Effects of ATLAS Therapy on Nitric Oxide Levels in Patients with Claudication

The Effects of ATLAS (Arginine Tetrahydrobiopterin L-Ascorbate) Therapy on Nitric Oxide Bioavailability and Pain-free Walking in Patients With Intermittent Claudication

Phase 1 Interventional University of Massachusetts, Worcester · NCT04800692

This study is testing if a new therapy can boost nitric oxide levels and help people with leg pain from peripheral artery disease walk more comfortably.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment10 (estimated)
Ages18 Years and up
SexAll
SponsorUniversity of Massachusetts, Worcester Academic / other
Drugs / interventionsMethotrexate
Locations1 site (Worcester, Massachusetts)
Trial IDNCT04800692 on ClinicalTrials.gov

What this trial studies

This study investigates the impact of ATLAS Therapy, which includes L-Arginine, Tetrahydrobiopterin, and L-Ascorbate, on nitric oxide bioavailability in patients suffering from intermittent claudication due to peripheral artery disease. The primary goal is to determine if this multicomponent therapy can enhance nitric oxide production and improve pain-free walking distance and overall physical activity. Participants will receive two different doses of the therapy over a 90-day period, allowing researchers to assess its effects on vascular function as measured by Flow Mediated Vasodilation (FMD).

Who should consider this trial

Good fit: Ideal candidates are adults over 18 with diagnosed peripheral artery disease and intermittent claudication.

Not a fit: Patients with critical leg ischemia or those who have had recent surgical interventions for claudication may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could significantly improve walking ability and quality of life for patients with intermittent claudication.

How similar studies have performed: Other studies have explored similar therapeutic approaches, but the specific combination used in this trial is novel.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* 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

Where this trial is running

Worcester, Massachusetts

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Claudication, IntermittentPeripheral Artery DiseasePeripheral Vascular Diseases
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.