ClinicalTrials.gov
ClinicalTrials.gov Menu

Nitrate Supplementation and Exercise Tolerance in Patients With Type 2 Diabetes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02804932
Recruitment Status : Recruiting
First Posted : June 17, 2016
Last Update Posted : March 29, 2018
Sponsor:
Collaborator:
American Diabetes Association
Information provided by (Responsible Party):
Darren P Casey, University of Iowa

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).

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Dietary Supplement: Super Beets Other: Super Beets Placebo Not Applicable

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 65 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: Nitrate Supplementation and Exercise Tolerance in Patients With Type 2 Diabetes
Study Start Date : June 2016
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : January 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Beetroot crystals (nitrate)
Participants will receive a nitrate rich beetroot powder (10g/day) for 8 weeks.
Dietary Supplement: Super Beets
Nitrate rich beetroot powder (10g/day) for 8 weeks
Other Name: Beetroot crystals

Placebo Comparator: Placebo (beetroot powder, no nitrate)
Participants will receive a beetroot powder placebo (no nitrate) for 8 weeks.
Other: Super Beets Placebo
Nitrate deficient beetroot powder (10g/day) for 8 weeks
Other Name: Beetroot crystals no nitrate




Primary Outcome Measures :
  1. Change in exercise capacity [ Time Frame: Pre and post 8 weeks of dietary nitrate supplementation ]
    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.

  2. Change in skeletal muscle perfusion during exercise [ Time Frame: Pre and post 8 weeks of dietary nitrate supplementation ]
    Forearm blood flow will be determined using Doppler ultrasound during rhythmic forearm exercise

  3. Change in skeletal muscle mitochondrial function [ Time Frame: Pre and post 8 weeks of dietary nitrate supplementation ]
    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°.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   40 Years to 77 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02804932


Contacts
Contact: Darren P Casey, PhD 319-384-1009 darren-casey@uiowa.edu

Locations
United States, Iowa
University of Iowa Recruiting
Iowa City, Iowa, United States, 52242
Sponsors and Collaborators
Darren P Casey
American Diabetes Association
Investigators
Principal Investigator: Darren P Casey, PhD University of Iowa

Responsible Party: Darren P Casey, Assistant Professor, University of Iowa
ClinicalTrials.gov Identifier: NCT02804932     History of Changes
Other Study ID Numbers: 201511802
First Posted: June 17, 2016    Key Record Dates
Last Update Posted: March 29, 2018
Last Verified: March 2018

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Methamphetamine
Central Nervous System Stimulants
Physiological Effects of Drugs
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic Agents
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Dopamine Uptake Inhibitors