Back to resultsO2 Transport and Utilization in Health and Lung Disease
Primary Purpose
COPD, Tetrahydrobiopterin Deficiency, Oxidative Stress
Status
Unknown status
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Tetrahydrobiopterin
Placebo oral tablet
Sponsored by
About this trial
This is an interventional basic science trial for COPD focused on measuring BH4, Exercise, Mitochondria, Vascular function
Eligibility Criteria
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
Sites / Locations
- Institute of Applied Life Sciences
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
acute BH4/Tetrahydrobiopterin treatment
Placebo
Arm Description
Oral supplement, Pill, 10 mg/kg of body weight
Oral supplement, Pill, Placebo pill with inert excipient
Outcomes
Primary Outcome Measures
Mitochondrial function
PCr recovery kinetics
intracellular PO2
Myoglobin oxygenation
Secondary Outcome Measures
systemic blood markers of oxidative stress
blood markers
Peripheral Blood flow
Exercise Blood flow by Doppler Ultrasound
Full Information
NCT ID
NCT04014712
First Posted
July 3, 2019
Last Updated
July 8, 2019
Sponsor
University of Massachusetts, Amherst
1. Study Identification
Unique Protocol Identification Number
NCT04014712
Brief Title
O2 Transport and Utilization in Health and Lung Disease
Official Title
Role of Nitric Oxide Coupling in Muscle Dysfunction With COPD
Study Type
Interventional
2. Study Status
Record Verification Date
July 2019
Overall Recruitment Status
Unknown status
Study Start Date
August 2019 (Anticipated)
Primary Completion Date
August 2022 (Anticipated)
Study Completion Date
August 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Massachusetts, Amherst
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COPD, Tetrahydrobiopterin Deficiency, Oxidative Stress
Keywords
BH4, Exercise, Mitochondria, Vascular function
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
Participant
Allocation
Randomized
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
acute BH4/Tetrahydrobiopterin treatment
Arm Type
Experimental
Arm Description
Oral supplement, Pill, 10 mg/kg of body weight
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Oral supplement, Pill, Placebo pill with inert excipient
Intervention Type
Drug
Intervention Name(s)
Tetrahydrobiopterin
Intervention Description
Oral, Single dose
Intervention Type
Drug
Intervention Name(s)
Placebo oral tablet
Intervention Description
Single dose
Primary Outcome Measure Information:
Title
Mitochondrial function
Description
PCr recovery kinetics
Time Frame
4 hours
Title
intracellular PO2
Description
Myoglobin oxygenation
Time Frame
4 hours
Secondary Outcome Measure Information:
Title
systemic blood markers of oxidative stress
Description
blood markers
Time Frame
4 hours
Title
Peripheral Blood flow
Description
Exercise Blood flow by Doppler Ultrasound
Time Frame
4 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Facility Information:
Facility Name
Institute of Applied Life Sciences
City
Amherst
State/Province
Massachusetts
ZIP/Postal Code
01003
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gwenael Layec, PhD
Phone
413-345-2739
Email
glayec@umass.edu
First Name & Middle Initial & Last Name & Degree
Mary Emma Searles
Email
msearles@umass.edu
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Time Frame
6 months post-publication
IPD Sharing 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.
Learn more about this trial
O2 Transport and Utilization in Health and Lung Disease
We'll reach out to this number within 24 hrs