Print

Purpose

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
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
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Tetrahydrobiopterin Dose 1 (Day 0 to 44) 		All subjects will receive 3300mg l-Ascorbate , l-Arginine 3400mg and 10mg/kg of Tetrahydrobiopterin once a day.
  • Drug: Tetrahydrobiopterin 10 mg/kg
    10mg/kg of Tetrahydrobiopterin daily.
    Other names:
    • sapropterin
    • kuvan
  • Drug: L-Ascorbate
    3300 mg of l-ascorbate once daily
  • Drug: L-Arginine
    3400mg of l-arginine once daily
Experimental
Tetrahydrobiopterin Dose 2 (Day 45 to 90) 		All subjects will receive 3300mg l-Ascorbate, l-Arginine 3400mg and 20mg/kg of Tetrahydrobiopterin once a day.
  • Drug: Tetrahydrobiopterin 20 mg/kg
    20mg/kg of Tetrahydrobiopterin daily.
    Other names:
    • sapropterin
    • kuvan
  • Drug: L-Ascorbate
    3300 mg of l-ascorbate once daily
  • Drug: L-Arginine
    3400mg of l-arginine once daily

Recruiting Locations

UMASS Memorial Healthcare - University Campus
Worcester, Massachusetts 01655
Contact:
Shauneen Valliere, MSN
508-856-1767
shauneen.valliere@umassmed.edu

More Details

Status
Recruiting
Sponsor
Louis Messina

Study Contact

Shauneen Valliere, MSN
508-856-1767
shauneen.valliere@umassmed.edu

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.