MitoQ Supplementation and Cardiovascular Function in Healthy Men and Women

Study Overview
=================
Brief Summary
-----------------
In this pilot study, the investigators will determine whether supplementation with a mitochondrial-targeted antioxidant (Mitoquinone (MitoQ)) improves mitochondrial function, left ventricular diastolic and vascular function.

Detailed Description
-----------------
Heart failure affects over 5 million American adults and the risk of heart failure increases with age. Diastolic function typically declines with age. Targeting age-related causal factors leading to the decline in diastolic function in both women and men is a major public health initiative. In this pilot study, the investigators will determine whether supplementation with a mitochondrial-targeted antioxidant (Mitoquinone (MitoQ)) improves mitochondrial function, left ventricular diastolic and vascular function in older adults. As an exploratory aim, the investigators will determine whether there are differences between men and women in response to this supplementation.

Official Title
-----------------
Mitochondrial Targeted Antioxidant Supplementation and Diastolic Function in Healthy Men and Women

Conditions
-----------------
Diastolic Dysfunction

Intervention / Treatment
-----------------
* Dietary Supplement: MITOQUINOL MESYLATE then placebo
* Dietary Supplement: Placebo, then MITOQUINOL MESYLATE


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 50 - 75 years of age sedentary-to-recreationally active (<3 days of vigorous exercise); nonsmokers; healthy, as determined by medical history, physical examination, standard blood chemistries. Exclusion Criteria: history of cancer history of cardiovascular disease unwilling or unable to take MitoQ supplement; taking antioxidant vitamins, corticosteroids, or anti-inflammatory medications (e.g., aspirin); taking sex hormone therapy presence of menses within last 1 year; taking any other medications (e.g., antihypertensives, lipid lowering medications) that would interact with MitoQ or impact CV function

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A: 'MITOQUINOL MESYLATE then placebo<br>'MITOQUINOL MESYLATE' administered twice daily for 4 weeks followed by a washout, then placebo capsule administered twice daily for 4 weeks. Capsules with active product contain 20 mg of 'MITOQUINOL MESYLATE'. | Dietary Supplement: MITOQUINOL MESYLATE then placebo<br>* MITOQUINOL MESYLATE then placebo: 'MITOQUINOL MESYLATE' administered twice daily for 4 weeks followed by a washout, then placebo capsule administered twice daily for 4 weeks. Capsules with active product contain 20 mg of 'MITOQUINOL MESYLATE'.<br>* Other names: MitoQ, Mitoquinol methanesulfonate;|
| Experimental: B: Placebo then 'MITOQUINOL MESYLATE'<br>Placebo capsule administered twice daily for 4 weeks followed by a washout period, then 'MITOQUINOL MESYLATE' administered twice daily for 4 weeks. Capsules with active product contain 20 mg of 'MITOQUINOL MESYLATE' | Dietary Supplement: Placebo, then MITOQUINOL MESYLATE<br>* 'Placebo, then MITOQUINOL MESYLATE' : Placebo administered twice daily for 4 weeks followed by a washout, then 'MITOQUINOL MESYLATE' capsule administered twice daily for 4 weeks. Capsules with active product contain 20 mg of 'MITOQUINOL MESYLATE'.<br>* Other names: MitoQ, Mitoquinol methanesulfonate;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in diastolic function | Echocardiographic measurements of LV function (and structure) will be assessed; primary outcomes include peak early (E) to late (A) mitral inflow velocity ratio and E to peak early (e') mitral annular velocity ratio. | Baseline and 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in arterial stiffness | Parameters of arterial stiffness will be measured using SphygmoCor XCEL (Atcor) system (pulse-wave velocity [PWV], pulse wave analyses [PWA]). | Baseline and 4 weeks | 
| Changes in brachial artery flow-mediated dilation | Brachial artery diameter and flow velocity will be acquired and analyzed using Vascular Analysis Tools 5.5.1 | Baseline and 4 weeks | 
| Changes in endothelial function | Measure parameters using digital peripheral arterial tonometry (Endo-PAT 2000) | Baseline and 4 weeks | 
| Changes in arterial vascular coupling | Measure ratio between arterial stiffness [Ea] and ventricular stiffness [ELv] estimated from echocardiographic measures. | Baseline and 4 weeks | 
| Changes in mitochondrial function | Measure parameters of mitochondrial respiration using high-resolution respirometry performed on permeabilized PBMCs (Oroboros Oxygraph O2k); perform venous endothelial cell mitochondrial protein analyses (Fusion, Fission proteins, SIRT1, mitoSox, MnSOD) and oxidative stress (nitrotyrosine, NADPHoxidase). | Baseline and 4 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
MitoQ