O2 Transport and Utilization in Health and Lung Disease

Phase 1

Withdrawn

• Conditions: COPD; Tetrahydrobiopterin Deficiency; Oxidative Stress
• Interventions: Drug: Placebo oral tablet; Drug: Tetrahydrobiopterin

• Registration Number: NCT04014712
• Lead Sponsor: University of Massachusetts, Amherst

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.

Study Timeline

• Study First Submitted: 2019-07-03
• Study First Submitted QC: 2019-07-08
• Study First Posted: 2019-07-10
• Study Start: 2021-04
• Primary Completion: 2022-08
• Study Completion: 2022-08
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-12
• Last Update Posted: 2023-12-19

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo oral tablet	Oral supplement, Pill, Placebo pill with inert excipient
acute BH4/Tetrahydrobiopterin treatment	Tetrahydrobiopterin	Oral supplement, Pill, 10 mg/kg of body weight

Primary Outcome Measures

Name	Time	Method
Mitochondrial function	4 hours	PCr recovery kinetics
intracellular PO2	4 hours	Myoglobin oxygenation

Secondary Outcome Measures

Name	Time	Method
systemic blood markers of oxidative stress	4 hours	blood markers
Peripheral Blood flow	4 hours	Exercise Blood flow by Doppler Ultrasound

Trial Locations

Locations (1)

Institute of Applied Life Sciences; 🇺🇸 Amherst, Massachusetts, United States