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

Primary Purpose

Claudication, Intermittent, Peripheral Artery Disease, Peripheral Vascular Diseases

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Tetrahydrobiopterin 10 mg/kg
Tetrahydrobiopterin 20 mg/kg
L-Ascorbate
L-Arginine
Sponsored by
Louis Messina
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Claudication, Intermittent

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • UMASS Memorial Healthcare - University CampusRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Tetrahydrobiopterin Dose 1 (Day 0 to 44)

Tetrahydrobiopterin Dose 2 (Day 45 to 90)

Arm Description

All subjects will receive 3300mg l-Ascorbate , l-Arginine 3400mg and 10mg/kg of Tetrahydrobiopterin once a day.

All subjects will receive 3300mg l-Ascorbate, l-Arginine 3400mg and 20mg/kg of Tetrahydrobiopterin once a day.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
March 11, 2021
Last Updated
November 2, 2022
Sponsor
Louis Messina
Collaborators
BioMarin Pharmaceutical
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1. Study Identification

Unique Protocol Identification Number
NCT04800692
Brief Title
The Effects of ATLAS Therapy on Nitric Oxide Bioavailability in Patients With Intermittent Claudication
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 15, 2021 (Actual)
Primary Completion Date
July 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Louis Messina
Collaborators
BioMarin Pharmaceutical

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Claudication, Intermittent, Peripheral Artery Disease, Peripheral Vascular Diseases

7. Study Design

Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
All subjects will receive the same starting dose of the 3 components which will be escalated at day 45.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Tetrahydrobiopterin Dose 1 (Day 0 to 44)
Arm Type
Experimental
Arm Description
All subjects will receive 3300mg l-Ascorbate , l-Arginine 3400mg and 10mg/kg of Tetrahydrobiopterin once a day.
Arm Title
Tetrahydrobiopterin Dose 2 (Day 45 to 90)
Arm Type
Experimental
Arm Description
All subjects will receive 3300mg l-Ascorbate, l-Arginine 3400mg and 20mg/kg of Tetrahydrobiopterin once a day.
Intervention Type
Drug
Intervention Name(s)
Tetrahydrobiopterin 10 mg/kg
Other Intervention Name(s)
sapropterin, kuvan
Intervention Description
10mg/kg of Tetrahydrobiopterin daily.
Intervention Type
Drug
Intervention Name(s)
Tetrahydrobiopterin 20 mg/kg
Other Intervention Name(s)
sapropterin, kuvan
Intervention Description
20mg/kg of Tetrahydrobiopterin daily.
Intervention Type
Drug
Intervention Name(s)
L-Ascorbate
Intervention Description
3300 mg of l-ascorbate once daily
Intervention Type
Drug
Intervention Name(s)
L-Arginine
Intervention Description
3400mg of l-arginine once daily
Primary Outcome Measure Information:
Title
Nitric Oxide bioavailability
Description
Nitric Oxide bioavailability as measured by flow mediated dilatation (FMD).
Time Frame
90 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Shauneen Valliere, MSN
Phone
508-856-1767
Email
shauneen.valliere@umassmed.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Mollynda McArthur, MS
Phone
508-856-2820
Email
mollynda.mcarthur2@umassmed.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Louis M Messina, MD
Organizational Affiliation
UMASS Medical School
Official's Role
Principal Investigator
Facility Information:
Facility Name
UMASS Memorial Healthcare - University Campus
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shauneen Valliere, MSN
Phone
508-856-1767
Email
shauneen.valliere@umassmed.edu
First Name & Middle Initial & Last Name & Degree
Mollynda McArthur, MS
Phone
508-856-2820
Email
mollynda.mcarthur2@umassmed.edu

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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