Pulmonary Arterial HypertensionPhase 1NCT00435331
6R-BH4 Pulmonary Arterial Hypertension Study
A Phase 1 study testing sapropterin dihydrochloride (6R-BH4) in people with Pulmonary Arterial Hypertension, run by Vanderbilt University at 1 site in United States.
Trial summary
The purpose of this study is to determine whether the addition of sapropterin dihydrochloride (6R-BH4) to existing treatment has any effect in patients with pulmonary arterial hypertension (PAH). Patients with PAH have low levels of a substance called nitric oxide (NO). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- sapropterin dihydrochloride (6R-BH4)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2008to Oct 2008
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Documented diagnosis of PAH, defined as mean pulmonary arterial pressure > 25 mm Hg (measured by catheter).
- PAH is primary (idiopathic) or is secondary and caused by collagen vascular disease, congenital heart disease, or thromboembolic disease.
- Modified New York Heart Association (NYHA) classification I, II, or III that has been stable for at least 8 weeks prior to enrollment.
- 6MW distance, as performed at screening or within three months (12 weeks) prior to screening, of ≥ 200 and ≤ 500 meters.
- Receiving stable doses of one or more medications that are approved for treatment of PAH, except for any agents specifically prohibited by this protocol, for a minimum of 12 consecutive weeks before enrollment. Note: anticoagulant therapy can be adjusted according to target INR.
- Receiving stable doses of concomitant medication for other conditions, except agents specifically prohibited by the protocol.
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- At least 18 years of age and willing and able to complete an informed consent form.
- Sexually active subjects must be willing to use an acceptable method of contraception while participating in the study.
- Females of childbearing potential must have a negative pregnancy test at screening and be willing to have additional pregnancy tests during the study.
Who cannot join
- Previous treatment with any formulation of BH4.
- Known allergy or hypersensitivity to any excipient of 6R BH4.
- History of systemic hypotension, defined as systolic BP < 100 mm Hg and/or diastolic BP < 60 mm Hg.
- Treatment at screening or perceived need for treatment during the course of the study with any of the following:
- intravenous epoprostenol
- inhaled iloprost
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- subcutaneous treprostinil
- levodopa
- any PDE 3 inhibitor, such as cilostazol or milrinone
- any drug known to inhibit folate metabolism, such as methotrexate (eg, TrexallR), tomizine, trimethoprim, sulfanilamide, deoxycoformycin
- nitrates
- Diet supplementation with L-arginine or L-citrulline within 30 days of enrollment.
- Diet supplementation with high doses (> 3 times the recommended daily allowance) of antioxidants, such as Vitamin C.
- Use of any investigational product or device within 30 days prior to screening, or known requirement for any investigational agent prior to completion of all scheduled study assessments.
- Known to be positive for human immunodeficiency virus (HIV).
- An additional medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the investigator, may significantly interfere with study compliance, including all prescribed evaluations and follow-up activities. Concurrent disease or condition that may interfere with study participation or safety include bleeding disorders, arrhythmia, organ transplant (other than lung), organ failure, current neoplasm, poorly controlled diabetes mellitus, and serious neurological disorders.
- Serum creatinine > 2.0 mg/dL (180 μM/L) or hepatic enzyme levels more than 2 times the upper limit of normal.
- Pregnant or lactating at screening, or planning to become pregnant (self or partner) at any time during study.
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt Medical Center
Nashville, Tennessee, 37232
About this study
Official title: A Phase 1, Multicenter, Open-label, Dose-escalation Study to Evaluate the Safety and Efficacy of 6R-BH4 in Subjects With Pulmonary Arterial Hypertension
The purpose of this study is to determine whether the addition of sapropterin dihydrochloride (6R-BH4) to existing treatment has any effect in patients with pulmonary arterial hypertension (PAH). Patients with PAH have low levels of a substance called nitric oxide (NO). Tetrahydrobiopterin (BH4) is a substance produced by the body that is an essential requirement in the formation of NO. NO is thought to be helpful in keeping blood vessels in the lung healthy. 6R-BH4 is an experimental (unproven) medicine made in the lab that is very much like the BH4 that our own body makes. The researchers are investigating whether 6R-BH4 can be added safely to current treatment for PAH and whether there is any evidence of benefit from its use. The study will take approximately one year to complete from the time recruitment begins.
