Effects of Tetrahydrobiopterin on Blood Pressure

This study has been completed.
Sponsor:
Collaborator:
American Heart Association
Information provided by (Responsible Party):
Arshed A. Quyyumi, Emory University
ClinicalTrials.gov Identifier:
NCT00208780
First received: September 13, 2005
Last updated: November 15, 2013
Last verified: November 2013
  Purpose

Tetrahydrobiopterin (BH4) is a cofactor for the nitric oxide (NO) synthase enzymes, such that its insufficiency results in uncoupling of the enzyme, leading to release of superoxide rather than NO in disease states, including hypertension. We hypothesized that oral BH4 will reduce arterial blood pressure (BP) and improve endothelial function in hypertensive subjects. Oral BH4 was given to subjects with poorly controlled hypertension (BP >135/85 mm Hg) and weekly measurements of BP and endothelial function made. In Study 1, 5 or 10 mg kg−1 day−1 of BH4 (n=8) was administered orally for 8 weeks, and in Study 2, 200 and 400 mg of BH4 (n=16) was given in divided doses for 4 weeks


Condition Intervention Phase
Hypertension
Drug: Tetrahydrobiopterin
Phase 0

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effects of Tetrahydrobiopterin on Blood Pressure

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Evaluate the effects of BH4 on BP [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Evaluate the effects of BH4 on vascular function [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: December 2004
Study Completion Date: December 2005
Primary Completion Date: December 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose-response of oral BH4
Eight subjects received 100 mg of oral BH4 twice a day and 8 received 200 mg twice daily.
Drug: Tetrahydrobiopterin
Experimental: Onset & duration of action of oral BH4
Eight hypertensive subjects were assigned to either 5 mg kg−1 day−1 (n=4) or 10 mg kg−1 day−1 (n=4) of BH4, given in two divided doses orally for 8 weeks.
Drug: Tetrahydrobiopterin

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients without childbearing potential between the ages of 18 and 75 years
  2. History of documented essential hypertension or newly diagnosed hypertension (BP >140 mmHg systolic and/or 90 mmHg diastolic measured on 2 separate occasions)
  3. Patients on conventional anti-hypertensive therapy with poorly controlled hypertension (BP >135/85 mmHg). Their anti-hypertensive regimen will remain unchanged throughout the study period. Patients will not need to stop taking their prescribed anti-hypertensives.
  4. Controls will be recruited for part 2 of the study. These will be patients who meet the age and childbearing criteria above, who have no history of hypertension, arterial BP of <130 systolic and <85 diastolic, no evidence of diabetes mellitus, total cholesterol <240 and be non-smoking for at least six months.
  5. Patients can be at any stage of hypertension. They can be at any performance status. The only requirement will be that they be able to come to scheduled follow up visits either by themselves or with assistance. Patients will need to be able to give informed consent.

Exclusion Criteria:

  1. Female subjects with childbearing potential.
  2. History of symptomatic coronary or peripheral vascular disease.
  3. Known secondary causes for hypertension
  4. Severe uncontrolled hypertension (BP >180 mmHg systolic and /or 110 mmHg diastolic).
  5. Severe co-morbid conditions which would limit life expectancy to less than 6 months.
  6. Patients unable to give informed consent or adhere to the protocol.
  7. Patients participating in another study protocol.
  8. Patients with organ failure, creatinine >2.5 mg/dL or hepatic enzymes >2X normal
  9. Recent (within 6 weeks) alteration of any concomitant therapy.
  10. Presence of intercurrent illness
  11. Bleeding disorders
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00208780

Locations
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Emory University
American Heart Association
Investigators
Principal Investigator: Arshed A Quyyumi, MD Emory University
  More Information

Publications:
Responsible Party: Arshed A. Quyyumi, Professor, Emory University
ClinicalTrials.gov Identifier: NCT00208780     History of Changes
Other Study ID Numbers: 0476-2004
Study First Received: September 13, 2005
Last Updated: November 15, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Emory University:
Oxidative Stress
Endothelium

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on April 23, 2014