O2 Transport and Utilization in Health and Lung Disease

NCT04014712 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 2018-4815
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

COPD; Tetrahydrobiopterin Deficiency; Oxidative Stress

Keywords

BH4; Exercise; Mitochondria; Vascular function

Outcome Measures

Primary Outcomes (2)

• Mitochondrial function

  PCr recovery kinetics

  4 hours

• intracellular PO2

  Myoglobin oxygenation

  4 hours

Secondary Outcomes (2)

• systemic blood markers of oxidative stress

  4 hours

• Peripheral Blood flow

  4 hours

Study Arms (2)

acute BH4/Tetrahydrobiopterin treatment

EXPERIMENTAL

Oral supplement, Pill, 10 mg/kg of body weight

Drug: Tetrahydrobiopterin

Placebo

PLACEBO COMPARATOR

Oral supplement, Pill, Placebo pill with inert excipient

Drug: Placebo oral tablet

Interventions

Tetrahydrobiopterin DRUG

Oral, Single dose

acute BH4/Tetrahydrobiopterin treatment

Placebo oral tablet DRUG

Single dose

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• uncontrolled hypertension;
• hyperlipidemia;
• recent exacerbation;
• Major cardiovascular event procedure (\<3 months);
• Pregnancy
• known significant hepatic, renal disease, active substance abuse
• contraindication to MRI, claustrophobia

Sponsors & Collaborators

• University of Massachusetts, Amherst: lead

Study Sites (1)

Institute of Applied Life Sciences

Amherst, Massachusetts, 01003, United States

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Phenylketonurias; Motor Activity

Interventions

sapropterin

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Behavior

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2019
• First Posted: July 10, 2019
• Study Start: April 1, 2021
• Primary Completion: August 1, 2022
• Study Completion: August 1, 2022
• Last Updated: December 19, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: 6 months post-publication
• Access Criteria: Within 6 months after the data have been published, and upon written request, a limited, de-identified, anonymized dataset will be created pursuant to the Data use Agreement.

Locations

US (1)