O2 Transport and Utilization in Health and Lung Disease

Study Overview
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Brief Summary
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Skeletal muscle dysfunction is a frequent and clinically relevant systemic manifestation of Chronic Pulmonary Obstructive Disease (COPD), which is still poorly understood. Therefore, the focus of this study is on the role of a deficit in tetrahydrobiopterin and nitric oxide synthase uncoupling induced by chronic oxidative stress on metabolic and vascular abnormalities in skeletal muscle of patients suffering from COPD.

Detailed Description
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The purpose of this study is to assess the efficacy of supplementation with tetrahydrobiopterin (BH4) for improving vascular and muscle function in patients with COPD and healthy controls.

Official Title
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Role of Nitric Oxide Coupling in Muscle Dysfunction With COPD

Conditions
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COPD, Tetrahydrobiopterin Deficiency, Oxidative Stress

Intervention / Treatment
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* Drug: Tetrahydrobiopterin
* Drug: Placebo oral tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All subjects must be between the age of 18 and 85 years; For the COPD cohort, patients with a diagnosis of stable COPD (i.e., those not experiencing an acute exacerbation of symptoms) and spirometric evidence of airway obstruction (FEV1 <80% predicted, FEV/FVC<0.70); Ability to perform motor tests; Ability to provide informed consent Exclusion Criteria: uncontrolled hypertension; hyperlipidemia; recent exacerbation; Major cardiovascular event procedure (<3 months); Pregnancy known significant hepatic, renal disease, active substance abuse contraindication to MRI, claustrophobia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: acute BH4/Tetrahydrobiopterin treatment<br>Oral supplement, Pill, 10 mg/kg of body weight | Drug: Tetrahydrobiopterin<br>* Oral, Single dose<br>|
| Placebo Comparator: Placebo<br>Oral supplement, Pill, Placebo pill with inert excipient | Drug: Placebo oral tablet<br>* Single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mitochondrial function | PCr recovery kinetics | 4 hours | 
| intracellular PO2 | Myoglobin oxygenation | 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| systemic blood markers of oxidative stress | blood markers | 4 hours | 
| Peripheral Blood flow | Exercise Blood flow by Doppler Ultrasound | 4 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BH4, Exercise, Mitochondria, Vascular function