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Nitrate Supplementation and Exercise Tolerance in Patients With Type 2 Diabetes

Primary Purpose

Type 2 Diabetes

Status

Recruiting

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Super Beets

Super Beets Placebo

About this trial

This is an interventional basic science trial for Type 2 Diabetes

Eligibility Criteria

40 Years - 77 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

For 50 patients with documented Type 2 diabetes

Inclusion Criteria:

Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures.
Age is > or = 40 and < or = 77 years of age
Documented Type 2 diabetes

Exclusion Criteria:

diagnosis of type 2 diabetes < 3 years prior to enrollment
HbA1c <6.0% or >10.0%
body mass index > 42 kg/m2
incident cardiovascular events in the last year (heart attack, stroke)
symptomatic coronary artery disease and/or heart failure
uncontrolled hypertension
hypotension (resting systolic BP < 90 mmHg)
renal impairment with creatinine clearance (eGFR) of <50 ml/min
smoking or history of smoking within past one year
use of medication which contain nitrates
use of anti-coagulant drugs
use of anti-platelet drugs
participation in research studies in which medications or interventions are given which would potentially alter subject responses in the current study

For 15 age- and weight-matched nondiabetic control subjects

Inclusion Criteria:

Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures.
Age is > or = 40 and < or = 77 years of age

Exclusion Criteria:

Diagnosis of diabetes (Type 1 or Type 2)
body mass index > 42 kg/m2
incident cardiovascular events in the last year (heart attack, stroke)
symptomatic coronary artery disease and/or heart failure
uncontrolled hypertension
hypotension (resting systolic BP < 90 mmHg)
renal impairment with creatinine clearance (eGFR) of <50 ml/min
smoking or history of smoking within past one year
use of medication which contain nitrates
use of anti-coagulant drugs
use of anti-platelet drugs
participation in research studies in which medications or interventions are given which would potentially alter subject responses in the current study

Sites / Locations

University of IowaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Beetroot crystals (nitrate)

Placebo (beetroot powder, no nitrate)

Arm Description

Participants will receive a nitrate rich beetroot powder (10g/day) for 8 weeks.

Participants will receive a beetroot powder placebo (no nitrate) for 8 weeks.

Outcomes

Primary Outcome Measures

Change in exercise capacity

A 12-lead ECG, symptom limited cardiopulmonary exercise testing with gas exchange measurements will be performed on a cycle ergometer using a ramp protocol to determine peak aerobic capacity (VO2peak) and exercise efficiency.

Change in skeletal muscle perfusion during exercise

Forearm blood flow will be determined using Doppler ultrasound during rhythmic forearm exercise

Change in skeletal muscle mitochondrial function

Muscle biopsies will be obtained from the vastus lateralis using a Bergstrom needle with suction under local anesthesia, which will yield ~200-250mg of tissue. Mitochondrial function will be assessed as follows: Fiber bundles will be chemically permeabilized with saponin and mitochondrial respiration will be analyzed by in situ high-resolution respirometry at 37°.

Secondary Outcome Measures

Full Information

NCT ID

NCT02804932

First Posted

June 14, 2016

Last Updated

December 13, 2021

Sponsor

Darren P Casey

Collaborators

American Diabetes Association

1. Study Identification

Unique Protocol Identification Number

NCT02804932

Brief Title

Nitrate Supplementation and Exercise Tolerance in Patients With Type 2 Diabetes

Official Title

Nitrate Supplementation and Exercise Tolerance in Patients With Type 2 Diabetes

Study Type

Interventional

2. Study Status

Record Verification Date

December 2021

Overall Recruitment Status

Recruiting

Study Start Date

June 2016 (undefined)

Primary Completion Date

December 2022 (Anticipated)

Study Completion Date

December 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Darren P Casey

Collaborators

American Diabetes Association

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to use a randomized, double-blind, placebo controlled study design to comprehensively investigate the impact of 8-weeks of dietary nitrate supplementation on skeletal muscle blood flow, mitochondrial function, and exercise capacity in patients with type 2 diabetes (T2D).

