Recruiting

Inorganic Nitrate with Metformin

Sponsor:

University of Virginia

Code:

NCT07131384

Conditions

Males

Females

Sedentary

Metformin

Prediabetes

Eligibility Criteria

Sex: All

Age: 18 - 60

Healthy Volunteers: Not accepted

Interventions

Dietary Supplement: Inorganic Nitrate (Beetroot juice)

Dietary supplement: Placebo (Nitrate-depleted beetroot juice)

Study Details

Brief summary:

This study is examining whether short-term supplementation with inorganic nitrate, in the form of beetroot juice, can enhance blood vessel health, insulin sensitivity, and exercise capacity in individuals with prediabetes. We will be comparing the responses in individuals who are taking metformin to those who are naive to metformin. The results from this study may help identify non-pharmacological interventions in prediabetes.

Conditions

Males

Females

Sedentary

Metformin

Prediabetes

Study ID

NCT07131384

Start date

Jan 1, 2026

Status verified date

Jun, 2026

Completion date

Jun 30, 2027

Anticipated

Primary completion date

Jun 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 60

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Individuals who can communicate meaningfully with the investigator and can provide written consent.
  • Confirmed prediabetic individuals (ages 18-60 years old) (2-hour glucose of 140-199 mg/dL following OGTT test or HbA1c between 5.7-6.4% tested on two occasions within 6 months).
  • Taking metformin (stable dose for at least a week) or naïve to metformin
  • Sedentary (<1 day/week of structured exercise)
  • Be able to perform exercise on a cycle ergometer without assistance
  • Stable medication regimen for the last 6 months
  • If female, have a normal menstrual cycle

Exclusion Criteria:

  • Estimated Glomerular filtration rate (GFR) ≤ 45
  • Body mass index ≥ 40 Kg/m2
  • HbA1c > 6.4%
  • Smokers within the last 5 years
  • Has experienced significant weight loss \~3 kg in the last three months or is taking any weight loss drugs
  • Current medical condition that prohibits exercising at high intensities
  • Currently on hormone replacement of any kind
  • History of myocardial infarction, cerebrovascular event, acute or unstable disease other than pre-diabetes or obesity
  • Currently taking any of the following medications (calcium channel blockers, statins, ACE or renin inhibitors, angiotensin receptor blockers, organic nitrates (e.g., nitroglycerine) or recent regular use of inorganic nitrates, alpha- or beta-blockers, diuretics, proton pump inhibitors, PDE-5 inhibitors (e.g.,: Cialis, Viagra), or xanthine oxidase inhibitors (e.g.,: Allopurinol))
  • Oral antibiotic use within the previous four weeks, including over-the-counter antibacterial mouthwash or a mouthwash containing chlorhexidine and unwilling to discontinue use
  • Oral cancer/severe oral disease
  • Uncontrolled hypertension (>140/90)
  • Had hysterectomy or oophorectomy
  • Fetuses, neonates, children, prisoners, cognitively impaired, non-English speaking participants

Study Design

Enrollment

24 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Other

Interventions and Outcome Measures

Arms

experimental: Active Comparator (Naive to metformin)

Participants will supplement with nitrate-rich beetroot juice (BRJ) for 4 days: 6.45 mmol of NO3 in the morning and 6.45 mmol in the evening for 3 days, and 12.9 mmol 2 hours before the lab visit. Supplement order based on randomization and crossover will happen after a minimum of a 7-day washout period.

placebo comparator: Placebo Comparator (Naive to metformin)

Participants will supplement with nitrate-depleted beetroot juice (BRJ) for 4 days: 6.45 mmol of NO3 in the morning and 6.45 mmol in the evening for 3 days, and 12.9 mmol 2 hours before the lab visit. Supplement order based on randomization and crossover will happen after a minimum of a 7-day washout period.

experimental: Active Comparator (Taking metformin)

