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

Primary Purpose

Kidney Failure, Chronic, Cardiovascular Disease, Arteriosclerosis

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Hydroxychloroquine
Matching Placebo
Sponsored by
University of Arkansas
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Kidney Failure, Chronic focused on measuring Kidney Failure, Chronic, Cardiovascular Disease, Arteriosclerosis

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Central Arkansas Veterans Healthcare System
  • University of Arkansas for Medical Sciences
  • University of Florida

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Matching Placebo

Hydroxychloroquine

Arm Description

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)

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)

Outcomes

Primary Outcome Measures

Change From Baseline in Inflammatory Marker, Hs-C Reactive Protein, at 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.

Secondary Outcome Measures

Full Information

First Posted
February 10, 2012
Last Updated
November 18, 2014
Sponsor
University of Arkansas
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1. Study Identification

Unique Protocol Identification Number
NCT01537315
Brief Title
Hydroxychloroquine in Cardiovascular Disease in Patients With Chronic Kidney Disease: A Proof of Concept Study
Official Title
Hydroxychloroquine in Cardiovascular Disease in Patients With Chronic Kidney Disease: A Proof of Concept Study
Study Type
Interventional

2. Study Status

Record Verification Date
November 2014
Overall Recruitment Status
Terminated
Why Stopped
lack of funding
Study Start Date
February 2012 (undefined)
Primary Completion Date
September 2013 (Actual)
Study Completion Date
September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Arkansas

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Failure, Chronic, Cardiovascular Disease, Arteriosclerosis
Keywords
Kidney Failure, Chronic, Cardiovascular Disease, Arteriosclerosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Matching Placebo
Arm Type
Placebo Comparator
Arm Description
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)
Arm Title
Hydroxychloroquine
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine
Other Intervention Name(s)
Plaquenil
Intervention Description
200 mg capsule daily for 10 +/- 4 days, then 200 mg twice daily till end of study (duration approximately 6 months)
Intervention Type
Other
Intervention Name(s)
Matching Placebo
Intervention Description
matching placebo capsule 200 mg daily for 10 +/- 4 days and thereafter 200 mg twice a day for duration of study, approximately 6 months
Primary Outcome Measure Information:
Title
Change From Baseline in Inflammatory Marker, Hs-C Reactive Protein, at 6 Months
Description
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.
Time Frame
Baseline and 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dumitru Rotaru, MD
Organizational Affiliation
University of Arkansas
Official's Role
Principal Investigator
Facility Information:
Facility Name
Central Arkansas Veterans Healthcare System
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
University of Arkansas for Medical Sciences
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610-0224
Country
United States

12. IPD Sharing Statement

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

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