Detailed Description

Patients with type 2 diabetes (T2D) demonstrate a reduced exercise capacity, a powerful predictor of cardiovascular mortality, which may be due to reductions in skeletal muscle perfusion and mitochondrial dysfunction. Nitric oxide (NO) is a key molecule involved in in the regulation of blood flow to contracting muscles, as well as a critical mediator in mitochondrial respiration. However, there appears to be a decreased enzymatic synthesis of NO and an overall reduction of bioavailable NO in patients with T2D, which likely contributes to the reduced exercise capacity and tolerance. Accumulating evidence suggests that exogenous nitrate supplementation is an effective option for increasing NO bioavailability in vivo. The purpose of the proposal is to use a randomized, double-blind, placebo controlled study design to comprehensively investigate the impact of 8-weeks of dietary nitrate supplementation on skeletal muscle blood flow, mitochondrial function, and exercise capacity in patients with T2D. The central hypothesis is that increasing NO bioavailability via dietary nitrate supplementation in patients with T2D will lead to improved oxygen delivery and utilization during exercise. To address this hypothesis a highly mechanistic and translational experimental strategy will be used to explore whether increased NO bioavailability via dietary nitrate supplementation improves skeletal muscle perfusion during exercise (Aim 1), enhances mitochondrial biogenesis and function (Aim 2), and improves exercise capacity and efficiency (Aim 3). Collectively, these studies will provide important mechanistic insight into the therapeutic potential of dietary nitrate supplementation for improving skeletal muscle blood flow, mitochondrial function and exercise capacity in patients with T2D.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 2 Diabetes

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

65 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Beetroot crystals (nitrate)

Arm Type

Experimental

Arm Description

Participants will receive a nitrate rich beetroot powder (10g/day) for 8 weeks.

Arm Title

Placebo (beetroot powder, no nitrate)

Arm Type

Placebo Comparator

Arm Description

Participants will receive a beetroot powder placebo (no nitrate) for 8 weeks.

Intervention Type

Dietary Supplement

Intervention Name(s)

Super Beets

Other Intervention Name(s)

Beetroot crystals

Intervention Description

Nitrate rich beetroot powder (10g/day) for 8 weeks

Intervention Type

Other

Intervention Name(s)

Super Beets Placebo

Other Intervention Name(s)

Beetroot crystals no nitrate

Intervention Description

Nitrate deficient beetroot powder (10g/day) for 8 weeks

Primary Outcome Measure Information:

Title

Change in exercise capacity

Description

Time Frame

Pre and post 8 weeks of dietary nitrate supplementation

Title

Change in skeletal muscle perfusion during exercise

Description

Forearm blood flow will be determined using Doppler ultrasound during rhythmic forearm exercise

Time Frame

Pre and post 8 weeks of dietary nitrate supplementation

Title

Change in skeletal muscle mitochondrial function

Description

Time Frame

Pre and post 8 weeks of dietary nitrate supplementation

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Maximum Age & Unit of Time

77 Years

Accepts Healthy Volunteers

Eligibility Criteria

For 50 patients with documented Type 2 diabetes Inclusion Criteria: Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures. Age is > or = 40 and < or = 77 years of age Documented Type 2 diabetes Exclusion Criteria: diagnosis of type 2 diabetes < 3 years prior to enrollment HbA1c <6.0% or >10.0% body mass index > 42 kg/m2 incident cardiovascular events in the last year (heart attack, stroke) symptomatic coronary artery disease and/or heart failure uncontrolled hypertension hypotension (resting systolic BP < 90 mmHg) renal impairment with creatinine clearance (eGFR) of <50 ml/min smoking or history of smoking within past one year use of medication which contain nitrates use of anti-coagulant drugs use of anti-platelet drugs participation in research studies in which medications or interventions are given which would potentially alter subject responses in the current study For 15 age- and weight-matched nondiabetic control subjects Inclusion Criteria: Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures. Age is > or = 40 and < or = 77 years of age Exclusion Criteria: Diagnosis of diabetes (Type 1 or Type 2) body mass index > 42 kg/m2 incident cardiovascular events in the last year (heart attack, stroke) symptomatic coronary artery disease and/or heart failure uncontrolled hypertension hypotension (resting systolic BP < 90 mmHg) renal impairment with creatinine clearance (eGFR) of <50 ml/min smoking or history of smoking within past one year use of medication which contain nitrates use of anti-coagulant drugs use of anti-platelet drugs participation in research studies in which medications or interventions are given which would potentially alter subject responses in the current study

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Darren P Casey, PhD

Phone

319-384-1009

darren-casey@uiowa.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Darren P Casey, PhD

Organizational Affiliation

University of Iowa

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Iowa

City

Iowa City

State/Province

Iowa

ZIP/Postal Code

52242

Country

United States

Individual Site Status

Recruiting

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

35639721

Citation

Bock JM, Hughes WE, Ueda K, Feider AJ, Hanada S, Casey DP. Dietary Inorganic Nitrate/Nitrite Supplementation Reduces Central and Peripheral Blood Pressure in Patients With Type 2 Diabetes Mellitus. Am J Hypertens. 2022 Sep 1;35(9):803-809. doi: 10.1093/ajh/hpac068.

Results Reference

derived

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Nitrate Supplementation and Exercise Tolerance in Patients With Type 2 Diabetes

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