Claudication, IntermittentPhase 1ATLASNCT04800692
The Effects of ATLAS Therapy on Nitric Oxide Bioavailability in Patients With Intermittent Claudication
A Phase 1 study testing Tetrahydrobiopterin 10 mg/kg, Tetrahydrobiopterin 20 mg/kg and L-Ascorbate in people with Claudication, Intermittent and Peripheral Artery Disease, run by Louis Messina at 1 site in United States.
Trial summary
This study will focus on people with claudication from peripheral arterial disease. The investigators are researching whether a multicomponent therapeutic can increase the production of Nitric Oxide in the blood and whether that leads to an improvement in pain free walking distance and overall physical activity. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Claudication, Intermittent, Peripheral Artery Disease, Peripheral Vascular Diseases
- What is being tested?
- Tetrahydrobiopterin 10 mg/kg, Tetrahydrobiopterin 20 mg/kg and L-Ascorbate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jun 2021to Dec 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- PAD as demonstrated by an ABI <0 .9 in one leg or TBI less than <0.7 in patients with an ABI >1.3 (non compressible vessels)
- Rutherford Classification II, III
- Age >18 years old
- Willingness to discontinue phosphodiesterase (PDE) 5 inhibitors such as Viagra, Cialis, Levitra, Revatio
- Willingness to discontinue phosphodiesterase (PDE) 3inhibitors cilostazol, milrinone or Vesnarinone
- Willing and able to comply with all study procedures
- Willing and able to provide informed consent
- Sexually active subjects willing to use an acceptable method of contraception while participating in the study
Who cannot join
- Hypotension defined as a systolic blood pressure less than 100mmhg systolic at screening or baseline visit
- Critical Leg Ischemia (Rutherford Classification IV, V, VI)
- Surgical intervention to alleviate symptoms of claudication in the study leg within the past 6 months or any endovascular interventions within 3 months or who is scheduled to undergo surgical revascularization in the next 6 month
- Walking limited by reasons other than claudication (e.g. arthritis, lung disease, severe neuropathy, lower extremity amputation except single digits)
- Serum creatinine >1.5mg/dl or Hepatic enzymes >2X the upper limit of normal
- Serum potassium greater than 5.0 or use of a potassium sparing diuretic at screening
Show all 19Show fewer
- Pregnant, breast feeding or planning to become pregnant (subject or partner) at any time during the study.
- Myocardial Infarction, Cerebrovascular Accident or deep vein thrombosis within 12 months of screening
- Known history of nephrolithiasis
- History of ever having a seizure
- Concurrent disease or condition that would interfere with study participation or safety such as bleeding disorders, organ transplant, long term immunosuppression (excluding inhaled steroids), current neoplasm or severe gastroesophageal reflux
- History of vertigo or syncope within the past 10 years
- Enrollment in another drug or device study within 30 days of screening
- Required treatment with a drug known to inhibit folate metabolism (e.g. Methotrexate)
- Taking any of the following medications; PDE3 Inhibitors, PDE5 inhibitors, trental, nitrates, ginkgo biloba, levodopa, warfarin,
- Axillary lymph node dissection
- Presence of an amputation except single digits in either leg
- Preexisting illness that limits ambulation such as severe COPD, class III-IV heart failure, severe arthritis or back pain
- Glucose-6-dehydrogenase deficiency
Trial locations and contacts
1 site in 1 country.
United States1 site
UMASS Memorial Healthcare - University Campus
Worcester, Massachusetts, 01655
About this study
Official title: The Effects of ATLAS (Arginine Tetrahydrobiopterin L-Ascorbate) Therapy on Nitric Oxide Bioavailability and Pain-free Walking in Patients With Intermittent Claudication
This study will focus on people with claudication from peripheral arterial disease. The investigators are researching whether a multicomponent therapeutic can increase the production of Nitric Oxide in the blood and whether that leads to an improvement in pain free walking distance and overall physical activity.
