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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01684930
Recruitment Status : Completed
First Posted : September 13, 2012
Results First Posted : January 1, 2016
Last Update Posted : August 29, 2017
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Jason Allen, Ph.D., Duke University

Tracking Information
First Submitted Date  ICMJE September 11, 2012
First Posted Date  ICMJE September 13, 2012
Results First Submitted Date  ICMJE November 25, 2015
Results First Posted Date  ICMJE January 1, 2016
Last Update Posted Date August 29, 2017
Study Start Date  ICMJE June 2012
Actual Primary Completion Date November 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 25, 2015)
  • Change in Exercise Capacity: VO2peak (Maximal Oxygen Consumption) [ Time Frame: Baseline and 16 Weeks ]
    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.
  • Change In Time To Exhaustion [ Time Frame: Baseline and 16 weeks ]
    Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test with expired gas analysis, for determination of total time to exhaustion.
Original Primary Outcome Measures  ICMJE
 (submitted: September 12, 2012)
Change In Exercise Capacity [ Time Frame: 16 Weeks ]
Maximal cardiopulmonary exercise capacity will be assessed using a with a CPX test using a Gardner protocol (specifically designed for a PAD+IC population) with expired gas analysis, for determination of peak VO2,COT,and PWT. The COT will be used to determine the exercise prescription.
Change History Complete list of historical versions of study NCT01684930 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 26, 2017)
  • Change in Functional Ability [ Time Frame: Baseline and 16 Weeks ]
    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 Claudication Onset Time [ Time Frame: Baseline and 16 weeks ]
    Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test with expired gas analysis, for determination of claudication onset time.
  • Change In Vascular Function (BAFMD) [ Time Frame: Baseline and 16 weeks ]
    Vascular Function is measured as Brachial artery flow-mediated dilation (BAFMD). BAFMD is a measure of change in artery diameter after a stimulus .
  • Change in Angiogenesis [ Time Frame: Baseline and 16 weeks ]
    Gastrocnemious muscle biopsy will be performed to measure the number of capillaries per fibre as a marker of change in angiogenesis between groups
Original Secondary Outcome Measures  ICMJE
 (submitted: September 12, 2012)
  • Change in Functional Ability [ Time Frame: 16 Weeks ]
    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: 16 weeks ]
    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: 16 weeks ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Nitrites, Exercise, and Peripheral Arterial Disease
Official Title  ICMJE Increased Plasma Nitrite, Tissue Oxygenation and Functional Changes in PAD
Brief Summary 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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Peripheral Arterial Disease
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Beetroot Juice (Beet-It Stamina Shot) & Supervised Exercise Training
  • 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.
    Intervention: Other: Placebo Comparator Beverage (Beet-It Stamina Shot) & Exercise Training
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 17, 2014)
32
Original Estimated Enrollment  ICMJE
 (submitted: September 12, 2012)
28
Actual Study Completion Date  ICMJE November 2014
Actual Primary Completion Date November 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01684930
Other Study ID Numbers  ICMJE Pro00031918
1R21HL111972-01 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jason Allen, Ph.D., Duke University
Study Sponsor  ICMJE Duke University
Collaborators  ICMJE National Heart, Lung, and Blood Institute (NHLBI)
Investigators  ICMJE
Principal Investigator: Jason Allen, PhD Duke University
PRS Account Duke University
Verification Date August 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP