JNC 7 Stage I Hypertension, Pre-hypertension
Conditions
Keywords
Pre-hypertension, JNC 7 stage I hypertension
Brief summary
We propose a novel intervention for reducing BP that could have a preferential impact in patients with hyperuricemia and gout. There is a great need for new anti-hypertensives, particularly among those with gout. The proposed study is novel in its plans to investigate the physiologic mechanisms through which urate contributes to vascular disease and by which ULT may contribute to BP reduction. Also innovative, we will: 1) determine to what extent the described benefit of lowering serum urate extends beyond the adolescent population previously studied into young adults, 2) test whether a urate-lowering approach will benefit individuals that do not yet meet the current definition of hyperuricemia and do not have gout, and 3) begin to explore potential mechanisms for the higher prevalence of hypertension among African-Americans. If successful, this work could translate to the standard of clinical care and to health care recommendations for the population as a whole.
Interventions
DRUGAllopurinol
Participants who received allopurinol as urate lowering therapy, at a daily dose of 300 mg once daily by mouth for a 4 week duration.
DRUGPlacebo
Participants who received placebo tablet (matching Allopurinol 300 mg) daily by mouth for a 4 week duration.
Sponsors
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
University of Alabama at Birmingham
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Pre-hypertension or stage I hypertension, defined as the following after the mean of two clinic measurements: * Systolic blood pressure (SBP) ≥ 120 and \<160 or; * Diastolic blood pressure (DBP) ≥ 80 and \< 100 * Serum urate ≥ 5.0 mg/dL for men or ≥ 4.0 mg/dL for women * Age 18-40
Exclusion criteria
* Any current pharmacological treatment for hypertension, including diuretics (calcium channel blockers at stable doses were later allowed) * Estimated glomerular filtration rate \< 60 mL/min/1.73m2 * Current use of any urate-lowering therapy or statins * Prior diagnosis of gout or past use of urate-lowering therapy for gout * Prior diagnosis of diabetes * Pregnancy, or recent delivery or last trimester pregnancy loss more recent than 3 months * Active smokers * Immune-suppressed individuals including transplant recipients or current use of azathioprine. * Leucopenia with absolute white cell count \< 3000 /mL, anemia with hemoglobin \< 12 g/dL, or thrombocytopenia with platelet count \< 150,000/mL * Individuals of Han Chinese or Thai descent with HLAB5801 genetic phenotype * Serious medical condition that at investigator's judgment precludes utilization of a fixed dose of allopurinol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Systolic Blood Pressure (SBP) | 4 weeks (pre-treatment vs. post-treatment SBP) | Compare systolic blood pressure (SBP) captured by wearing a 24 hour ambulatory blood pressure monitor during each phase of treatment (allopurinol 300 mg/day PO or placebo). Change in systolic blood pressure is calculated by comparing SBP at the end of each treatment phase to pre-treatment values. |
| Change in Flow-mediated Arterial Vasodilation | 4 weeks (pre-treatment vs. post-treatment FMD Values (%)) | Compare endothelial function as indexed by flow-mediated arterial vasodilation (FMD) within each phase of treatment (allopurinol 300 mg/day PO or placebo). Percent (%) change in FMD is calculated by comparing FMD (%) at the end of each treatment phase to pre-treatment values. |
| Change in Serum Levels of High Sensitivity C-reactive Protein | 4 weeks (pre-treatment vs. post-treatment serum levels) | Serum level of high sensitivity C-reactive protein will be reported as a change during treatment phase (allopurinol 300 mg/day PO or placebo). Change in serum level of C-reactive protein is calculated by comparing serum values at the end of each treatment phase to pre-treatment levels. |
Countries
United States
Participant flow
Pre-assignment details
Participants completed a 2-4 week placebo run-in prior to assignment to study arm.