Read the detailed description
The primary objective of this study is to show that ATLAS Therapy, (L-Arginine; Tetrahydrobiopterin; L-Ascorbate) is bioavailable in humans and exerts a measurable effect on its in vivo biological signature, Flow Mediated Vasodilation (FMD) in people with intermittent claudication caused by peripheral arterial disease. This will be a Phase I / dose finding study. All subjects will receive 2 different drug doses of the Kuvan the first 45 days they will receive 10 mg/kg/day. The second 45 days they will receive 20/mg/kg/day.
- Being tested
- Tetrahydrobiopterin 10 mg/kg, Tetrahydrobiopterin 20 mg/kg, L-Ascorbate, L-Arginine
- Medical subject headings
- Intermittent Claudication, Peripheral Arterial Disease, Peripheral Vascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tetrahydrobiopterin 10 mg/kgDrug
Also called sapropterin, kuvan
10mg/kg of Tetrahydrobiopterin daily.
Tetrahydrobiopterin 20 mg/kgDrug
Also called sapropterin, kuvan
20mg/kg of Tetrahydrobiopterin daily.
L-AscorbateDrug
3300 mg of l-ascorbate once daily
L-ArginineDrug
3400mg of l-arginine once daily
| Study group | Role | What they receive |
|---|---|---|
| Tetrahydrobiopterin Dose 1 (Day 0 to 44) | Experimental | All subjects will receive 3300mg l-Ascorbate , l-Arginine 3400mg and 10mg/kg of Tetrahydrobiopterin once a day. Receives: Drug: Tetrahydrobiopterin 10 mg/kg; Drug: L-Ascorbate; Drug: L-Arginine |
| Tetrahydrobiopterin Dose 2 (Day 45 to 90) | Experimental | All subjects will receive 3300mg l-Ascorbate, l-Arginine 3400mg and 20mg/kg of Tetrahydrobiopterin once a day. Receives: Drug: Tetrahydrobiopterin 20 mg/kg; Drug: L-Ascorbate; Drug: L-Arginine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Nitric Oxide bioavailability
Nitric Oxide bioavailability as measured by flow mediated dilatation (FMD).
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2021
- Study start15 Jun 2021
- Primary completionJul 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Claudication, IntermittentStudies 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
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- All subjects will receive the same starting dose of the 3 components which will be escalated at day 45.
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Louis Messina
- Sponsor type
- University, hospital or other
- Collaborators
- BioMarin Pharmaceutical
- Responsible party
- Sponsor-investigator, Louis Messina, University of Massachusetts, Worcester
- Investigators
- Louis M Messina, MD, Principal investigator, UMASS Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04800692
- Sponsor's protocol ID
- H00012734
- Acronym
- ATLAS
- Status last verified
- Apr 2026
- First submitted
- 11 Mar 2021
- Last updated
- 15 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of ATLAS (Arginine Tetrahydrobiopterin L-Ascorbate) Therapy on Nitric Oxide Bioavailability and Pain-free Walking in Patients With Intermittent Claudication
- ClinicalTrials.gov ID
- NCT04800692
- Acronym / sponsor ID
- ATLAS / H00012734
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Louis MessinaUniversity, hospital or other
- Collaborators
- BioMarin Pharmaceutical
- Study start
- 15 Jun 2021 (actual)
- Primary completion
- Jul 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 16 Mar 2021 (actual)
- 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.
This study will focus on people with claudication from peripheral arterial disease. The investigators are researching whether a multicomponent therapeutic can increase the production of Nitric Oxide in the blood and whether that leads to an improvement in pain free walking distance and overall physical activity.
