Nitrites, Exercise, and Peripheral Arterial Disease - Full Text View

Purpose

The hypothesis of this proposal is that in subjects with PAD, regular consumption of a high nitrate supplement which raises plasma nitrite, in conjunction with 12 weeks of supervised exercise training at the limb ischemic threshold (SET) will produce a greater clinical benefit (increases in COT and PWT) than placebo plus supervised exercise at the limb ischemic threshold (PET).

Condition	Intervention	Phase
Peripheral Arterial Disease	Drug: Beetroot Juice (Beet-It Stamina Shot) & Supervised Exercise Training Other: Placebo Comparator Beverage (Beet-It Stamina Shot) & Exercise Training	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Increased Plasma Nitrite, Tissue Oxygenation and Functional Changes in PAD

Resource links provided by NLM:

MedlinePlus related topics: Exercise and Physical Fitness Peripheral Arterial Disease Vascular Diseases

U.S. FDA Resources

Further study details as provided by Duke University:

Primary Outcome Measures:

Change In Exercise Capacity [ Time Frame: Baseline and 16 Weeks ] [ Designated as safety issue: No ]
Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test with expired gas analysis, for determination of peak oxygen consumption, claudication onset time and peak walking time.

Secondary Outcome Measures:

Change in Functional Ability [ Time Frame: Baseline and 16 Weeks ] [ Designated as safety issue: No ]
Six-Minute Walk test. This test simple and practical assessment of functional capacity. The test measures the distance that a patient can walk on a flat, hard surface in a period of 6 minutes. The test is self-paced and assesses the submaximal level of functional capacity. The subjects choose their own intensity and are allowed to stop and rest if necessary during the test.
Change In Vascular Function [ Time Frame: Baseline and 16 weeks ] [ Designated as safety issue: No ]
Ankle-brachial Index (ABI), Brachial artery flow-mediated dilation (BAFMD), calf blood flow (plethysmography), and arterial stiffness (pulse wave velocity and pulse wave reflection).
Change in Angiogenesis [ Time Frame: Baseline and 16 weeks ] [ Designated as safety issue: No ]
Gastrocnemius muscle biopsy will be performed to measure markers of angiogenesis including; capillaries per unit area and per muscle fiber, endothelial cells with surrounding pericytes, relative fraction of type I, IIa, IIb, and IId/x fibers. If differences exist we will look for changes in cell proliferation (PCNA) and apoptosis (TUNEL); (b) oxidative capacity including; mitochondria volume with citrate synthase activity. (c) mitochondrial volume and density; (d) mitochondrial oxygen efficiency (respiratory control ratio, the ratio of ATP phosphorylation rate per oxygen consumption rate (P/O ratio), and maximal rate of ATP production). These are measurements for potential mediation analyses and gaining insight into the relative effect sizes will inform mechanistic aims in a larger trial.

Estimated Enrollment:	28
Study Start Date:	June 2012
Estimated Study Completion Date:	June 2014
Estimated Primary Completion Date:	June 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: BR Juice (Beet-It Stamina Shot) and Exercise Training Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 & 2) and at the end of the trial (between Visits 3 & 4). It also allows for comparisons of the combination of beetroot juice and chronic training effects (between Visits 2 & 3) to when the subject has not consumed the beverage (Visits 1 & 4). All subjects will consume Beet-It Stamina Shot 3 hours prior to all beverage tolerance visits, Testing Visits 2 & 3 and for all supervised exercise training visits during the 12 week intervention.	Drug: Beetroot Juice (Beet-It Stamina Shot) & Supervised Exercise Training The beverage is high in inorganic nitrate and bottled and supplied by James White Drinks. This supplement will be used in conjunction with supervised exercise training. Other Name: James White Drinks
Placebo Comparator: BR Juice Placebo and Exercise Training Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot; Placebo) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 & 2) and at the end of the trial (between Visits 3 & 4). It also allows for comparisons of the combination of placebo beverage and chronic training effects (between Visits 2 & 3) to when the subject has not consumed the beverage (Visits 1 & 4). All subjects will consume Beet-It Stamina Shot (Placebo) 3 hours prior to all beverage tolerance visits, Testing Visits 2 & 3 and for all supervised exercise training visits during the 12 week intervention.	Other: Placebo Comparator Beverage (Beet-It Stamina Shot) & Exercise Training The beverage is identical in look and taste to Beet-It Stamina Shot but with active ingredient removed. It is also bottled and supplied by James White Drinks. This placebo supplement will be used in conjunction with supervised exercise training. Other Name: James White Drinks

