Effects of Mitochondrial-targeted Antioxidant on Mild Cognitive Impairment (MCI) Patients
Primary Purpose
Alzheimer Disease, Early Onset, Mild Cognitive Impairment
Status
Withdrawn
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
MitoQ
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Alzheimer Disease, Early Onset
Eligibility Criteria
Inclusion Criteria:
- be able to give written, informed consent
- Have a clinical diagnosis of Mild Cognitive Impairment (MCI) verified by a medical doctor
- have a stable blood pressure regimen, stable lipid regimen, stable diabetes regimen and risk factor control for 6 weeks.
- Free of kidney, metabolic or cardiovascular disease, including hypertension (stage 2) and previous cardiac events
- be between 50-85 years old
Exclusion Criteria:
- All participants must be free from smoking and alcohol abuse
- Not be taking prescription drugs (other than oral contraceptives, blood pressure lowering drugs, and metformin)
- Must not be diagnosed with Alzheimer's disease.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
MitoQ-Placebo
Placebo-MitoQ
Arm Description
Subjects will be tested on two different days, first day will be baseline and MitoQ intake, and second day will be placebo intake. Testing will take place 40-minutes after MitoQ and placebo intake. There will be a 2-week washout between testing days.
Subjects will be tested on two different days, first day will be baseline and placebo intake, and second day will be MitoQ intake. Testing will take place 40-minutes after placebo and MitoQ intake. There will be a 2-week washout between testing days.
Outcomes
Primary Outcome Measures
Carotid artery blood flow
Blood flow in the carotid artery will be measured with ultrasound
Secondary Outcome Measures
Oxidative Stress
Blood draws will be taken to measure oxidative stress markers in the blood
Cerebrovascular Oxygenation
Near-infrared spectroscopy will be used to measure cerebrovascular oxygenation
Brain Electrical Activity
EEG will measure brain electrical activity
Endothelial Function
Flow-mediated dilation will be used to measure vasodilation in the brachial artery
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03514875
Brief Title
Effects of Mitochondrial-targeted Antioxidant on Mild Cognitive Impairment (MCI) Patients
Official Title
Effects of Mitochondrial-targeted Antioxidant on Carotid Artery Endothelial Function and Brain Blood Flow in Mild Cognitive Impairment (MCI) Patients
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Withdrawn
Why Stopped
discontinued due to change in operating plans prior to study initiation and enrollment
Study Start Date
November 11, 2019 (Actual)
Primary Completion Date
July 18, 2022 (Actual)
Study Completion Date
July 18, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Nebraska
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Neurodegenerative diseases such as Mild Cognitive Impairment, Alzheimer's, and dementia affect millions of Americans. Although these diseases are heavily researched, there is very little research examining the impact of attenuated carotid artery endothelial function and cerebrovascular blood flow on cognitive function. This is surprising, as cerebrovascular oxygenation has been shown to be strongly associated with reduced cognitive function and the pathogenesis of neurodegenerative diseases. For example, hypertension, diabetes, and high cholesterol have been shown to increase the risk of Alzheimers related dementia. Therefore, the purpose of this proposed study will be to examine the effects of MitoQ supplementation on carotid artery vasodilatory function and cerebrovascular blood flow in those suffering from Mild Cognitive Impairment (MCI). MitoQ is a mitochondria-targeting antioxidant that can improve nitric oxide production in the blood vessel, which should improve endothelial function, and thus cerebrovascular blood flow.
Detailed Description
Metabolic disease parameters, such as hyperlipidemia and hypertension have been observed in Alzheimer's disease and dementia. The causes of neurodegenerative diseases like Alzheimers are not completely understood. However, increasing amounts of evidence are pointing to vascular dysfunction as a cause of this disease. Known as the vascular hypothesis, pathology is suggested to begin with cerebral hypoperfusion through attenuated blood flow via clogged carotid arteries. Hypoperfusion of cerebral cells means that they do not receive enough oxygen to function optimally. This lack of oxygen is believed to lead to cognitive impairment. It is hypothesized that these metabolic conditions can damage the endothelial wall, leading to impaired vasodilation and blood flow. This damage occurs in the carotid arteries, which would limit blood flow to the brain. This impaired blood flow also results from higher levels of reactive oxygen species (ROS), which reduce the bioavailability of nitric oxide (NO), an important vasodilator. Antioxidants, such as MitoQ, reduce these ROS and thus increase the NO availability, which improves endothelial function. This study will measure the use of the antioxidant MitoQ to reduce this endothelial dysfunction, thereby improving blood flow in the carotid arteries. Blood vessel health can be measured by how much bigger or smaller a vessel can become, because the ability of the vessel to change size is very important to make sure that blood is delivered to the tissues of the body. This study is being done to help us understand if endothelial dysfunction in Mild Cognitive Impairment (MCI) patients leads to the pathogenesis of the disease.
