Dietary Nitrate and Exercise to Augment Exercise Training Benefits in Subjects With DM+PAD

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Duke University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jason Allen, Ph.D., Duke University
ClinicalTrials.gov Identifier:
NCT01785524
First received: February 5, 2013
Last updated: March 3, 2014
Last verified: March 2014
  Purpose

The hypothesis of this proposal is that in subjects with Type II diabetes mellitus (T2D) and peripheral arterial disease (PAD) with intermittent claudication (IC), 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 claudication onset time [COT] and peak walking time [PWT] relative to a group with the same exercise training but supplemented with placebo .This study is essentially exploratory in nature and designed to provide us with information to adequately develop power and execute a larger study. We have previously seen benefits from nitrate supplementation on function in PAD.


Condition Intervention Phase
Peripheral Arterial Disease and Type II Diabetes Mellitus
Drug: Beetroot Juice (Beet-It Stamina Shot) and 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: Dietary Nitrate to Augment Exercise Training Benefits in Subjects With Type II Diabetes (DM) and Peripheral Arterial Disease (PAD)

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Change in Exercise Capacity [ Time Frame: Baseline & 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: February 2013
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BR Juice (Beet-It Stamina Shot) & Supervised 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) and 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)
  • Diagnosed Type II Diabetes
  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01785524

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   
Sponsors and Collaborators
Duke University
Investigators
Principal Investigator: Jason D Allen, PhD Duke University
  More Information

Additional Information:
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: NCT01785524     History of Changes
Other Study ID Numbers: Pro00039608
Study First Received: February 5, 2013
Last Updated: March 3, 2014
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
Diabetes
Exercise
Functional Capacity

Additional relevant MeSH terms:
Peripheral Arterial Disease
Peripheral Vascular Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Diabetes Mellitus
Diabetes Mellitus, Type 2
Atherosclerosis
Arteriosclerosis

ClinicalTrials.gov processed this record on July 29, 2014