Effects of Tetrahydrobiopterin on Blood Pressure

• Status: Completed
• Trial end date: 2005-12-01
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Emory University
• Collaborator: American Heart Association

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