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

NCT01785524 | Completed Phase 2 Results

• 2 other identifiers: Pro000396085R21HL113717-02
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Peripheral Arterial Disease; Type II Diabetes Mellitus

Keywords

Cardiovascular Diseases; Vascular Diseases; Arterial Occlusive Diseases; Diabetes; Exercise; Functional Capacity

Outcome Measures

Primary Outcomes (3)

• Change in Exercise Capacity - Maximal Oxygen Capacity (VO2peak)

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

  Baseline & 16 Weeks

• Change in Exercise Capacity - Time to Exhaustion (TTE)

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

  Baseline & 16 Weeks

• Change in Exercise Capacity - Claudication Onset Time (COT)

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

  Baseline & 16 Weeks

Secondary Outcomes (3)

• Change in Functional Ability

  Baseline and 16 Weeks

• Change in Angiogenesis

  Baseline and 16 weeks

• Change In Vascular Function

  Baseline and 16 weeks

Study Arms (2)

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

EXPERIMENTAL

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

BR Juice Placebo and Exercise Training

PLACEBO COMPARATOR

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

Interventions

Beetroot Juice (Beet-It Stamina Shot) and Exercise Training DRUG

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.

Also known as: James White Drinks

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

Placebo Comparator Beverage (Beet-It Stamina Shot) & Exercise Training OTHER

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.

Also known as: James White Drinks

BR Juice Placebo and Exercise Training

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Peripheral Arterial Disease (ABI of less than 0.9)
• Diagnosed Type II Diabetes
• Intermittent Claudication for 3 or more months

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Duke Diet & Fitness Center

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• Woessner M, VanBruggen MD, Pieper CF, Sloane R, Kraus WE, Gow AJ, Allen JD. Beet the Best? Circ Res. 2018 Aug 31;123(6):654-659. doi: 10.1161/CIRCRESAHA.118.313131.

  PMID: 29976553 DERIVED

Related Links

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

MeSH Terms

Conditions

Peripheral Arterial Disease; Diabetes Mellitus, Type 2; Cardiovascular Diseases; Vascular Diseases; Arterial Occlusive Diseases; Diabetes Mellitus; Motor Activity

Interventions

Exercise

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Peripheral Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Behavior

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Limitations and 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.

Results Point of Contact

• Title: Jason D. Allen, PhD
• Organization: Victoria University

jason.allen@vu.edu.au

61 3 9919 4264

Study Officials

• Jason D Allen, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor Doctor of Physical Therapy Program & Division of Cardiovascular Medicine

Study Record Dates

• First Submitted: February 5, 2013
• First Posted: February 7, 2013
• Study Start: February 1, 2013
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: July 27, 2017
• Results First Posted: January 5, 2016

Record last verified: 2017-07

Locations

US (1)