Effect of Neo40 on PAD

The Effects of an Oral Nitric Oxide Lozenge on Peripheral Artery Disease

Reduced nitric oxide (NO) availability is a hallmark of a number of cardiovascular diseases (CVD) including peripheral artery disease (PAD). The investigators will test the hypothesis that sub-chronic NEO40™ supplementation will improve vascular NO function and improve intermittent claudication in patients with PAD. Using a prospective, double blind, placebo controlled experimental design in 30 patients, graded treadmill tests will be performed at baseline and after 3 months after randomization, according to the Skinner-Gardner protocol. Initial claudication distance (ICD) and absolute claudication distance (ACD) will be recorded. Two consecutive treadmill tests will be performed within 1 week at baseline (before administration of study drug); and 2 test will be performed at 3 months. Functional status will also be assessed by the Walking Impairment Questionnaire and the Health Status Survey SF-36 questionnaire (SF-36). Vascular function will be assessed with the use of a Vendys® vascular reactivity (endothelial function) test (Endothelix Inc). Digital pulse amplitude will be assessed using sensor probes on the index finger during reactive hyperemia. Blood will be collected for measurement (by Neogenis) of plasma levels of nitrite and nitrate at baseline and at the completion of the study. Based on previously published trials using this NO technology, the investigators predict that the group receiving the active supplement will exhibit an improvement in claudication distance and all measures of vascular function after 3 months.

Study Overview

• Status: Unknown
• Conditions: Peripheral Artery Disease
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Neo40

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Persons of at least 45 years of age
• Persons with unilateral or bilateral PAD confirmed by a resting ankle-brachial index (ABI) <0.9
• Persons with stable intermittent claudication for the previous 3 months
• Persons with the ability to walk 1 to 12 minutes on a treadmill. The pre-randomization treadmill test is limited by exercise-induced leg pain, which is relieved by cessation of the test. Variability of maximum walking distances between 2 consecutive screening treadmill tests will be <10%.

Exclusion Criteria:

• Persons with ischemic rest pain, ulceration or gangrene
• Persons with history in the previous 3 months of acute coronary syndrome or revascularization involving the peripheral or coronary arteries
• Persons with major amputation
• Persons with malignancy within the previous 5 years (except for treated non-melanoma skin cancer)
• Persons with proliferative retinopathy
• Persons with uncontrolled hypertension
• Persons with active inflammatory, infectious, or autoimmune diseases.
• Persons taking taking phosphodiesterase inhibitors, organic nitrates and/or hydralazine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Neo40 Supplement; Utilizing intellectual property developed out of the University of Texas Health Science Center in Houston, Neo40 is a GMP certified, over the counter, all natural formulation that provides a system for generating NO in an endothelium-dependent and independent manner. The NEO40™ Daily™ product ingredients list and packaging was submitted to FDA Office of Compliance by Neogenis Labs, Inc. for use as a dietary supplement. It is made up of Beet root extract, hawthorne berry, Vitamin C, L-citrulline and sodium nitrite. The lozenges utilize natural product chemistry activated by the saliva to generate authentic NO gas in the oral cavity through the one-electron reduction of nitrite. This product's formulation was designed to be a quick dissolve that melts in the mouth within four to five minutes.	Dietary supplement: Neo40
Placebo Comparator: Placebo; A placebo product has been manufactured that looks, tastes and feels like the Neo40 active lozenge without the active ingredients	Dietary supplement: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skinner-Gardner treadmill protocol.	The primary end point is the change at 3 months in the absolute claudication distance. Distance will be measured in meters walked on treadmill	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endothelial function	Secondary objectives are to evaluate endothelial function. EndoPAT score of 1.67 and below correlates to endothelial dysfunction.	3 months

Collaborators and Investigators

• Sponsor: HumanN
• Collaborators: The Methodist Hospital Research Institute

Study record dates

Study Major Dates

• Study Start: October 1, 2016
• Primary Completion (Anticipated): October 1, 2017
• Study Completion (Anticipated): October 1, 2017

Study Registration Dates

• First Submitted: October 12, 2016
• First Submitted That Met QC Criteria: October 14, 2016
• First Posted (Estimate): October 17, 2016

Study Record Updates

• Last Update Posted (Estimate): October 17, 2016
• Last Update Submitted That Met QC Criteria: October 14, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: exercise tolerance; nitric oxide; Neo40 supplement,
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Vascular Diseases; Peripheral Arterial Disease
• Other Study ID Numbers: R41AT009171-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED