Actively Recruiting
The Interaction Between Inorganic Nitrate Supplementation and Metformin on Exercise Capacity, Vascular Function, and Insulin Sensitivity in Individuals With Pre-Diabetes
Led by University of Virginia · Updated on 2026-06-03
24
Participants Needed
1
Research Sites
4 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are studying whether short-term supplementation with inorganic nitrate, given as beetroot juice, can improve blood vessel health, insulin sensitivity, and exercise capacity in people with prediabetes. The study compares individuals currently taking metformin with those who have never taken it. The goal is to find non-drug options to help manage prediabetes and potentially prevent type 2 diabetes. Participants will receive either nitrate-rich beetroot juice or nitrate-depleted beetroot juice for 4 days. The nitrate-rich juice contains 6.45 mmol of nitrate twice daily for 3 days and a double dose 2 hours before a lab visit. After a minimum 7-day washout period, participants will switch to the other supplement in a randomized, double-blind crossover design. Two groups will be compared: those on metformin and those who are metformin-naive. During the study, participants will undergo tests of vascular function, including pulse wave analysis and flow-mediated dilation, skin microvascular assessments, and exercise tests measuring peak oxygen uptake and time to exhaustion. An oral glucose tolerance test will assess insulin sensitivity. Researchers will also analyze blood and oral microbiome samples and monitor exercise responses and tissue oxygenation. The study lasts at least 4 days per supplement period with assessments following each phase.
CONDITIONS
Brief Title
Interaction Between Inorganic Nitrate Supplementation and Metformin in Individuals With Prediabetes
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Individuals able to communicate with the investigator and provide written consent
- Confirmed prediabetes, aged 18 to 60 years, defined by 2-hour glucose 140-199 mg/dL or HbA1c 5.7-6.4% on two tests within 6 months
- Taking metformin with stable dose for at least a week or naive to metformin
- Sedentary lifestyle (less than 1 day per week of structured exercise)
- Able to exercise on a cycle ergometer without help
- Stable medication regimen for the last 6 months
- If female, has a normal menstrual cycle
You will not qualify if you...
- Estimated Glomerular filtration rate (GFR) 45 or less
- Body mass index 40 kg/m2 or higher
- HbA1c greater than 6.4%
- Smoked within the last 5 years
- Significant weight loss (~3 kg) in last 3 months or taking weight loss drugs
- Medical conditions preventing high-intensity exercise
- Currently on any hormone replacement therapy
- History of heart attack, stroke, or unstable disease other than prediabetes or obesity
- Taking certain medications including calcium channel blockers, statins, ACE inhibitors, angiotensin receptor blockers, nitrates, alpha- or beta-blockers, diuretics, proton pump inhibitors, PDE-5 inhibitors, or xanthine oxidase inhibitors
- Used oral antibiotics or antibacterial mouthwash in the last 4 weeks and unwilling to stop
- Oral cancer or severe oral disease
- Uncontrolled high blood pressure (>140/90)
- Had hysterectomy or oophorectomy
- Pregnant, nursing, children, prisoners, cognitively impaired, or non-English speakers
AI-Screening
AI-Powered Screening
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Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - 4 days per supplementation period with at least 7 days washout between periods
Participants will supplement with either nitrate-rich beetroot juice or nitrate-depleted placebo for 4 days, with a crossover after a 7-day washout period. Their vascular health, insulin sensitivity, and exercise capacity will be measured following each supplementation period.
2 supplementation periods with associated visits for measurements; visits occur post-supplementation
Trial Site Locations
Total: 1 location
1
University of Virginia
Charlottesville, Virginia, United States, 22903
Actively Recruiting
Research Team
M
Money Ghimire, M.S
How is the study designed?
Study Type
INTERVENTIONAL
Masking
QUADRUPLE
Allocation
RANDOMIZED
Model
CROSSOVER
Primary Purpose
OTHER
Number of Arms
4
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