Mitochondrial Oxidative Stress and Vascular Health in Chronic Kidney Disease

• ClinicalTrials.gov Identifier: NCT02364648
• Recruitment Status: Unknown
• First Posted: February 18, 2015
• Last Update Posted: April 25, 2019
• Sponsor: University of Delaware
• Information provided by (Responsible Party): David Edwards, University of Delaware

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Chronic Kidney Disease	Dietary Supplement: MitoQ; Dietary Supplement: Placebo	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Mitochondrial Oxidative Stress and Vascular Health in Chronic Kidney Disease
• Actual Study Start Date: July 1, 2017
• Estimated Primary Completion Date: August 30, 2019
• Estimated Study Completion Date: September 30, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Microvascular Function, assessed by laser Doppler flowmetry coupled with microdialysis [ Time Frame: Change from baseline at 4 weeks ]
   Nitric oxide mediated cutaneous microvascular dilatory response to local heating assessed by laser Doppler flowmetry coupled with microdialysis

Secondary Outcome Measures :

1. Conduit artery endothelial dependent dilation, assessed by duplex ultrasound [ Time Frame: Change from baseline at 4 weeks ]
   Brachial artery flow mediated dilation assessed by duplex ultrasound
2. Mitochondria derived superoxide, assessed by electron paramagnetic resonance spectroscopy [ Time Frame: Change from baseline at 4 weeks ]
   Plasma mitochondria superoxide assessed by electron paramagnetic resonance spectroscopy

Other Outcome Measures:

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Danielle L Kirkman, PhD; 302 831 4659; dkirkman@udel.edu

Contact: David G Edwards, PhD; dge@udel.edu

Locations

United States, Delaware

Department of Kinesiology and Applied Physiology, University of Delaware; Recruiting

Newark, Delaware, United States, 19713

Contact: David Edwards, PhD dge@udel.edu

Contact: Danielle Kirkman, PhD dkirkman@udel.edu

Principal Investigator: Danielle Kirkman, PhD

Principal Investigator: David Edwards, PhD

Sponsors and Collaborators

University of Delaware

Investigators

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

More Information

• Responsible Party: David Edwards, Associate Professor, University of Delaware
• ClinicalTrials.gov Identifier: NCT02364648
• Other Study ID Numbers: 680076-2
• First Posted: February 18, 2015
• Last Update Posted: April 25, 2019
• Last Verified: April 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by David Edwards, University of Delaware:

Endothelium, vascular; MitoQ; Mitochondria; Oxidative Stress; Chronic Renal Insufficiency; Cardiovascular Disease

Additional relevant MeSH terms:

Kidney Diseases; Renal Insufficiency, Chronic; Urologic Diseases; Renal Insufficiency