The primary objective of the study is to evaluate the safety of oral 6R-BH4, administered in escalating doses in addition to standard care, in subjects with pulmonary arterial hypertension (PAH).
Read more
The secondary objective of the study is to evaluate change in biochemical markers of endothelial dysfunction and nitric oxide synthetase activity (coupled and uncoupled) in subjects with PAH receiving escalating doses of oral 6R-BH4 in addition to standard care.
The third objective of the study is to evaluate change in biomarkers of disease progression, 6-minute walk (6MW) distance, Borg dyspnea scores, and quality of life (QOL) measures in subjects with PAH receiving escalating doses of oral 6R-BH4 in addition to standard care.
Read the detailed description
The primary objective of the study is to evaluate the safety of oral 6R-BH4, administered in escalating doses in addition to standard care, in subjects with pulmonary arterial hypertension (PAH).
The secondary objective of the study is to evaluate change in biochemical markers of endothelial dysfunction and nitric oxide synthetase activity (coupled and uncoupled) in subjects with PAH receiving escalating doses of oral 6R-BH4 in addition to standard care.
The third objective of the study is to evaluate change in biomarkers of disease progression, 6-minute walk (6MW) distance, Borg dyspnea scores, and quality of life (QOL) measures in subjects with PAH receiving escalating doses of oral 6R-BH4 in addition to standard care.
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- sapropterin dihydrochloride (6R-BH4)
- Keywords
- Pulmonary Arterial Hypertension, PPH
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sapropterin dihydrochloride (6R-BH4)Drug
2.5 mg/kg/day for two weeks, 5 mg/kg/day for two weeks, 10 mg/kg/day for four weeks, then 20 mg/kg/day for two days
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Open Label Receives: Drug: sapropterin dihydrochloride (6R-BH4) |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the safety of oral 6R-BH4, administered in escalating doses in addition to standard care, in subjects with pulmonary arterial hypertension (PAH).
Measured: Up to 14 weeks
Secondary outcomes (2)
Change in biochemical markers of endothelial dysfunction and nitric oxide synthetase activity (coupled and uncoupled).
Measured: Up to 14 weeks
Change in biomarkers of disease progression, 6-minute walk (6MW) distance, Borg dyspnea scores, and quality of life (QOL) measures.
Measured: Up to 14 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Feb 2007 (estimated)
- Study startMar 2008
- Primary completionSep 2008
- Study completionOct 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), BioMarin Pharmaceutical
- Responsible party
- Principal investigator, Ivan Robbins, Vanderbilt University
- Investigators
- Ivan M. Robbins, MD, Principal investigator, Vanderbilt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00435331
- Sponsor's protocol ID
- WILK1
- Status last verified
- Jun 2013
- First submitted
- 12 Feb 2007
- Last updated
- 19 Jun 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Multicenter, Open-label, Dose-escalation Study to Evaluate the Safety and Efficacy of 6R-BH4 in Subjects With Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT00435331
- Acronym / sponsor ID
- WILK1
- Conditions
- Pulmonary Arterial Hypertension
- Keywords
- Pulmonary Arterial Hypertension, PPH
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Vanderbilt UniversityUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), BioMarin Pharmaceutical
- Study start
- Mar 2008
- Primary completion
- Sep 2008 (actual)
- Study completion
- Oct 2008 (actual)
- First posted
- 14 Feb 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether the addition of sapropterin dihydrochloride (6R-BH4) to existing treatment has any effect in patients with pulmonary arterial hypertension (PAH). Patients with PAH have low levels of a substance called nitric oxide (NO). Tetrahydrobiopterin (BH4) is a substance produced by the body that is an essential requirement in the formation of NO. NO is thought to be helpful in keeping blood vessels in the lung healthy. 6R-BH4 is an experimental (unproven) medicine made in the lab that is very much like the BH4 that our own body makes. The researchers are investigating whether 6R-BH4 can be added safely to current treatment for PAH and whether there is any evidence of benefit from its use. The study will take approximately one year to complete from the time recruitment begins.
