Nitrate Supplementation and Exercise Tolerance in Patients With Type 2 Diabetes

Type 2 Diabetes Clinical Trial

Official title:

Nitrate Supplementation and Exercise Tolerance in Patients With Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02804932
• Other study ID #: 201511802
• Status: Completed
• Phase: N/A
• Start date: August 15, 2016
• Est. completion date: December 20, 2019

Study information

• Verified date: December 2023
• Source: University of Iowa
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: December 20, 2019
• Est. primary completion date: December 20, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 77 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Dietary Supplement:
• Super Beets
Nitrate rich beetroot powder (10g/day) for 8 weeks

Other:
• Super Beets Placebo
Nitrate deficient beetroot powder (10g/day) for 8 weeks

Locations

Country	Name	City	State
United States	University of Iowa	Iowa City	Iowa

Sponsors (2)

Lead Sponsor	Collaborator
Darren P Casey	American Diabetes Association

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximal Exercise Capacity (VO2max)	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 maximal aerobic capacity (VO2max) and exercise efficiency.	Pre and post 8 weeks of dietary nitrate supplementation
Primary	Change in Skeletal Muscle Perfusion During Exercise	Forearm blood flow will be determined using Doppler ultrasound during rhythmic forearm exercise.	Pre and post 8 weeks of dietary nitrate supplementation
Primary	Change in Skeletal Muscle Mitochondrial Function	Muscle biopsies were obtained from the vastus lateralis using a Bergstrom needle with suction under local anesthesia, which will yield ~200-250mg of tissue. Mitochondrial function was assessed as follows: Fiber bundles were chemically permeabilized with saponin and mitochondrial respiration was analyzed by in situ high-resolution respirometry at 37°.	Pre and post 8 weeks of dietary nitrate supplementation