Mitochondrial Oxidative Stress and Vascular Health in Chronic Kidney Disease

The purpose of this study is to examine the effect of mitochondria derived oxidative stress on vascular function in patients with moderate to severe Chronic Kidney Disease.

Study Overview

• Status: Unknown
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: MitoQ

Detailed Description

Chronic Kidney Disease (CKD) patients are at increased risk of cardiovascular disease. Endothelial dysfunction, characterized by a reduced bioavailability in nitric oxide, is an independent predictor of cardiovascular disease in CKD. Increased oxidative stress is a potential cause of endothelial dysfunction in this patient cohort. This study investigates the role that mitochondrial derived oxidative stress plays in CKD related vascular dysfunction. In a controlled, double blinded trial, Stage 3-5 CKD patients will be randomly assigned to receive a 4 week daily dose of a mitochondria targeted antioxidant (MitoQ) or a placebo.

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Delaware
    • Newark, Delaware, United States, 19713
      • Recruiting
      • Department of Kinesiology and Applied Physiology, University of Delaware
      • Contact: David Edwards, PhD; Email: dge@udel.edu
      • Contact: Danielle Kirkman, PhD; Email: dkirkman@udel.edu
      • Principal Investigator: Danielle Kirkman, PhD
      • Principal Investigator: David Edwards, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Stage 3 - 5 Chronic Kidney Disease

Exclusion Criteria:

• History of cardiovascular disease;
• Current pregnancy;
• Uncontrolled hypertension;
• Uncontrolled hyperlipidemia;
• Current hormone replacement therapy;
• Current use of tobacco products;
• Elevated liver enzymes;
• Current autoimmune disease;
• Daily use of of antioxidants >300mg

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MitoQ; 4 week 20mg oral daily dose of MitoQ	Dietary supplement: MitoQ; Mitochondria targeted antioxidant
Placebo Comparator: Placebo; 4 week 20mg oral daily placebo	Dietary supplement: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microvascular Function, assessed by laser Doppler flowmetry coupled with microdialysis	Nitric oxide mediated cutaneous microvascular dilatory response to local heating assessed by laser Doppler flowmetry coupled with microdialysis	Change from baseline at 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Conduit artery endothelial dependent dilation, assessed by duplex ultrasound	Brachial artery flow mediated dilation assessed by duplex ultrasound	Change from baseline at 4 weeks
Mitochondria derived superoxide, assessed by electron paramagnetic resonance spectroscopy	Plasma mitochondria superoxide assessed by electron paramagnetic resonance spectroscopy	Change from baseline at 4 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endothelial cell NADPH oxidase expression	NADPH oxidase expression in human endothelial cll expression	Change from baseline at 4 weeks
Arterial Stiffness, assessed by central blood pressure, augmentation index and carotid artery to femoral artery pulse wave velocity	Central blood pressure, augmentation index and carotid artery to femoral artery pulse wave velocity	Change from baseline at 4 weeks
Ambulatory Blood Pressure	2h hour continuous ambulatory blood pressure monitoring	Change from baseline at 4 weeks
Habitual Physical Activity, assessed by accelerometry	Daily habitual physical activity assessed by accelerometry	Change from baseline at 4 weeks

Collaborators and Investigators

• Sponsor: University of Delaware
• Investigators: Principal Investigator: David G Edwards, PhD, University of Delaware; Principal Investigator: Danielle L Kirkman, PhD, University of Delaware

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2017
• Primary Completion (Anticipated): August 30, 2019
• Study Completion (Anticipated): September 30, 2019

Study Registration Dates

• First Submitted: February 10, 2015
• First Submitted That Met QC Criteria: February 17, 2015
• First Posted (Estimate): February 18, 2015

Study Record Updates

• Last Update Posted (Actual): April 25, 2019
• Last Update Submitted That Met QC Criteria: April 24, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Cardiovascular Disease; Oxidative Stress; Mitochondria; Chronic Renal Insufficiency; MitoQ; Endothelium, vascular
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: 680076-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No