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

• Sponsor: Duke University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01785524
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 18
• Location: 1
• Arms: 2
• Duration (Months): 21
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Peripheral Arterial Disease; 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 Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, 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)
• Study Start Date: Feb 1, 2013
• Actual Primary Completion Date: Nov 1, 2014
• Actual Study Completion Date: Nov 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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 Names: James White Drinks

Outcome Measures

Primary Outcome Measures

1. Change in Exercise Capacity - Maximal Oxygen Capacity (VO2peak) [Baseline & 16 Weeks]

   Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test with expired gas analysis, for determination of peak oxygen consumption

2. Change in Exercise Capacity - Time to Exhaustion (TTE) [Baseline & 16 Weeks]

   Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test for determination of Time to Exhaustion (TTE)

3. Change in Exercise Capacity - Claudication Onset Time (COT) [Baseline & 16 Weeks]

   Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test for determination of Claudication Onset Time (COT)

Secondary Outcome Measures

1. Change in Functional Ability [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.

2. Change in Angiogenesis [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.

3. Change In Vascular Function [Baseline and 16 weeks]

   Vascular Function will be measured as the Brachial artery flow-mediated dilation (BAFMD)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Duke Diet & Fitness Center	Durham	North Carolina	United States	27710

Sponsors and Collaborators

• Duke University
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Jason D Allen, PhD, Duke University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Frederick R. Cobb Non-Invasive Vascular Research Laboratory
• Duke Clinical Trials Listing

Publications

None provided.

• Responsible Party: Jason Allen, Ph.D., Assistant Professor Doctor of Physical Therapy Program & Division of Cardiovascular Medicine, Duke University
• ClinicalTrials.gov Identifier: NCT01785524
• Other Study ID Numbers: Pro00039608; 5R21HL113717-02
• First Posted: Feb 7, 2013
• Last Update Posted: Jul 27, 2017
• Last Verified: Jul 1, 2017

• Keywords provided by Jason Allen, Ph.D., Assistant Professor Doctor of Physical Therapy Program & Division of Cardiovascular Medicine, Duke University: Cardiovascular Diseases; Vascular Diseases; Arterial Occlusive Diseases; Diabetes; Exercise; Functional Capacity
• Additional relevant MeSH terms: Peripheral Arterial Disease; Peripheral Vascular Diseases; Diabetes Mellitus, Type 2

Study Results

Participant Flow

Recruitment Details	6,852 patients in Duke Cardiology and Vascular Surgery Clinics were screened, 392 potential study candidates were identified, and 18 subjects were enrolled from March 2013 through January 2014. Of the 18 subjects, 11 were randomized and 7 completed all study testing.

Arm/Group Title	BR Juice (Beet-It Stamina Shot) & Supervised Exercise Training	BR Juice Placebo and Exercise Training
Arm/Group Description	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. 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.	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. 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.
Period Title: Overall Study
STARTED	7	4
COMPLETED	5	2
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	BR Juice (Beet-It Stamina Shot) & Supervised Exercise Training	BR Juice Placebo and Exercise Training	Total
Arm/Group Description	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. 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.	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. 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.	Total of all reporting groups
Overall Participants	7	4	11
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70.1 (4.7)	74.25 (5.1)	71.63 (5.04)
Sex: Female, Male (Count of Participants)
Female	1 14.3%	1 25%	2 18.2%
Male	6 85.7%	3 75%	9 81.8%

Outcome Measures

1. Primary Outcome

Title	Change in Exercise Capacity - Maximal Oxygen Capacity (VO2peak)
Description	Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test with expired gas analysis, for determination of peak oxygen consumption
Time Frame	Baseline & 16 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BR Juice (Beet-It Stamina Shot) & Supervised Exercise Training	BR Juice Placebo and Exercise Training
Arm/Group Description	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. 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.	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. 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.
Measure Participants	5	2
Mean (Standard Deviation) [ml/kg/min]	0.85 (0.57)	-0.15 (1.13)

2. Primary Outcome

Title	Change in Exercise Capacity - Time to Exhaustion (TTE)
Description	Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test for determination of Time to Exhaustion (TTE)
Time Frame	Baseline & 16 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BR Juice (Beet-It Stamina Shot) & Supervised Exercise Training	BR Juice Placebo and Exercise Training
Arm/Group Description	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. 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.	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. 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.
Measure Participants	5	2
Mean (Standard Deviation) [seconds]	196.25 (201)	247.5 (249.61)

3. Primary Outcome

Title	Change in Exercise Capacity - Claudication Onset Time (COT)
Description	Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test for determination of Claudication Onset Time (COT)
Time Frame	Baseline & 16 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BR Juice (Beet-It Stamina Shot) & Supervised Exercise Training	BR Juice Placebo and Exercise Training
Arm/Group Description	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. 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.	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. 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.
Measure Participants	5	2
Mean (Standard Deviation) [seconds]	189 (238.17)	77.5 (36.06)

4. Secondary Outcome

Title	Change in Functional Ability
Description	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.
Time Frame	Baseline and 16 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BR Juice (Beet-It Stamina Shot) & Supervised Exercise Training	BR Juice Placebo and Exercise Training
Arm/Group Description	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. 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.	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. 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.
Measure Participants	5	2
Mean (Standard Deviation) [feet]	131 (288.08)	47.5 (137.89)

5. Secondary Outcome

Title	Change in Angiogenesis
Description	Gastrocnemious muscle biopsy will be performed to measure the number of capillaries per fibre as a marker of change in angiogenesis between groups.
Time Frame	Baseline and 16 weeks

Outcome Measure Data

Analysis Population Description

participants who underwent the gastrocnemius muscle biopsies

Arm/Group Title	BR Juice (Beet-It Stamina Shot) & Supervised Exercise Training	BR Juice Placebo and Exercise Training
Arm/Group Description	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. 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.	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. 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.
Measure Participants	2	0
Mean (Standard Deviation) [ratio of capillaries to muscle fibres]	2 (0.22)

6. Secondary Outcome

Title	Change In Vascular Function
Description	Vascular Function will be measured as the Brachial artery flow-mediated dilation (BAFMD)
Time Frame	Baseline and 16 weeks

Outcome Measure Data

Analysis Population Description

participants who completed study

Arm/Group Title	BR Juice (Beet-It Stamina Shot) & Supervised Exercise Training	BR Juice Placebo and Exercise Training
Arm/Group Description	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. 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.	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. 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.
Measure Participants	5	2
Number [change % dilation]	1.83	-3.56

Adverse Events

Arm/Group Title	BR Juice (Beet-It Stamina Shot) & Supervised Exercise Training		BR Juice Placebo and Exercise Training
Arm/Group Description	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. 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.		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. 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.
All Cause Mortality
	BR Juice (Beet-It Stamina Shot) & Supervised Exercise Training		BR Juice Placebo and Exercise Training
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	BR Juice (Beet-It Stamina Shot) & Supervised Exercise Training		BR Juice Placebo and Exercise Training
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	BR Juice (Beet-It Stamina Shot) & Supervised Exercise Training		BR Juice Placebo and Exercise Training
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/4 (0%)

Limitations/Caveats

The largest limitation to the study was the evolving knowledge on conversion rates of oral inorganic nitrate to nitrite. We found a good deal of unexpected inter and intra-subject variation in conversion rates.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.