The Effects of ATLAS (Arginine Tetrahydrobiopterin L-Ascorbate) Therapy on Nitric Oxide Bioavailability and Pain-free Walking in Patients With Intermittent Claudication
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Nitric Oxide bioavailability
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: L-Ascorbate (Drug)
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.
干预措施: Tetrahydrobiopterin 10 mg/kg (Drug)
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.
干预措施: Tetrahydrobiopterin 20 mg/kg (Drug)
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.
干预措施: L-Arginine (Drug)
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.
干预措施: L-Arginine (Drug)
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.
干预措施: L-Ascorbate (Drug)
结局指标
主要结局
Nitric Oxide bioavailability
时间窗: 90 days
Nitric Oxide bioavailability as measured by flow mediated dilatation (FMD).
次要结局
未报告次要终点
研究者
Louis Messina
Professor
University of Massachusetts, Worcester