NCT00208780

Brief 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

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
24

participants targeted

Target at P25-P50 for early_phase_1 hypertension

Timeline
Completed

Started Dec 2004

Shorter than P25 for early_phase_1 hypertension

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2004

Completed
10 months until next milestone

First Submitted

Initial submission to the registry

September 13, 2005

Completed
8 days until next milestone

First Posted

Study publicly available on registry

September 21, 2005

Completed
2 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2005

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2005

Completed
Last Updated

November 18, 2013

Status Verified

November 1, 2013

Enrollment Period

1 year

First QC Date

September 13, 2005

Last Update Submit

November 15, 2013

Conditions

Hypertension

Keywords

Oxidative StressEndothelium

Outcome Measures

Primary Outcomes (1)

  • Evaluate the effects of BH4 on BP

Secondary Outcomes (1)

  • Evaluate the effects of BH4 on vascular function

Study Arms (2)

Dose-response of oral BH4

EXPERIMENTAL

Eight subjects received 100 mg of oral BH4 twice a day and 8 received 200 mg twice daily.

Drug: Tetrahydrobiopterin

Onset & duration of action of oral BH4

EXPERIMENTAL

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

Interventions

TetrahydrobiopterinDRUG
Onset & duration of action of oral BH4

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Male or female patients without childbearing potential between the ages of 18 and 75 years
  • History of documented essential hypertension or newly diagnosed hypertension (BP \>140 mmHg systolic and/or 90 mmHg diastolic measured on 2 separate occasions)
  • 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.
  • 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.
  • 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.

You may not qualify if:

  • Female subjects with childbearing potential.
  • History of symptomatic coronary or peripheral vascular disease.
  • Known secondary causes for hypertension
  • Severe uncontrolled hypertension (BP \>180 mmHg systolic and /or 110 mmHg diastolic).
  • Severe co-morbid conditions which would limit life expectancy to less than 6 months.
  • Patients unable to give informed consent or adhere to the protocol.
  • Patients participating in another study protocol.
  • Patients with organ failure, creatinine \>2.5 mg/dL or hepatic enzymes \>2X normal
  • Recent (within 6 weeks) alteration of any concomitant therapy.
  • Presence of intercurrent illness
  • Bleeding disorders

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Emory University

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

  • Porkert M, Sher S, Reddy U, Cheema F, Niessner C, Kolm P, Jones DP, Hooper C, Taylor WR, Harrison D, Quyyumi AA. Tetrahydrobiopterin: a novel antihypertensive therapy. J Hum Hypertens. 2008 Jun;22(6):401-7. doi: 10.1038/sj.jhh.1002329. Epub 2008 Mar 6.

    PMID: 18322548RESULT

MeSH Terms

Conditions

Hypertension

Interventions

sapropterin

Condition Hierarchy (Ancestors)

Vascular DiseasesCardiovascular Diseases

Study Officials

  • Arshed A Quyyumi, MD

    Emory University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
early phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

September 13, 2005

First Posted

September 21, 2005

Study Start

December 1, 2004

Primary Completion

December 1, 2005

Study Completion

December 1, 2005

Last Updated

November 18, 2013

Record last verified: 2013-11

Locations

US(1)