O2 Transport and Utilization in Health and Lung Disease

Role of Nitric Oxide Coupling in Muscle Dysfunction With COPD

Status

Withdrawn

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04014712

Enrollment

Registered

2019-07-10

Start date

2021-04-30

Completion date

2022-08-31

Last updated

2023-12-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

COPD, Tetrahydrobiopterin Deficiency, Oxidative Stress

Keywords

BH4, Exercise, Mitochondria, Vascular function

Brief summary

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

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.

Interventions

DRUGTetrahydrobiopterin

Oral, Single dose

DRUGPlacebo oral tablet

Single dose

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

BASIC_SCIENCE

Masking

SINGLE (Subject)

Eligibility

Sex/Gender

ALL

Age

18 Years to 85 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
Mitochondrial function	4 hours	PCr recovery kinetics
intracellular PO2	4 hours	Myoglobin oxygenation

Secondary

Measure	Time frame	Description
systemic blood markers of oxidative stress	4 hours	blood markers
Peripheral Blood flow	4 hours	Exercise Blood flow by Doppler Ultrasound

Countries

United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026