Clinical trial NCT04800692: The Effects of ATLAS Therapy on Nitric Oxide Bioavailability in Patients With Intermittent Claudication
Official title: The Effects of ATLAS (Arginine Tetrahydrobiopterin L-Ascorbate) Therapy on Nitric Oxide Bioavailability and Pain-free Walking in Patients With Intermittent Claudication
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Claudication, Intermittent
Peripheral Artery Disease
Peripheral Vascular Diseases
Lead sponsor: University of Massachusetts, Worcester
Sponsor class: OTHER
Collaborators: name: BioMarin Pharmaceutical
First posted: 2021-03-16
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: All subjects will receive the same starting dose of the 3 components which will be escalated at day 45.
Primary purpose: OTHER

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.

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.

Eligibility 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

Primary outcomes:
measure: Nitric Oxide bioavailability
timeFrame: 90 days
Secondary outcomes:
Other outcomes:
Locations:
city: Worcester
country: United States
facility: UMASS Memorial Healthcare - University Campus
state: Massachusetts
Study officials:
affiliation: UMASS Medical School
name: Louis M Messina, MD
role: PRINCIPAL_INVESTIGATOR
References: