Sodium Nitrite to Treat Arterial Aging

Study Overview
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Brief Summary
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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
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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.

Official Title
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Clinical Translation of Nitrite Therapy to Treat Arterial Aging in Humans

Conditions
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Vascular Aging

Intervention / Treatment
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* Drug: Placebo
* Drug: Sodium Nitrite


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>inert oral capsules (0 mg sodium nitrite morning; 0 mg sodium nitrite in evening) for 10 weeks | Drug: Placebo<br>* Sugar pill manufactured to mimic sodium nitrite capsules<br>|
| Experimental: Sodium Nitrite 80 mg/d<br>80 mg/day (40 mg in morning; 40 mg in evening) oral capsules for 10 weeks | Drug: Sodium Nitrite<br>* 80 mg/d or 160 mg/d<br>* Other names: TV1001;|
| Experimental: Sodium Nitrite 160 mg/d<br>160 mg/day (80 mg in morning; 80 mg in evening) oral capsules for 10 weeks | Drug: Sodium Nitrite<br>* 80 mg/d or 160 mg/d<br>* Other names: TV1001;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline (Week 0), Week 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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endothelial function, arterial stiffness, flow-mediated dilation, pulse wave velocity, sodium nitrite, aging, vascular diseases