Alzheimer Disease, Early OnsetNCT03514875
Effects of Mitochondrial-targeted Antioxidant on Mild Cognitive Impairment (MCI) Patients
A study testing MitoQ in people with Alzheimer Disease, Early Onset and Mild Cognitive Impairment, run by University of Nebraska.
Trial 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… Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Alzheimer Disease, Early Onset, Mild Cognitive Impairment
- What is being tested?
- MitoQ
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 11 Nov 2019to 18 Jul 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
About this study
Official title: Effects of Mitochondrial-targeted Antioxidant on Carotid Artery Endothelial Function and Brain Blood Flow in Mild Cognitive Impairment (MCI) Patients
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.
Read the 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
- Being tested
- MitoQ, Placebo
- Medical subject headings
- Alzheimer Disease, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MitoQDietary supplement
MitoQ is a mitochondria-targeting antioxidant, which should improve NO bioavailability, and therefore vasodilation
PlaceboDietary supplement
A placebo will be used in a double blinded, randomized, cross-over design
| Study group | Role | What they receive |
|---|---|---|
| MitoQ-Placebo | Experimental | 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. Receives: Dietary Supplement: MitoQ; Dietary Supplement: Placebo |
| Placebo-MitoQ | Experimental | 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. Receives: Dietary Supplement: MitoQ; Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Carotid artery blood flow
Blood flow in the carotid artery will be measured with ultrasound
Measured: 2 Days
Secondary outcomes (4)
Oxidative Stress
Blood draws will be taken to measure oxidative stress markers in the blood
Measured: 2 days
Cerebrovascular Oxygenation
Near-infrared spectroscopy will be used to measure cerebrovascular oxygenation
Measured: 2 Days
Brain Electrical Activity
EEG will measure brain electrical activity
Measured: 2 Days
Endothelial Function
Flow-mediated dilation will be used to measure vasodilation in the brachial artery
Measured: 2 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2018
- Study start11 Nov 2019
- Primary completion18 Jul 2022
- Study completion18 Jul 2022
Why it stopped: discontinued due to change in operating plans prior to study initiation and enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Alzheimer Disease, Early OnsetStudies of the same condition, open and under way.
- More trials run by University of NebraskaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 1:1 Randomized, cross-over design
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Song-young Park, PhD, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03514875
- Sponsor's protocol ID
- 0088-18-FB
- Status last verified
- Aug 2023
- First submitted
- 20 Apr 2018
- Last updated
- 15 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 24224133Luchsinger 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.
PubMed 16116114Green 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.
PubMed 21263128Green 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.
PubMed 24277765
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Mitochondrial-targeted Antioxidant on Carotid Artery Endothelial Function and Brain Blood Flow in Mild Cognitive Impairment (MCI) Patients
- ClinicalTrials.gov ID
- NCT03514875
- Acronym / sponsor ID
- 0088-18-FB
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: discontinued due to change in operating plans prior to study initiation and enrollment
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Study start
- 11 Nov 2019 (actual)
- Primary completion
- 18 Jul 2022 (actual)
- Study completion
- 18 Jul 2022 (actual)
- First posted
- 2 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- 1:1 Randomized, cross-over design
| Arm | Type | Receives |
|---|---|---|
| MitoQ-Placebo | Experimental | Dietary Supplement: MitoQ, Dietary Supplement: PlaceboSubjects 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. |
| Placebo-MitoQ | Experimental | Dietary Supplement: MitoQ, Dietary Supplement: PlaceboSubjects 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. |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MitoQMitoQ is a mitochondria-targeting antioxidant, which should improve NO bioavailability, and therefore vasodilation | Dietary supplement | MitoQ-Placebo, Placebo-MitoQ |
| PlaceboA placebo will be used in a double blinded, randomized, cross-over design | Dietary supplement | MitoQ-Placebo, Placebo-MitoQ |
Primary outcome
Carotid artery blood flow
Time frame: 2 Days
Blood flow in the carotid artery will be measured with ultrasound
4 secondary outcomes
Oxidative Stress
Time frame: 2 days
Cerebrovascular Oxygenation
Time frame: 2 Days
Brain Electrical Activity
Time frame: 2 Days
Endothelial Function
Time frame: 2 Days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2023.
- Background: PubMed 24224133Kelleher 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.
- Background: PubMed 16116114Luchsinger 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.
- Background: PubMed 21263128Green 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.
- Background: PubMed 24277765Green 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Song-young Park, PhD principal investigator
University of Nebraska
Questions about this trial
What is this clinical trial studying?
A study testing MitoQ in people with Alzheimer Disease, Early Onset and Mild Cognitive Impairment, run by University of Nebraska.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 15 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Carotid artery blood flow (time frame: 2 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03514875, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2023.