Detailed description
The primary objective of this study is to show that ATLAS Therapy, (L-Arginine; Tetrahydrobiopterin; L-Ascorbate) is bioavailable in humans and exerts a measurable effect on its in vivo biological signature, Flow Mediated Vasodilation (FMD) in people with intermittent claudication caused by peripheral arterial disease. This will be a Phase I / dose finding study. All subjects will receive 2 different drug doses of the Kuvan the first 45 days they will receive 10 mg/kg/day. The second 45 days they will receive 20/mg/kg/day.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- All subjects will receive the same starting dose of the 3 components which will be escalated at day 45.
| Arm | Type | Receives |
|---|---|---|
| Tetrahydrobiopterin Dose 1 (Day 0 to 44) | Experimental | Drug: Tetrahydrobiopterin 10 mg/kg, Drug: L-Ascorbate, Drug: L-ArginineAll subjects will receive 3300mg l-Ascorbate , l-Arginine 3400mg and 10mg/kg of Tetrahydrobiopterin once a day. |
| Tetrahydrobiopterin Dose 2 (Day 45 to 90) | Experimental | Drug: Tetrahydrobiopterin 20 mg/kg, Drug: L-Ascorbate, Drug: L-ArginineAll subjects will receive 3300mg l-Ascorbate, l-Arginine 3400mg and 20mg/kg of Tetrahydrobiopterin once a day. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- PAD as demonstrated by an ABI <0 .9 in one leg or TBI less than <0.7 in patients with an ABI >1.3 (non compressible vessels)
- Rutherford Classification II, III
- Age >18 years old
- Willingness to discontinue phosphodiesterase (PDE) 5 inhibitors such as Viagra, Cialis, Levitra, Revatio
- Willingness to discontinue phosphodiesterase (PDE) 3inhibitors cilostazol, milrinone or Vesnarinone
Key exclusion criteria (19 listed)
- Hypotension defined as a systolic blood pressure less than 100mmhg systolic at screening or baseline visit
- Critical Leg Ischemia (Rutherford Classification IV, V, VI)
- Surgical intervention to alleviate symptoms of claudication in the study leg within the past 6 months or any endovascular interventions within 3 months or who is scheduled to undergo surgical revascularization in the next 6 month
- Walking limited by reasons other than claudication (e.g. arthritis, lung disease, severe neuropathy, lower extremity amputation except single digits)
- Serum creatinine >1.5mg/dl or Hepatic enzymes >2X the upper limit of normal
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 |
|---|---|---|
| Tetrahydrobiopterin 10 mg/kgAlso: sapropterin, kuvan10mg/kg of Tetrahydrobiopterin daily. | Drug | Tetrahydrobiopterin Dose 1 (Day 0 to 44) |
| Tetrahydrobiopterin 20 mg/kgAlso: sapropterin, kuvan20mg/kg of Tetrahydrobiopterin daily. | Drug | Tetrahydrobiopterin Dose 2 (Day 45 to 90) |
| L-Ascorbate3300 mg of l-ascorbate once daily | Drug | Tetrahydrobiopterin Dose 1 (Day 0 to 44), Tetrahydrobiopterin Dose 2 (Day 45 to 90) |
| L-Arginine3400mg of l-arginine once daily | Drug | Tetrahydrobiopterin Dose 1 (Day 0 to 44), Tetrahydrobiopterin Dose 2 (Day 45 to 90) |
Primary outcome
Nitric Oxide bioavailability
Time frame: 90 days
Nitric Oxide bioavailability as measured by flow mediated dilatation (FMD).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2026.
- Individual participant dataSharing planned: No
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Personalised Multicomponent Exercise Programme in Peripheral Arterial Disease
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Ramipril Treatment of Claudication: Oxidative Damage and Muscle Fibrosis
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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.
Louis M Messina, MD principal investigator
UMASS Medical School
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 Tetrahydrobiopterin 10 mg/kg, Tetrahydrobiopterin 20 mg/kg and L-Ascorbate in people with Claudication, Intermittent and Peripheral Artery Disease, run by Louis Messina 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 8 inclusion and 19 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: under way, not looking for participants, as of the sponsor's last update on 15 Apr 2026. 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?
This study is still under way. Results are not available in the source record yet.
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?
Nitric Oxide bioavailability (time frame: 90 days). 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 15 Apr 2026.