Long Term Nitric Oxide Bioavailability on Vascular Health in Chronic Obstructive Pulmonary Disease

NCT02774226 | Completed Phase 2 Results DMC

• 1 other identifier: COPD-LT
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic obstructive pulmonary disease (COPD) affects up to 14 million people and is among the top five leading causes of death worldwide. Although COPD is a disease of the lungs, recent evidence indicates that COPD is associated with multiple systemic consequences including vascular endothelial dysfunction. Recently, it has been suggested that more patients with COPD die from cardiovascular disease and coronary heart disease than of direct pulmonary complications. Examination of the mechanisms that contribute to a reduction nitric oxide (NO) bioavailability resulting in vascular endothelial dysfunction in patients with COPD are important as endothelial dysfunction has been indicated to be an independent predictor of future atherosclerotic cardiovascular disease and events.

Conditions

Chronic Obstructive Pulmonary Disease (COPD)

Keywords

Flow-Mediated Dilation; Kuvan; Antioxidant; FEV1

Outcome Measures

Primary Outcomes (1)

• Change in Flow Mediated Dilation

  Brachial artery FMD induced by reactive hyperemia assessed vascular endothelial function at baseline and 12 weeks after treatment.

  Change from Baseline and 12 weeks

Secondary Outcomes (3)

• Change in PWV (Pulse Wave Velocity)

  Change from Baseline and 12 weeks

• FEV1 %Predicted

  Change from Baseline and 12 weeks

• Percent of ACH to Heat Max

  Change from Baseline and 12 weeks

Study Arms (2)

Tetrahydrobiopterin (BH4)

EXPERIMENTAL

Blood samples, flow-mediated dilation, arterial stiffness, lung function, and microvascular function will be performed at baseline and 12 weeks following 5mg/kg of Kuvan® or sapropterin dihydrochloride which is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4), taken once a day.

Drug: Tetrahydrobiopterin (BH4)

Antioxidant Cocktail

EXPERIMENTAL

Blood samples, flow-mediated dilation, arterial stiffness, lung function, and microvascular function will be performed at baseline and 12 weeks following an anti-oxidant cocktail (vitamin C 1000 mg, vitamin E 400 IU, and alpha lipoic acid 600 mg) taken once a day.

Dietary Supplement: Antioxidant Cocktail

Interventions

Tetrahydrobiopterin (BH4) DRUG

12 week intervention

Also known as: Kuvan (Sapropterin Dihydrochloride)

Tetrahydrobiopterin (BH4)

Antioxidant Cocktail DIETARY_SUPPLEMENT

12 week intervention

Also known as: Vitamin C, Vitamin E, Alpha Lipoic Acid

Antioxidant Cocktail

Eligibility Criteria

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

You may qualify if:

• patients with medically diagnosed COPD
• apparently healthy controls

You may not qualify if:

• FEV1/FVC \>0.7 (normal lung function in patients only)
• Clinical diagnosis of heart disease or diabetes
• Vasoactive medications (i.e. nitrates, beta-blockers, Viagra etc.)
• uncontrolled high blood pressure
• high blood pressure in your lungs
• thyroid problems
• Fluid in the lungs
• Sleep apnea
• Anemia
• Raynaud's Phenomenon
• GI bleeding
• Gangrene of the digits
• History of low platelets or coagulopathies
• Phenylketonuria (PKU)
• Any allergy to Kuvan

Sponsors & Collaborators

• Augusta University: lead

Study Sites (1)

Georgia Prevention Institute

Augusta, Georgia, 30912, United States

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

sapropterin; Ascorbic Acid; Vitamin E; Thioctic Acid

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thiophenes; Sulfur Compounds; Coenzymes; Enzymes and Coenzymes; Fatty Acids; Lipids

Results Point of Contact

• Title: Dr. Ryan Harris
• Organization: Augusta University

ryharris@augusta.edu

706-721-5483

Study Officials

• Ryan Harris, Ph.D

  Augusta University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 11, 2016
• First Posted: May 17, 2016
• Study Start: September 1, 2015
• Primary Completion: July 30, 2018
• Study Completion: July 30, 2018
• Last Updated: February 23, 2021
• Results First Posted: February 23, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will share

Locations

US (1)