Endothelial Dysfunction, Isolated Systolic Hypertension
Conditions
Keywords
Isolated Systolic Hypertension with Endothelial Dysfunction
Brief summary
This study is designed to assess the safety and efficacy of twice-daily oral dosing of 6R-BH4 to improve endothelial function, reduce systolic blood pressure and reduce arterial stiffness.
Detailed description
By comparing values measured at different timepoints, the study is expected to provide insight regarding the ability of 6R-BH4, administered along with their currently prescribed antihypertension medications, to improve endothelial function, reduce SBP, and reduce arterial stiffness in patients with ISH and endothelial dysfunction
Interventions
DRUG6R-BH4
6R-BH4 5mg/kg or Placebo BID for four weeks and then 8 week dose-escalation period
OTHERPlacebo
placebo given BID for entire length of study
Sponsors
BioMarin Pharmaceutical
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* No change in prescribed antihypertension medications within the previous 30 days * Study staff able to visualize and measure the brachial artery diameter by high resolution vascular ultrasound required for FMD measurements * ISH with the following mean seated BP: SBP \> 145 and \< 180 mmHg. Diastolic blood pressure \< 90mmHg
Exclusion criteria
* Has known hypersensitivity to 6RBH4 or its excipients * Pregnant or breastfeeding at screening * Use of any investigational product or investigational medical device within 30 days prior to screening * Current disease or condition that would interfere with study participation or safety such as the following: heart failure, atrial fibrillation, aortic valve disease, bleeding disorders, history of repeated syncope or vertigo, severe GERD, GI ulcer, symptomatic coronary or peripheral vascular disease, arrhythmia, serious neurologic disorders including seizures, organ transplant or organ failure * Hypertension secondary to other medical conditions * Any severe comorbid condition that would limit life expectancy to \<6 months * Current use of any nicotine containing substances * History of drug or alcohol abuse * MI, stroke or surgery within 90 days before Screening Visit * CABG within 6 months before the Screening Visit * Serum creatinine \>2.0mg/dl or AST, ALT, GGT levels \>2times upper limit of normal * Concomitant treatment with: any drug known to inhibit folate metabolism, any phosphodiesterase-5 or -3 inhibitor * Previous treatment with any formulation of BH4
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Evaluate the Efficacy of 6R-BH4 Versus Placebo to Improve Endothelia Function | 4-6 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Evaluate the Efficacy of Oral 6R-BH4 Versus Dosage-equivalent Placebo to Improve Endothelia Function, to Reduce SBP, to Reduce Arterial Stiffness | 4-8 weeks |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants 6R-BH4: 6R-BH4 5mg/kg or Placebo BID for four weeks and then 8 week dose-escalation period
OR
Placebo: placebo given BID for entire length of study | 3 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | study terminated | 3 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Customized >=40, years | 3 Participants |
| Region of Enrollment United States | 3 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 0 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Evaluate the Efficacy of 6R-BH4 Versus Placebo to Improve Endothelia Function
Time frame: 4-6 weeks
Population: Due to difficulties recruiting, this study was terminated and no data was collected.
Secondary
Evaluate the Efficacy of Oral 6R-BH4 Versus Dosage-equivalent Placebo to Improve Endothelia Function, to Reduce SBP, to Reduce Arterial Stiffness
Time frame: 4-8 weeks
Population: Due to difficulties recruiting, this study was terminated and no data was collected.