Trial Outcomes & Findings for Nitrites, Exercise, and Peripheral Arterial Disease (NCT NCT01684930)

NCT ID: NCT01684930

Last Updated: 2017-08-29

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 32 participants
• Primary outcome timeframe: Baseline and 16 Weeks
• Results posted on: 2017-08-29

Participant Flow

10,817 patients were screened, 898 potential study candidates were identified, and 32 subjects signed consent and were enrolled from June 2012 through July 2014. Of the 32 subjects who signed consent, 5 subjects were screen failures and 1 withdrew consent. 26 subjects were randomized and 22 subjects completed all study testing.

Participant milestones

Measure	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. 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.	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	12	14
Overall Study COMPLETED	9	13
Overall Study NOT COMPLETED	3	1

Reasons for withdrawal

Measure	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. 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.	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	3	1

Baseline Characteristics

Nitrites, Exercise, and Peripheral Arterial Disease

Baseline characteristics by cohort

Measure	BR Juice (Beet-It Stamina Shot) and Exercise Training n=12 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) \& 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.	BR Juice Placebo and Exercise Training n=14 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=26 Participants Total of all reporting groups
Age, Continuous	63.25 years STANDARD_DEVIATION 8.9 • n=5 Participants	71.85 years STANDARD_DEVIATION 7.9 • n=7 Participants	67.88 years STANDARD_DEVIATION 9.3 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 16 Weeks

Population: All participants who completed study.

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.

Outcome measures

Measure	BR Juice (Beet-It Stamina Shot) and Exercise Training n=9 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) \& 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.	BR Juice Placebo and Exercise Training n=13 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: VO2peak (Maximal Oxygen Consumption)	1.48 ml/kg/min Standard Deviation 2.69	0.23 ml/kg/min Standard Deviation 2.21

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	BR Juice (Beet-It Stamina Shot) and Exercise Training n=9 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) \& 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.	BR Juice Placebo and Exercise Training n=13 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 Time To Exhaustion	289.56 seconds Standard Deviation 175.44	254.92 seconds Standard Deviation 210.48

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) and Exercise Training n=9 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) \& 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.	BR Juice Placebo and Exercise Training n=13 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	172.89 feet Standard Deviation 166.05	95 feet Standard Deviation 173.7

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	BR Juice (Beet-It Stamina Shot) and Exercise Training n=9 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) \& 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.	BR Juice Placebo and Exercise Training n=13 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 Claudication Onset Time	199.22 seconds Standard Deviation 143.47	48.58 seconds Standard Deviation 198.75

SECONDARY outcome

Timeframe: Baseline and 16 weeks

Population: participants with analyzable data

Vascular Function is measured as Brachial artery flow-mediated dilation (BAFMD). BAFMD is a measure of change in artery diameter after a stimulus .

Outcome measures

Measure	BR Juice (Beet-It Stamina Shot) and Exercise Training n=4 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) \& 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.	BR Juice Placebo and Exercise Training n=6 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 (BAFMD)	-1.14 % dilation Standard Deviation 3.02	-0.19 % dilation Standard Deviation 1.80

SECONDARY outcome

Timeframe: Baseline and 16 weeks

Population: Participants who had a gastrocnemius muscle biopsy with enough tissue to analyze.

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) and 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) \& 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.	BR Juice Placebo and Exercise Training n=8 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 Angiogenesis	0.38 capillaries per fibrer Standard Deviation 0.54	0.26 capillaries per fibrer Standard Deviation 0.51

Adverse Events

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

Serious events: 0 serious events

Other events: 1 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

Measure	BR Juice (Beet-It Stamina Shot) and Exercise Training n=12 participants at risk 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) \& 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.	BR Juice Placebo and Exercise Training n=14 participants at risk 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.
Cardiac disorders hypotensive episode with exercise	8.3% 1/12	0.00% 0/14

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