Impacts of Mitochondrial-targeted Antioxidant on Peripheral Artery Disease Patients
Paraules clau
Resum
Descripció
Previous studies reported that atherosclerotic lesions are distributed non-uniformly in the leg arteries, and the resulting impaired blood flow, and concomitant reduced oxygen delivery to skeletal muscle results in the pathophysiology of PAD. We have recently demonstrated that patients with PAD have higher levels of systemic and local skeletal muscle inflammation due to impaired oxygen transfer capacity of leg blood vessels, which causes hypoxic conditions, meaning lack of oxygen, in the leg skeletal muscle. Skeletal muscle mitochondrial dysfunction and elevated reactive oxygen species (ROS) represent key pathological processes linked to atherosclerosis-mediated hypoxic and metabolic stress in PAD patients. One potential defensive mechanism to these negative consequences of impaired oxygen transfer capacity-induced hypoxic stress may be having higher levels of antioxidant capacity. MitoQ, a derivative of CoQ10, is a commercial antioxidant that counteracts this oxidative stress within the mitochondria. High ROS levels have been positively correlated with reduced NO bioavailability, which limits the ability of the blood vessels to dilate, thereby increasing the occlusion that leads to claudication in PAD patients. MitoQ should reduce these ROS levels and increase vasodilatory function. However, the influence of MitoQ intake on leg blood flow, ROS production, claudication and leg function has not yet been investigated in this disease population. This research project may help us to understand the beneficial effects of higher mitochondrial specific antioxidant capacity on oxygen transfer capacity of leg blood vessels, mitochondria function, leg performance and leg pain in patients with PAD.
Dates
Darrera verificació: | 06/30/2020 |
Primer enviat: | 04/12/2018 |
Inscripció estimada enviada: | 04/12/2018 |
Publicat per primera vegada: | 04/23/2018 |
Última actualització enviada: | 07/06/2020 |
Publicació de l'última actualització: | 07/08/2020 |
Data d'inici de l'estudi real: | 09/04/2018 |
Data estimada de finalització primària: | 11/30/2020 |
Data estimada de finalització de l’estudi: | 01/31/2021 |
Condició o malaltia
Intervenció / tractament
Dietary Supplement: MitoQ
Fase
Grups de braços
Braç | Intervenció / tractament |
---|---|
Experimental: MitoQ-Placebo Subjects will be tested on two different days, first day will be baseline and MitoQ and second day will be Placebo. Testing will take place forty-minutes after MitoQ/placebo intake. There will be a 2-week washout between testing days. | |
Experimental: Placebo-MitoQ Subjects will be tested on two different days, first day will be baseline and Placebo and second day will be MitoQ. Testing will take place forty-minutes after placebo/MitoQ intake. There will be a 2-week washout between testing days. |
Criteris d'elegibilitat
Edats elegibles per estudiar | 50 Years Per a 50 Years |
Sexes elegibles per estudiar | All |
Accepta voluntaris saludables | Sí |
Criteris | Inclusion Criteria: 1. be able to give written, informed consent 2. demonstrate positive history of chronic claudication 3. have a history of exercise limiting claudication 4. have an ankle/brachial index < 0.90 at rest 5. have a stable blood pressure regimen, stable lipid regimen, stable diabetes regimen and risk factor control for 6 weeks. 6. be between 50-85 years old Exclusion Criteria: 1. rest pain or tissue loss due to PAD (Fontaine stage III and IV) 2. acute lower extremity ischemic event secondary to thromboembolic disease or acute trauma 3. walking capacity limited by conditions other than claudication including leg (joint/musculoskeletal, neurologic) and systemic (heart, lung disease) pathology |
Resultat
Mesures de resultats primaris
1. Endothelial Function [2 days]
Mesures de resultats secundaris
1. Walking Function [Maximum of 14 minutes on 2 separate days]
2. Oxidative Stress [2 days]
3. Skeletal Muscle Oxygenation [2 days]
4. Nitroglycerin-mediated dilation [2 days]