Arms

Assigned Interventions

Experimental: BR Juice (Beet-It Stamina Shot) and Exercise Training

Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 & 2) and at the end of the trial (between Visits 3 & 4). It also allows for comparisons of the combination of beetroot juice and chronic training effects (between Visits 2 & 3) to when the subject has not consumed the beverage (Visits 1 & 4). All subjects will consume Beet-It Stamina Shot 3 hours prior to all beverage tolerance visits, Testing Visits 2 & 3 and for all supervised exercise training visits during the 12 week intervention.

Drug: Beetroot Juice (Beet-It Stamina Shot) & Supervised Exercise Training

The beverage is high in inorganic nitrate and bottled and supplied by James White Drinks. This supplement will be used in conjunction with supervised exercise training.

Other Name: James White Drinks

Placebo Comparator: BR Juice Placebo and Exercise Training

Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot; Placebo) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 & 2) and at the end of the trial (between Visits 3 & 4). It also allows for comparisons of the combination of placebo beverage and chronic training effects (between Visits 2 & 3) to when the subject has not consumed the beverage (Visits 1 & 4). All subjects will consume Beet-It Stamina Shot (Placebo) 3 hours prior to all beverage tolerance visits, Testing Visits 2 & 3 and for all supervised exercise training visits during the 12 week intervention.

Other: Placebo Comparator Beverage (Beet-It Stamina Shot) & Exercise Training

The beverage is identical in look and taste to Beet-It Stamina Shot but with active ingredient removed. It is also bottled and supplied by James White Drinks. This placebo supplement will be used in conjunction with supervised exercise training.

Other Name: James White Drinks

Eligibility

Ages Eligible for Study:	40 Years to 85 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Peripheral Arterial Disease (ABI of less than 0.9)
Intermittent Claudication for 3 or more months

Exclusion Criteria:

Individuals with known alcohol or drug abuse problems
Individuals who have suffered a heart attack or stroke, or have changes on a resting ECG, in the last 3 months
Those classified as American Heart Association Class D
Gangrene, impending limb loss or osteomyelitis
Lower extremity vascular surgery, angioplasty or lumbar sympathectomy within 3 months of enrollment
Severe peripheral neuropathy
Any condition other than PAD that limits walking
Chest pain during treadmill exercise which appears before the onset of claudication, or >3mm ST depression during exercise
Subjects taking nitrates or nitroglycerin products
Must not be taking protein pump inhibitor medications

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01684930

Contacts

Contact: Mitch D VanBruggen, M.A.	919-660-6638	mitch.vanbruggen@duke.edu
Contact: Katherine L Ham, M.S.	919-660-6793	katherine.ham@duke.edu

Locations

United States, North Carolina
Duke Center for Living; Wallace Clinic	Recruiting
Durham, North Carolina, United States, 27710
Contact: Jason D Allen, PhD 919-660-6764 j.d.allen@duke.edu
Principal Investigator: Jason D Allen, PhD

Sponsors and Collaborators

Duke University

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator:

Jason Allen, PhD

Duke University

More Information

Additional Information:

Frederick R. Cobb Non-Invasive Vascular Research Laboratory This link exits the ClinicalTrials.gov site

Duke Clinical Trials Listing This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Jason Allen, Ph.D., Assistant Professor Doctor of Physical Therapy Program & Division of Cardiovascular Medicine, Duke University
ClinicalTrials.gov Identifier:	NCT01684930 History of Changes
Other Study ID Numbers:	Pro00031918, 1R21HL111972-01
Study First Received:	September 11, 2012
Last Updated:	March 22, 2013
Health Authority:	United States: Institutional Review Board United States: Food and Drug Administration

Keywords provided by Duke University:

Cardiovascular Diseases
Vascular Diseases
Arterial Occlusive Diseases
Exercise
Functional Capacity

Additional relevant MeSH terms:

Peripheral Arterial Disease
Peripheral Vascular Diseases
Atherosclerosis
Arteriosclerosis

Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on May 16, 2013

Nitrites, Exercise, and Peripheral Arterial Disease (NO-PAD)