We will examine how endothelial function and cerebrovascular blood flow changes after consumption of MitoQ. We hope to achieve this through measures of carotid artery blood flow and brachial artery blood flow, using a doppler ultrasound for both, while using flow mediated dilation when measuring the brachial artery. The flow-mediated dilation test is a validated and safe assessment of endothelial function and vascular health. The premise behind the assessment is that endothelium produces autocoids, like nitric oxide, that dilate in response to shear stress. Flow-mediated dilation has been shown to be an effective tool to assess endothelial function in the peripheral and coronary vasculature. This assessment of endothelial health can be used in healthy individuals to detect risk for cardiovascular disease. We will also utilize near infrared spectroscopy to measure tissue oxygenation in the brain, which is also a measure of improved blood flow, and will measure brain neural activity with an EEG. Finally, we will collect blood samples to measure the change in ROS levels before and after MitoQ consumption
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease, Early Onset, Mild Cognitive Impairment
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
1:1 Randomized, cross-over design
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MitoQ-Placebo
Arm Type
Experimental
Arm Description
Subjects will be tested on two different days, first day will be baseline and MitoQ intake, and second day will be placebo intake. Testing will take place 40-minutes after MitoQ and placebo intake. There will be a 2-week washout between testing days.
Arm Title
Placebo-MitoQ
Arm Type
Experimental
Arm Description
Subjects will be tested on two different days, first day will be baseline and placebo intake, and second day will be MitoQ intake. Testing will take place 40-minutes after placebo and MitoQ intake. There will be a 2-week washout between testing days.
Intervention Type
Dietary Supplement
Intervention Name(s)
MitoQ
Intervention Description
MitoQ is a mitochondria-targeting antioxidant, which should improve NO bioavailability, and therefore vasodilation
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
A placebo will be used in a double blinded, randomized, cross-over design
Primary Outcome Measure Information:
Title
Carotid artery blood flow
Description
Blood flow in the carotid artery will be measured with ultrasound
Time Frame
2 Days
Secondary Outcome Measure Information:
Title
Oxidative Stress
Description
Blood draws will be taken to measure oxidative stress markers in the blood
Time Frame
2 days
Title
Cerebrovascular Oxygenation
Description
Near-infrared spectroscopy will be used to measure cerebrovascular oxygenation
Time Frame
2 Days
Title
Brain Electrical Activity
Description
EEG will measure brain electrical activity
Time Frame
2 Days
Title
Endothelial Function
Description
Flow-mediated dilation will be used to measure vasodilation in the brachial artery
Time Frame
2 Days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
be able to give written, informed consent
Have a clinical diagnosis of Mild Cognitive Impairment (MCI) verified by a medical doctor
have a stable blood pressure regimen, stable lipid regimen, stable diabetes regimen and risk factor control for 6 weeks.
Free of kidney, metabolic or cardiovascular disease, including hypertension (stage 2) and previous cardiac events
be between 50-85 years old
Exclusion Criteria:
All participants must be free from smoking and alcohol abuse
Not be taking prescription drugs (other than oral contraceptives, blood pressure lowering drugs, and metformin)
Must not be diagnosed with Alzheimer's disease.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Song-young Park, PhD
Organizational Affiliation
University of Nebraska
Official's Role
Principal Investigator
12. IPD Sharing Statement
Citations:
PubMed Identifier
24224133
Citation
Kelleher RJ, Soiza RL. Evidence of endothelial dysfunction in the development of Alzheimer's disease: Is Alzheimer's a vascular disorder? Am J Cardiovasc Dis. 2013 Nov 1;3(4):197-226.
Results Reference
background
PubMed Identifier
16116114
Citation
Luchsinger JA, Reitz C, Honig LS, Tang MX, Shea S, Mayeux R. Aggregation of vascular risk factors and risk of incident Alzheimer disease. Neurology. 2005 Aug 23;65(4):545-51. doi: 10.1212/01.wnl.0000172914.08967.dc.
Results Reference
background
PubMed Identifier
21263128
Citation
Green DJ, Jones H, Thijssen D, Cable NT, Atkinson G. Flow-mediated dilation and cardiovascular event prediction: does nitric oxide matter? Hypertension. 2011 Mar;57(3):363-9. doi: 10.1161/HYPERTENSIONAHA.110.167015. Epub 2011 Jan 24.
Results Reference
background
PubMed Identifier
24277765
Citation
Green DJ, Dawson EA, Groenewoud HM, Jones H, Thijssen DH. Is flow-mediated dilation nitric oxide mediated?: A meta-analysis. Hypertension. 2014 Feb;63(2):376-82. doi: 10.1161/HYPERTENSIONAHA.113.02044. Epub 2013 Nov 25.
Results Reference
background
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Effects of Mitochondrial-targeted Antioxidant on Mild Cognitive Impairment (MCI) Patients
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