Participants will supplement with nitrate-rich beetroot juice (BRJ) for 4 days: 6.45 mmol of NO3 in the morning and 6.45 mmol in the evening for 3 days, and 12.9 mmol 2 hours before the lab visit. Supplement order based on randomization and crossover will happen after a minimum of a 7-day washout period.

placebo comparator: Placebo Comparator (Taking metformin)

Participants will supplement with nitrate-depleted beetroot juice (BRJ) for 4 days: 6.45 mmol of NO3 in the morning and 6.45 mmol in the evening for 3 days, and 12.9 mmol 2 hours before the lab visit. Supplement order based on randomization and crossover will happen after a minimum of a 7-day washout period.

Interventions

Dietary Supplement: Inorganic Nitrate (Beetroot juice)

Participants will be supplemented with inorganic nitrate in the form of beetroot juice for 4 days (12.9 mmol of NO3/day), and their vascular health, insulin sensitivity, and exercise capacity will be measured post-supplementation. This is a randomized crossover design with 2 parallel groups (Group 1: Currently taking metformin, Group 2: Naive to metformin).

Dietary supplement: Placebo (Nitrate-depleted beetroot juice)

Participants will be supplemented with nitrate-depleted beetroot juice for 4 days (<0.01 mmol NO3/day), and their vascular health, insulin sensitivity, and exercise capacity will be measured post-supplementation. This is a randomized crossover design with 2 parallel groups (Group 1: Currently taking metformin, Group 2: Naive to metformin).

Primary outcome measure

  • Vascular Endothelial Function (Pulse wave analysis and velocity [PWA/V]) [ Time Frame: 3 days following either active NO3 or placebo without nitrate (following 7-day washout). ]
  • Vascular Endothelial Function (Flow-Mediated Dilation [FMD]) [ Time Frame: 3 days following either active NO3 or placebo without nitrate (following 7-day washout). ]
  • Skin microvascular function using post-occlusive reactive hyperemia (PORH) [ Time Frame: 3 days following either active NO3 or placebo without nitrate (following 7-day washout) ]
  • Skin microvascular function: Change in Skin Microvascular Dilation in Response to Local Thermal Heating [ Time Frame: 3 days following either active NO3 or placebo without nitrate (following 7-day washout). ]
  • Skin microvascular function: Change in microvascular dilation in response to acetylcholine (ACh) [ Time Frame: 3 days following either active NO3 or placebo without nitrate (following 7-day washout) ]
  • Oral Glucose Tolerance Test (OGTT) [ Time Frame: 3 days following either active NO3 or placebo without nitrate (following 7-day washout). ]
  • Plasma Nitrate/Nitrite [ Time Frame: 4 days following either active NO3 or placebo without nitrate (following 7-day washout). ]
  • Cardiorespiratory fitness [ Time Frame: 4 days following either active NO3 or placebo without nitrate (following 7 day washout). ]
  • Exercise time trial to exhaustion (TTE) [ Time Frame: 4 days following either active NO3 or placebo without nitrate (following 7 day washout). ]
  • Tissue oxygenation during exercise (near-infrared spectropscopy [NIRS] [ Time Frame: 4 days following either active NO3 or placebo without nitrate (following 7-day washout). ]
  • Oral nitrate reducing capacity (ONRC) [ Time Frame: 4 days following either active NO3 or placebo without nitrate (following 7-day washout). ]

Central Contacts and Locations

Central contacts

Money Ghimire, M.S

4342438677eta8xd@uvahealth.org

Locations

University of Virginia

Recruiting

Charlottesville, Virginia, United States, 22903

Contacts

434-243-8677eta8xd@uvahealth.org

More Information

Sponsor

University of Virginia

Last update posted

Jun 3, 2026

Last verified

Jun, 2026

Keywords

  • Prediabetic Individuals
  • Exercise Capacity
  • Vascular health
  • Inorganic nitrate
  • Insulin Sensitivity

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Virginia on 2026-06-03.