The Effects of ATLAS Therapy on Nitric Oxide Bioavailability in Patients With Intermittent Claudication

NCT04800692 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: H00012734
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Claudication, Intermittent; Peripheral Artery Disease; Peripheral Vascular Diseases

Outcome Measures

Primary Outcomes (1)

• Nitric Oxide bioavailability

  Nitric Oxide bioavailability as measured by flow mediated dilatation (FMD).

  90 days

Study Arms (2)

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.

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.

Drug: Tetrahydrobiopterin 20 mg/kg; Drug: L-Ascorbate; Drug: L-Arginine

Interventions

Tetrahydrobiopterin 10 mg/kg DRUG

10mg/kg of Tetrahydrobiopterin daily.

Also known as: sapropterin, kuvan

Tetrahydrobiopterin Dose 1 (Day 0 to 44)

Tetrahydrobiopterin 20 mg/kg DRUG

20mg/kg of Tetrahydrobiopterin daily.

Also known as: sapropterin, kuvan

Tetrahydrobiopterin Dose 2 (Day 45 to 90)

L-Ascorbate DRUG

3300 mg of l-ascorbate once daily

Tetrahydrobiopterin Dose 1 (Day 0 to 44); Tetrahydrobiopterin Dose 2 (Day 45 to 90)

L-Arginine DRUG

3400mg of l-arginine once daily

Tetrahydrobiopterin Dose 1 (Day 0 to 44); Tetrahydrobiopterin Dose 2 (Day 45 to 90)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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,

Sponsors & Collaborators

• Louis Messina: lead
• BioMarin Pharmaceutical: collaborator

Study Sites (1)

UMASS Memorial Healthcare - University Campus

Worcester, Massachusetts, 01655, United States

Location

MeSH Terms

Conditions

Intermittent Claudication; Peripheral Arterial Disease; Peripheral Vascular Diseases

Interventions

sapropterin; Arginine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential

Study Officials

• Louis M Messina, MD

  UMASS Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: All subjects will receive the same starting dose of the 3 components which will be escalated at day 45.

Study Record Dates

• First Submitted: March 11, 2021
• First Posted: March 16, 2021
• Study Start: June 15, 2021
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)