Vascular Aging
Conditions
Keywords
endothelial function, arterial stiffness, flow-mediated dilation, pulse wave velocity, sodium nitrite, aging, vascular diseases
Brief summary
The proposed research will determine the effectiveness of nitrite, a naturally occurring compound in the body, for improving the health and function of arteries in middle-aged and older adults. The study also will provide insight into how sodium nitrite therapy improves artery health by determining the physiological mechanisms (biological reasons) involved. Overall, the proposed research will provide important new scientific evidence on the effectiveness of sodium nitrite for decreasing the risk of developing cardiovascular diseases with aging.
Detailed description
The improvement in blood vessel function and stiffness will be determined over a 10 week period. Subjects will be randomly assigned to either placebo (0 mg/day), low dose (80 mg/day) or high dose (160 mg/day) sodium nitrite. Main outcome measures will be performed at baseline and week 10.
Interventions
DRUGPlacebo
Sugar pill manufactured to mimic sodium nitrite capsules
DRUGSodium Nitrite
80 mg/d or 160 mg/d
Sponsors
TheraVasc Inc.
University of Colorado, Boulder
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 79 Years
Healthy volunteers
Yes
Inclusion criteria
* 50-79 years of age * Ability to provide informed consent * Score greater than 22 on the mini mental state exam * Blood pressure greater than 100/60 mmHg for past 3 months
Exclusion criteria
* Are taking any of the following medications/drugs: hormone replacement therapy, anti-hypertensives, nitrates, nervous system depressants, allopurinol, phosphodiesterase-5 inhibitors, blood thinners * Are currently sick/have chronic clinical diseases such as kidney disease, diabetes, or unstable cardiovascular disease * Are hypersensitive to nitrates or nitrites * Have glucose-6-phosphate dehydrogenase deficiency * Have blood methemoglobin greater than 2% * Have a BMI greater than 40 kg/m\^2 * Have a baseline FMD of greater than 6% * Have not been post-menopausal for at least 1 year * Perform regular vigorous aerobic/endurance exercise
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline and Week 10 Flow-Mediated Dilation | Baseline (Week 0), Week 10 | Brachial artery flow mediated dilation (FMD) is assessed prior to entering the study. If subjects pass the inclusion requirements, FMD is analyzed at baseline and week 10. Flow-Mediated Dilation is calculated as the percent change in artery diameter in response to 5 minutes of cuff occlusion at Baseline and Week 10 timepoints; i.e. (Peak Diameter-Baseline Diameter)/Baseline Diameter x 100. |
Secondary
| Measure | Time frame |
|---|---|
| Baseline and Week 10 Plasma Nitrite Concentrations | Baseline (Week 0), Week 10 |
| Baseline and Week 10 Aortic Pulse Wave Velocity | Baseline (Week 0), Week 10 |
Countries
United States
Participant flow
Recruitment details
Healthy men and women ages 50-79 years free of overt cardiovascular or chronic diseases.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo: Sugar pill manufactured to mimic sodium nitrite capsules | 11 |
| Sodium Nitrite 80 mg/d 80 mg/day (40 mg in morning; 40 mg in evening) oral capsules for 10 weeks
Sodium Nitrite: 80 mg/d or 160 mg/d | 10 |
| Sodium Nitrite 160 mg/d 160 mg/day (80 mg in morning; 80 mg in evening) oral capsules for 10 weeks
Sodium Nitrite: 80 mg/d or 160 mg/d | 12 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Sodium Nitrite 80 mg/d | Sodium Nitrite 160 mg/d | Total |
|---|---|---|---|---|
| Age, Continuous | 62 years STANDARD_DEVIATION 8 | 60 years STANDARD_DEVIATION 6 | 64 years STANDARD_DEVIATION 6 | 62 years STANDARD_DEVIATION 7 |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 6 Participants | 16 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 6 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 11 | 4 / 10 | 4 / 12 |
| serious Total, serious adverse events | 0 / 11 | 0 / 10 | 0 / 12 |
Outcome results
Primary
Baseline and Week 10 Flow-Mediated Dilation
Brachial artery flow mediated dilation (FMD) is assessed prior to entering the study. If subjects pass the inclusion requirements, FMD is analyzed at baseline and week 10. Flow-Mediated Dilation is calculated as the percent change in artery diameter in response to 5 minutes of cuff occlusion at Baseline and Week 10 timepoints; i.e. (Peak Diameter-Baseline Diameter)/Baseline Diameter x 100.
Time frame: Baseline (Week 0), Week 10
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Baseline and Week 10 Flow-Mediated Dilation | Baseline | 3.120 %Change | Standard Error 0.528 |
| Placebo | Baseline and Week 10 Flow-Mediated Dilation | Week 10 | 3.740 %Change | Standard Error 0.509 |
| Sodium Nitrite 80 mg/d | Baseline and Week 10 Flow-Mediated Dilation | Baseline | 4.307 %Change | Standard Error 0.501 |
| Sodium Nitrite 80 mg/d | Baseline and Week 10 Flow-Mediated Dilation | Week 10 | 6.833 %Change | Standard Error 0.785 |
| Sodium Nitrite 160 mg/d | Baseline and Week 10 Flow-Mediated Dilation | Baseline | 3.118 %Change | Standard Error 0.483 |
| Sodium Nitrite 160 mg/d | Baseline and Week 10 Flow-Mediated Dilation | Week 10 | 4.609 %Change | Standard Error 0.72 |
Secondary
Baseline and Week 10 Aortic Pulse Wave Velocity
Time frame: Baseline (Week 0), Week 10
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Baseline and Week 10 Aortic Pulse Wave Velocity | Baseline | 782 cm/sec | Standard Error 35 |
| Placebo | Baseline and Week 10 Aortic Pulse Wave Velocity | Week 10 | 774 cm/sec | Standard Error 36 |
| Sodium Nitrite 80 mg/d | Baseline and Week 10 Aortic Pulse Wave Velocity | Baseline | 780 cm/sec | Standard Error 55 |
| Sodium Nitrite 80 mg/d | Baseline and Week 10 Aortic Pulse Wave Velocity | Week 10 | 845 cm/sec | Standard Error 75 |
| Sodium Nitrite 160 mg/d | Baseline and Week 10 Aortic Pulse Wave Velocity | Baseline | 946 cm/sec | Standard Error 62 |
| Sodium Nitrite 160 mg/d | Baseline and Week 10 Aortic Pulse Wave Velocity | Week 10 | 942 cm/sec | Standard Error 77 |
Secondary
Baseline and Week 10 Plasma Nitrite Concentrations
Time frame: Baseline (Week 0), Week 10
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Baseline and Week 10 Plasma Nitrite Concentrations | Week 10 | 0.261 micromolar | Standard Error 0.051 |
| Placebo | Baseline and Week 10 Plasma Nitrite Concentrations | Baseline | 0.201 micromolar | Standard Error 0.066 |
| Sodium Nitrite 80 mg/d | Baseline and Week 10 Plasma Nitrite Concentrations | Week 10 | 0.412 micromolar | Standard Error 0.066 |
| Sodium Nitrite 80 mg/d | Baseline and Week 10 Plasma Nitrite Concentrations | Baseline | 0.209 micromolar | Standard Error 0.053 |
| Sodium Nitrite 160 mg/d | Baseline and Week 10 Plasma Nitrite Concentrations | Week 10 | 0.369 micromolar | Standard Error 0.064 |
| Sodium Nitrite 160 mg/d | Baseline and Week 10 Plasma Nitrite Concentrations | Baseline | 0.155 micromolar | Standard Error 0.044 |