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

Peripheral Artery Disease Clinical Trial

— ATLAS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04800692
• Other study ID #: H00012734
• Status: Recruiting
• Phase: Phase 1
• Start date: June 15, 2021
• Est. completion date: December 2025

Study information

• Verified date: November 2023
• Source: University of Massachusetts, Worcester
• Contact: Shauneen Valliere, MSN
• Phone: 508-856-1767
• Email: shauneen.valliere[@]umassmed.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: December 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Claudication, Intermittent
• Intermittent Claudication
• Peripheral Arterial Disease
• Peripheral Artery Disease
• Peripheral Vascular Diseases
• Vascular Diseases

Intervention

Drug:
• Tetrahydrobiopterin 10 mg/kg
10mg/kg of Tetrahydrobiopterin daily.
• Tetrahydrobiopterin 20 mg/kg
20mg/kg of Tetrahydrobiopterin daily.
• L-Ascorbate
3300 mg of l-ascorbate once daily
• L-Arginine
3400mg of l-arginine once daily

Locations

Country	Name	City	State
United States	UMASS Memorial Healthcare - University Campus	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Louis Messina	BioMarin Pharmaceutical

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Nitric Oxide bioavailability	Nitric Oxide bioavailability as measured by flow mediated dilatation (FMD).	90 days