Interaction Between Inorganic Nitrate Supplementation and Metformin in Individuals With Prediabetes
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-60
SponsorUniversity of Virginia
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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)
Disqualifiers
Estimated Glomerular filtration rate (GFR) ≤ 45
Body mass index ≥ 40 Kg/m2
HbA1c > 6.4%
Smokers within the last 5 years
Trial design
Design model
Crossover
Treatments tested in this trial
Dietary Supplement: Inorganic Nitrate (Beetroot juice)
Dietary supplementParticipants 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)
Dietary supplementParticipants 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).
Treatment groups
24 Participants
are divided into 4 treatment groupsGroup A: Active Comparator (Naive to metformin)Experimental treatment 1 intervention
Group B: Placebo Comparator (Naive to metformin)Placebo comparator 1 intervention
Group C: Active Comparator (Taking metformin)Experimental treatment 1 intervention
Group D: Placebo Comparator (Taking metformin)Placebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
Vascular Endothelial Function (Pulse wave analysis and velocity [PWA/V])
PWA/V- These measures will be calculated using the SphygmoCor XCEL system (AtCor Medical). This system will provide arterial stiffness, central, and peripheral pressure waveforms.
Time frame
3 days following either active NO3 or placebo without nitrate (following 7-day washout).2
Vascular Endothelial Function (Flow-Mediated Dilation [FMD])
FMD- Participants will be placed in a supine position with their left forearm slightly extended and supinated, and their legs straight. The arteries will be imaged using a high-resolution 7.5 MHz linear array transducer at rest, during 5 minutes of forearm occlusion via cuff inflation, and continuously for 3 minutes post-occlusion. An EKG trigger will be used to capture images during the end-diastole of the cardiac cycle.
Time frame
3 days following either active NO3 or placebo without nitrate (following 7-day washout).3
Skin microvascular function using post-occlusive reactive hyperemia (PORH)
Skin microvascular function will be measured using Moor Instruments' FLPI-2 laser speckle imaging system. PORH will also be measured during the FMD measurement. Baseline measures will be captured, and the cuff will be inflated for 5 minutes, with the post-occlusion reactive period being measured. The laser positioned above the forearm skin will measure skin blood flow at all these time points.
Time frame
3 days following either active NO3 or placebo without nitrate (following 7-day washout)4
Skin microvascular function: Change in Skin Microvascular Dilation in Response to Local Thermal Heating
Skin microvascular function will be measured using Moor Instruments' FLPI-2 laser speckle imaging system. For LTH, \~2 mL of diH2O will be placed on a small disc on the forearm. The solution will be slowly heated to 44 °C. This will allow us to measure the endothelial function of the microcirculation in the skin.
Time frame
3 days following either active NO3 or placebo without nitrate (following 7-day washout).Secondary outcomes
1
Oral Microbiome
In order to assess abundance and classification of nitrate-reducing bacteria, a sample of the oral microbiome will be obtained. The dorsal surface of the tongue will be swabbed using a 6" HydraFlock Sterile Large Flock Swab for 60 seconds (Puritan Medical Products, USA). Additionally, an unstimulated saliva sample (\~5ml) will be collected through an unstimulated drool technique. Both swab and saliva samples will be sequenced to analyze bacteria present in the oral microbiome following supplement/placebo.
Time frame
4 days following either active NO3 or placebo without nitrate (following 7-day washout).2
Biomarker Analyses: Concentration of Inflammatory markers in fasting blood plasma
The investigators plan to assess various markers of inflammation. A fasting blood sample will be collected to measure markers of inflammation.
Time frame
Sample collected 4 days post active NO3 juice/placebo and will be analyzed post study completion.3
Biomarker Analyses: Concentration of Oxidative stress markers in fasting blood plasma
The investigators plan to assess various markers of oxidative stress. A fasting blood sample will be collected to measure markers of oxidative stress.
Time frame
Sample collected 4 days post active NO3 juice/placebo and will be analyzed post study completion.Sponsors and contacts
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Source ClinicalTrials.gov