Participants by arm
| Arm | Count |
|---|---|
| Overall Participants will be asked to take 4 weeks of allopurinol or placebo, then will crossover to the other drug (after 2-4 week washout period) and take either allopurinol or placebo for an additional 4 weeks.
Placebo: The subjects will be randomized to receive allopurinol as urate lowering therapy (ULT), at a daily dose of 300 mg once daily by mouth or placebo. Participants will be asked to take 4 weeks of allopurinol or placebo, then will crossover to the other drug (after 4 week washout period) and take either allopurinol or placebo for an additional 4 weeks. | 99 |
| Total | 99 |
Baseline characteristics
| Characteristic | Overall |
|---|---|
| Age, Continuous | 28.0 years STANDARD_DEVIATION 7 |
| Body Mass Index | 30.8 kg/m^2 STANDARD_DEVIATION 7.7 |
| Diastolic Blood Pressure | 81.3 mm Hg STANDARD_DEVIATION 9.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 96 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Flow Mediated Dilation | 10.3 percentage of dilation STANDARD_DEVIATION 5.2 |
| high sensitivity C-reactive protein (hs-CRP) | 3.5 mg/L STANDARD_DEVIATION 4.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 40 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 52 Participants |
| Serum urate (mg/dL) | 5.8 mg/dL STANDARD_DEVIATION 1.2 |
| Sex: Female, Male Female | 37 Participants |
| Sex: Female, Male Male | 62 Participants |
| Systolic Blood Pressure | 127 mm Hg STANDARD_DEVIATION 11.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 99 | 0 / 99 |
| other Total, other adverse events | 12 / 99 | 12 / 99 |
| serious Total, serious adverse events | 0 / 99 | 0 / 99 |
Outcome results
Primary
Change in Flow-mediated Arterial Vasodilation
Compare endothelial function as indexed by flow-mediated arterial vasodilation (FMD) within each phase of treatment (allopurinol 300 mg/day PO or placebo). Percent (%) change in FMD is calculated by comparing FMD (%) at the end of each treatment phase to pre-treatment values.
Time frame: 4 weeks (pre-treatment vs. post-treatment FMD Values (%))
Population: Missing data was handled with a multiple imputation approach
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Allopurinol Phase | Change in Flow-mediated Arterial Vasodilation | 2.5 percent change | Standard Error 0.55 |
| Placebo Phase | Change in Flow-mediated Arterial Vasodilation | -0.1 percent change | Standard Error 0.42 |
p-value: <0.001paired t-test
Primary
Change in Serum Levels of High Sensitivity C-reactive Protein
Serum level of high sensitivity C-reactive protein will be reported as a change during treatment phase (allopurinol 300 mg/day PO or placebo). Change in serum level of C-reactive protein is calculated by comparing serum values at the end of each treatment phase to pre-treatment levels.
Time frame: 4 weeks (pre-treatment vs. post-treatment serum levels)
Population: Data reported is imputed for missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Allopurinol Phase | Change in Serum Levels of High Sensitivity C-reactive Protein | 0.6 mg/L | Standard Error 0.39 |
| Placebo Phase | Change in Serum Levels of High Sensitivity C-reactive Protein | 0.8 mg/L | Standard Error 0.82 |
p-value: 0.84paired t-test
Primary
Change in Systolic Blood Pressure (SBP)
Compare systolic blood pressure (SBP) captured by wearing a 24 hour ambulatory blood pressure monitor during each phase of treatment (allopurinol 300 mg/day PO or placebo). Change in systolic blood pressure is calculated by comparing SBP at the end of each treatment phase to pre-treatment values.
Time frame: 4 weeks (pre-treatment vs. post-treatment SBP)
Population: Missing data was handled with a multiple imputations approach
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Allopurinol Phase | Change in Systolic Blood Pressure (SBP) | -1.39 mm Hg | Standard Error 10 |
| Placebo Phase | Change in Systolic Blood Pressure (SBP) | -1.06 mm Hg | Standard Error 8.94 |
p-value: 0.83paired t-test