The primary objective of the study is to evaluate the safety of oral 6R-BH4, administered in escalating doses in addition to standard care, in subjects with pulmonary arterial hypertension (PAH).
The secondary objective of the study is to evaluate change in biochemical markers of endothelial dysfunction and nitric oxide synthetase activity (coupled and uncoupled) in subjects with PAH receiving escalating doses of oral 6R-BH4 in addition to standard care.
The third objective of the study is to evaluate change in biomarkers of disease progression, 6-minute walk (6MW) distance, Borg dyspnea scores, and quality of life (QOL) measures in subjects with PAH receiving escalating doses of oral 6R-BH4 in addition to standard care.
Detailed description
The primary objective of the study is to evaluate the safety of oral 6R-BH4, administered in escalating doses in addition to standard care, in subjects with pulmonary arterial hypertension (PAH).
The secondary objective of the study is to evaluate change in biochemical markers of endothelial dysfunction and nitric oxide synthetase activity (coupled and uncoupled) in subjects with PAH receiving escalating doses of oral 6R-BH4 in addition to standard care.
The third objective of the study is to evaluate change in biomarkers of disease progression, 6-minute walk (6MW) distance, Borg dyspnea scores, and quality of life (QOL) measures in subjects with PAH receiving escalating doses of oral 6R-BH4 in addition to standard care.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: sapropterin dihydrochloride (6R-BH4)Open Label |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Documented diagnosis of PAH, defined as mean pulmonary arterial pressure > 25 mm Hg (measured by catheter).
- PAH is primary (idiopathic) or is secondary and caused by collagen vascular disease, congenital heart disease, or thromboembolic disease.
- Modified New York Heart Association (NYHA) classification I, II, or III that has been stable for at least 8 weeks prior to enrollment.
- 6MW distance, as performed at screening or within three months (12 weeks) prior to screening, of ≥ 200 and ≤ 500 meters.
- Receiving stable doses of one or more medications that are approved for treatment of PAH, except for any agents specifically prohibited by this protocol, for a minimum of 12 consecutive weeks before enrollment. Note: anticoagulant therapy can be adjusted according to target INR.
Key exclusion criteria (18 listed)
- Previous treatment with any formulation of BH4.
- Known allergy or hypersensitivity to any excipient of 6R BH4.
- History of systemic hypotension, defined as systolic BP < 100 mm Hg and/or diastolic BP < 60 mm Hg.
- Treatment at screening or perceived need for treatment during the course of the study with any of the following:
- Diet supplementation with L-arginine or L-citrulline within 30 days of enrollment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sapropterin dihydrochloride (6R-BH4)2.5 mg/kg/day for two weeks, 5 mg/kg/day for two weeks, 10 mg/kg/day for four weeks, then 20 mg/kg/day for two days | Drug | 1 |
Primary outcome
To evaluate the safety of oral 6R-BH4, administered in escalating doses in addition to standard care, in subjects with pulmonary arterial hypertension (PAH).
Time frame: Up to 14 weeks
2 secondary outcomes
Change in biochemical markers of endothelial dysfunction and nitric oxide synthetase activity (coupled and uncoupled).
Time frame: Up to 14 weeks
Change in biomarkers of disease progression, 6-minute walk (6MW) distance, Borg dyspnea scores, and quality of life (QOL) measures.
Time frame: Up to 14 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ivan M. Robbins, MD principal investigator
Vanderbilt University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing sapropterin dihydrochloride (6R-BH4) in people with Pulmonary Arterial Hypertension, run by Vanderbilt University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate the safety of oral 6R-BH4, administered in escalating doses in addition to standard care, in subjects with pulmonary arterial hypertension (PAH). (time frame: Up to 14 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jun 2013; AzTrials last refreshed its copy on 4 Nov 2026.