Trial Outcomes & Findings for Dietary Nitrate and Exercise to Augment Exercise Training Benefits in Subjects With DM+PAD (NCT NCT01785524)

NCT ID: NCT01785524

Last Updated: 2017-07-27

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 18 participants
• Primary outcome timeframe: Baseline & 16 Weeks
• Results posted on: 2017-07-27

Participant Flow

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.

Participant milestones

Measure	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. 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.	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. 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.
Overall Study STARTED	7	4
Overall Study COMPLETED	5	2
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Measure	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. 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.	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. 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.
Overall Study Withdrawal by Subject	2	2

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	BR Juice (Beet-It Stamina Shot) & Supervised Exercise Training n=7 Participants 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.	BR Juice Placebo and Exercise Training n=4 Participants 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 n=11 Participants Total of all reporting groups
Age, Continuous	70.1 years STANDARD_DEVIATION 4.7 • n=5 Participants	74.25 years STANDARD_DEVIATION 5.1 • n=7 Participants	71.63 years STANDARD_DEVIATION 5.04 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Measure	BR Juice (Beet-It Stamina Shot) & Supervised Exercise Training n=5 Participants 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.	BR Juice Placebo and Exercise Training n=2 Participants 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.
Change in Exercise Capacity - Maximal Oxygen Capacity (VO2peak)	0.85 ml/kg/min Standard Deviation 0.57	-0.15 ml/kg/min Standard Deviation 1.13

PRIMARY outcome

Timeframe: Baseline & 16 Weeks

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

Outcome measures

Measure	BR Juice (Beet-It Stamina Shot) & Supervised Exercise Training n=5 Participants 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.	BR Juice Placebo and Exercise Training n=2 Participants 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.
Change in Exercise Capacity - Time to Exhaustion (TTE)	196.25 seconds Standard Deviation 201	247.5 seconds Standard Deviation 249.61

PRIMARY outcome

Timeframe: Baseline & 16 Weeks

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

Outcome measures

Measure	BR Juice (Beet-It Stamina Shot) & Supervised Exercise Training n=5 Participants 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.	BR Juice Placebo and Exercise Training n=2 Participants 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.
Change in Exercise Capacity - Claudication Onset Time (COT)	189 seconds Standard Deviation 238.17	77.5 seconds Standard Deviation 36.06

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	BR Juice (Beet-It Stamina Shot) & Supervised Exercise Training n=5 Participants 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.	BR Juice Placebo and Exercise Training n=2 Participants 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.
Change in Functional Ability	131 feet Standard Deviation 288.08	47.5 feet Standard Deviation 137.89

SECONDARY outcome

Timeframe: Baseline and 16 weeks

Population: participants who underwent the gastrocnemius muscle biopsies

Gastrocnemious muscle biopsy will be performed to measure the number of capillaries per fibre as a marker of change in angiogenesis between groups.

Outcome measures

Measure	BR Juice (Beet-It Stamina Shot) & Supervised Exercise Training n=2 Participants 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.	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. 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.
Change in Angiogenesis	2 ratio of capillaries to muscle fibres Standard Deviation 0.22	—

SECONDARY outcome

Timeframe: Baseline and 16 weeks

Population: participants who completed study

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

Outcome measures

Measure	BR Juice (Beet-It Stamina Shot) & Supervised Exercise Training n=5 Participants 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.	BR Juice Placebo and Exercise Training n=2 Participants 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.
Change In Vascular Function	1.83 change % dilation	-3.56 change % dilation

Adverse Events

BR Juice (Beet-It Stamina Shot) & Supervised Exercise Training

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

BR Juice Placebo and Exercise Training

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Jason D. Allen, PhD

Victoria University

Phone: 61 3 9919 4264

Email: jason.allen@vu.edu.au

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place