Oral 6R-BH4 for the Treatment of Isolated Systolic Hypertension and Endothelial Dysfunction

Study Overview
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Brief Summary
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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
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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

Official Title
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Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation, Parallel Study of Oral 6R-BH4 in Subjects With Isolated Systolic Hypertension and Endothelial Dysfunction

Conditions
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Isolated Systolic Hypertension, Endothelial Dysfunction

Intervention / Treatment
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* Drug: 6R-BH4
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Drug<br> | Drug: 6R-BH4<br>* 6R-BH4 5mg/kg or Placebo BID for four weeks and then 8 week dose-escalation period<br>|
| Placebo Comparator: Placebo Comparator<br> | Other: Placebo<br>* placebo given BID for entire length of study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the Efficacy of 6R-BH4 Versus Placebo to Improve Endothelia Function |  | 4-6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Isolated Systolic Hypertension with Endothelial Dysfunction