Nitrate Supplementation and Exercise Tolerance in Patients With Type 2 Diabetes

NCT02804932 | Completed Results DMC

• 1 other identifier: 201511802
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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).

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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

Study Arms (2)

Beetroot crystals (nitrate)

EXPERIMENTAL

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

Dietary Supplement: Super Beets

Placebo (beetroot powder, no nitrate)

PLACEBO COMPARATOR

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

Other: Super Beets Placebo

Interventions

Super Beets DIETARY_SUPPLEMENT

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

Also known as: Beetroot crystals

Beetroot crystals (nitrate)

Super Beets Placebo OTHER

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

Also known as: Beetroot crystals no nitrate

Placebo (beetroot powder, no nitrate)

Eligibility Criteria

• Age: 40 Years - 77 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Darren P Casey: lead
• American Diabetes Association: collaborator

Study Sites (1)

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Related Publications (2)

• Bock JM, Hanson BE, Miller KA, Seaberg NT, Ueda K, Feider AJ, Hanada S, Lira VA, Casey DP. Eight weeks of inorganic nitrate/nitrite supplementation improves aerobic exercise capacity and the gas exchange threshold in patients with type 2 diabetes. J Appl Physiol (1985). 2022 Dec 1;133(6):1407-1414. doi: 10.1152/japplphysiol.00478.2022. Epub 2022 Nov 3.

  PMID: 36326473 DERIVED

• 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.

  PMID: 35639721 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Limitations and Caveats

Final number of participants studied with muscle biopsies was smaller than the total number of subjects enrolled in the study. The lower number was influenced by: (i) subjects not consenting to the muscle biopsy procedure; or (ii) technical problems occurring in at least one of the testing visits (ex: not enough muscle tissue and/or extensive proportion of intramuscular fat obtained).

Results Point of Contact

• Title: Dr. Darren Casey
• Organization: University of Iowa

darren-casey@uiowa.edu

13193841009

Study Officials

• Darren P Casey, PhD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: June 14, 2016
• First Posted: June 17, 2016
• Study Start: August 15, 2016
• Primary Completion: December 20, 2019
• Study Completion: December 20, 2019
• Last Updated: May 28, 2024
• Results First Posted: May 28, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)