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

Endothelial Dysfunction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00802893
• Other study ID #: NA_00014296
• Status: Terminated
• Phase: Phase 2
• First received: December 4, 2008
• Last updated: August 17, 2017
• Start date: December 2008
• Est. completion date: May 2009

Study information

• Verified date: August 2017
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: May 2009
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Endothelial Dysfunction
• Hypertension
• Isolated Systolic Hypertension

Intervention

Drug:
• 6R-BH4
6R-BH4 5mg/kg or Placebo BID for four weeks and then 8 week dose-escalation period

Other:
• Placebo
placebo given BID for entire length of study

Locations

Country	Name	City	State
United States	Johns Hopkins University	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	BioMarin Pharmaceutical

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate the Efficacy of 6R-BH4 Versus Placebo to Improve Endothelia Function		4-6 weeks
Secondary	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