Type 2 DiabetesNCT02804932
Nitrate Supplementation and Exercise Tolerance in Patients With Type 2 Diabetes
A study testing Super Beets in people with Type 2 Diabetes, run by Darren P Casey at 1 site in United States.
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). Read more about this study
- Who is it for?
- Ages 40 to 77 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- Super Beets
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 54 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Aug 2016to 20 Dec 2019
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 77 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
- 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
Who cannot join
- 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
Show all 26Show fewer
- 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
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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).
Read the 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.
- Conditions
- Type 2 Diabetes
- Being tested
- Super Beets, Super Beets Placebo
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Super BeetsDietary supplement
Also called Beetroot crystals
Nitrate rich beetroot powder (10g/day) for 8 weeks
Super Beets PlaceboOther
Also called Beetroot crystals no nitrate
Nitrate deficient beetroot powder (10g/day) for 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| Beetroot crystals (nitrate) | Experimental | Participants will receive a nitrate rich beetroot powder (10g/day) for 8 weeks. Receives: Dietary Supplement: Super Beets |
| Placebo (beetroot powder, no nitrate) | Placebo comparator | Participants will receive a beetroot powder placebo (no nitrate) for 8 weeks. Receives: Other: Super Beets Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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°.
Measured: Pre and post 8 weeks of dietary nitrate supplementation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2016 (estimated)
- Study start15 Aug 2016
- Primary completion20 Dec 2019
- Study completion20 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Darren P Casey
- Sponsor type
- University, hospital or other
- Collaborators
- American Diabetes Association
- Responsible party
- Sponsor-investigator, Darren P Casey, University of Iowa
- Investigators
- Darren P Casey, PhD, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02804932
- Sponsor's protocol ID
- 201511802
- Status last verified
- Dec 2023
- First submitted
- 14 Jun 2016
- Last updated
- 28 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 36326473Bock 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.
PubMed 35639721
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nitrate Supplementation and Exercise Tolerance in Patients With Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT02804932
- Acronym / sponsor ID
- 201511802
- Conditions
- Type 2 Diabetes
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Darren P CaseyUniversity, hospital or other
- Collaborators
- American Diabetes Association
- Study start
- 15 Aug 2016 (actual)
- Primary completion
- 20 Dec 2019 (actual)
- Study completion
- 20 Dec 2019 (actual)
- First posted
- 17 Jun 2016 (estimated)
- Results
- Posted 28 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Beetroot crystals (nitrate) | Experimental | Dietary Supplement: Super BeetsParticipants will receive a nitrate rich beetroot powder (10g/day) for 8 weeks. |
| Placebo (beetroot powder, no nitrate) | Placebo comparator | Other: Super Beets PlaceboParticipants will receive a beetroot powder placebo (no nitrate) for 8 weeks. |
Who may qualify
- Ages
- 40 to 77 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
- 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
Key exclusion criteria (26 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Super BeetsAlso: Beetroot crystalsNitrate rich beetroot powder (10g/day) for 8 weeks | Dietary supplement | Beetroot crystals (nitrate) |
| Super Beets PlaceboAlso: Beetroot crystals no nitrateNitrate deficient beetroot powder (10g/day) for 8 weeks | Other | Placebo (beetroot powder, no nitrate) |
Primary outcome
Maximal Exercise Capacity (VO2max)
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 maximal aerobic capacity (VO2max) and exercise efficiency.
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.
Change in Skeletal Muscle Mitochondrial Function
Time frame: Pre and post 8 weeks of dietary nitrate supplementation
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°.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36326473Bock 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.
- Derived from this study: PubMed 35639721Bock 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Darren P Casey, PhD principal investigator
University of Iowa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Super Beets in people with Type 2 Diabetes, run by Darren P Casey at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximal Exercise Capacity (VO2max) (time frame: Pre and post 8 weeks of dietary nitrate supplementation). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02804932, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2024.