Hypertension
Conditions
Brief summary
The investigators hypothesize that reducing salt in the diet will improve the function of blood vessels in middle aged and older adults with moderately elevated systolic blood pressure, by increasing the amount of BH4 and nitric oxide in your blood vessels and reducing the amount of oxidative stress.
Detailed description
The improvement in blood vessel function will be determined over a 10 week period. Subjects will be randomly assigned to either a 'low salt' condition (placebo pills + 1200 mg dietary sodium) or a 'normal salt' condition (2300 mg sodium chloride pills + 1200 mg dietary sodium) and monitored for 5 weeks. After the initial set of 5 weeks, the subjects are switched into the opposite condition, completing the cross-over study design. During weeks 1-4 and 6-9, subjects are monitored weekly with 24 hour urine collections and diet logs. The assessment of the primary outcome (blood vessel function) is completed during weeks 5 and 10. BH4 and ascorbic acid are also administered during weeks 5 and 10 to measure the effects of sodium intake on endogenous BH4 levels and vascular oxidative stress.
Interventions
The normal salt condition is maintained with 2300 mg / day in the form of slowly released salt (NaCl) tablets.
OTHERplacebo
Placebo tablets are administered to maintain the low sodium condition.
Sponsors
National Institute on Aging (NIA)
University of Colorado, Boulder
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
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 * SBP 130-159 mmHg
Exclusion criteria
* Have been sick with an infection in the past two weeks * Are currently sick or have ongoing health problems such as kidney or CVD * Have lost more than 11 lbs. in the last 3 months * Are taking any type of antioxidants * Smoke or have alcohol problems * Have blood glucose levels higher than 126 mg/dL * Have resting SBP below or less than 100 mmHg or greater than 159 mmHg * Have a resting diastolic blood pressure greater than 99 mmHg * Have a BMI greater than 40 kg/m\^2 * Are presently consuming less than 9 or greater than 18 grams of salt / day * Have a baseline FMD of greater than 6% * Are taking any of the following types of drugs: blood thinners, anti-seizure medications, ant-inflammatory drugs * Participate in any high endurance athletic training * Taking Hormone Replacement Therapy * Have not been post-menopausal for at least 1 year
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Improved Flow Mediated Dilation | Week 5 (after first condition of low salt or normal salt), Week 10 (after second condition, opposite to first) | FMD is analyzed at weeks 5 and 10 or after each condition in this cross-over study design. Subjects are randomly assigned to a low salt or normal salt condition for the first set of 5 weeks and then crossed over to the other condition for the second set of 5 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vascular Oxidative Stress | Immediately following acute infusion of ascorbic acid on Weeks 5 and 10 | Change in FMD following acute infusion of ascorbic acid (a dose known to scavenge superoxide) is measured at the end of 5 weeks of sodium condition (low and normal intake) as an index of vascular oxidative. |
| BH4 Bioavailability | Immediately following acute administration of BH4 on Weeks 5 and 10 | Change in FMD following acute oral tetrahydrobiopterin (BH4) is measured at the end of 5 weeks of sodium condition (low and normal intake) as an index of BH4 bioavailability. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Slow Sodium Tablets (Start) Subjects on a 1200 mg sodium diet are given 2300 mg sodium in the form of a slow sodium tablets to bring them back up to a normal salt intake. This is administered through 10 tablets day.
Subjects then cross-over to the placebo arm in the second half of the study. | 7 |
| Placebo (Start) Subjects on a 1200 mg salt diet are given placebo pills in order to maintain them on a low salt diet.
Subjects then cross over to the slow sodium tablet arm in the second half of the study. | 10 |
| Total | 17 |
Baseline characteristics
| Characteristic | Slow Sodium Tablets (Start) | Placebo (Start) | Total |
|---|---|---|---|
| Age, Continuous | 62 years STANDARD_DEVIATION 7 | 62 years STANDARD_DEVIATION 7 | 62 years STANDARD_DEVIATION 7 |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 17 | 0 / 17 |
| serious Total, serious adverse events | 0 / 17 | 0 / 17 |
Outcome results
Primary
Improved Flow Mediated Dilation
FMD is analyzed at weeks 5 and 10 or after each condition in this cross-over study design. Subjects are randomly assigned to a low salt or normal salt condition for the first set of 5 weeks and then crossed over to the other condition for the second set of 5 weeks.
Time frame: Week 5 (after first condition of low salt or normal salt), Week 10 (after second condition, opposite to first)
Population: All subjects are analyzed under each condition because of the cross-over design.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Sodium Diet | Improved Flow Mediated Dilation | 3.57 percentage dilation | Standard Deviation 1.59 |
| Low Sodium Diet. | Improved Flow Mediated Dilation | 6.01 percentage dilation | Standard Deviation 2.31 |
Secondary
BH4 Bioavailability
Change in FMD following acute oral tetrahydrobiopterin (BH4) is measured at the end of 5 weeks of sodium condition (low and normal intake) as an index of BH4 bioavailability.
Time frame: Immediately following acute administration of BH4 on Weeks 5 and 10
Population: BH4 could not be administered to 3 participants due to canceled visits.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Sodium Diet | BH4 Bioavailability | 3.57 percentage dilation | Standard Deviation 1.69 |
| Low Sodium Diet. | BH4 Bioavailability | 6.01 percentage dilation | Standard Deviation 2.31 |
| Normal Sodium Ascorbic Acid | BH4 Bioavailability | 5.78 percentage dilation | Standard Deviation 2.02 |
| Low Sodium Ascorbic Acid | BH4 Bioavailability | 6.11 percentage dilation | Standard Deviation 2.32 |
Secondary
Vascular Oxidative Stress
Change in FMD following acute infusion of ascorbic acid (a dose known to scavenge superoxide) is measured at the end of 5 weeks of sodium condition (low and normal intake) as an index of vascular oxidative.
Time frame: Immediately following acute infusion of ascorbic acid on Weeks 5 and 10
Population: Ascorbic acid is missing in one participant due to a failed i.v.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Sodium Diet | Vascular Oxidative Stress | 3.57 percentage dilation | Standard Deviation 1.69 |
| Low Sodium Diet. | Vascular Oxidative Stress | 6.01 percentage dilation | Standard Deviation 2.31 |
| Normal Sodium Ascorbic Acid | Vascular Oxidative Stress | 4.90 percentage dilation | Standard Deviation 2.84 |
| Low Sodium Ascorbic Acid | Vascular Oxidative Stress | 5.51 percentage dilation | Standard Deviation 2.36 |