Arkansas

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2012

Primary Completion (Actual)

September 1, 2013

Study Completion (Actual)

September 1, 2013

Study Registration Dates

First Submitted

February 10, 2012

First Submitted That Met QC Criteria

February 22, 2012

First Posted (Estimate)

February 23, 2012

Study Record Updates

Last Update Posted (Estimate)

November 19, 2014

Last Update Submitted That Met QC Criteria

November 18, 2014

Last Verified

November 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 132036

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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