Chelation Therapy in Diabetic Patients With Critical Limb Ischemia

The purpose of this research study is to evaluate the effect of ethylenediaminetetraacetic
acid (EDTA) based chelation therapy plus vitamins in diabetic patients with severe peripheral
artery disease presenting with impending amputation and determine if there is an improvement
in outcomes and a delay or reduction of amputations.

The investigators propose to enroll 10 patients in an open-label study of TACT-formula,
EDTA-based chelation therapy + commercially available TACT oral multi vitamins, delivering
40-50 infusions over 1 year. Clinical assessment, and noninvasive blood flow assessments will
be performed at baseline, and at completion of 20 and 40 infusions. HIPAA-compliant
photographs of the affected lower limbs will be taken at each infusion visit.

The specific aims of this open-label pilot study are to:

1. Assess the effect of EDTA-based chelation therapy plus vitamins in diabetic patients
with below-the-knee peripheral artery disease presenting with impending amputation and
determine if there is an improvement in vascular flow parameters, such that the
scheduled amputation can be averted or reduced in extent.

2. Co-primary severity endpoint: Changes in pain scores, quality of life, wound severity,
segmental lower extremity pressures and endothelial function.

3. Assess safety of EDTA-based chelation therapy in this patient population, defined as
deterioration of renal function, symptomatic hypocalcemia or hypoglycemia within 8 hours
of each infusion, or Class 4 heart failure within 24 hours of an infusion.

Inclusion Criteria:

- Male or female older than 50 years of age;

- On treatment for diabetes mellitus, or fasting glucose 126 mg/dL or higher, or
self-identified as diabetic

- Diagnostic of moderate or high-risk infra-popliteal chronic critical limb ischemia
(Rutherford Clinical Severity Score 4 or 5) defined as:

- The presence of rest pain or non-healing ulceration for at least 2 weeks plus:

- A resting ankle systolic pressure (in either the dorsalis pedis or posterior tibial
arteries) of ≤60 mmHg in the affected limb); or

- A resting toe systolic pressure of ≤40 mmHg in the affected limb or

- Skin perfusion pressure of ≤40 mmHg in the affected limb

- Significant stenosis (≥75%) of two or more infra-popliteal arteries in the affected
limb as verified by one imaging technique (angiography, magnetic resonance angiography
(MRA), computed tomographic angiography (CTA) or doppler examination) within 6 months
prior to enrollment;

- Patients able to give informed consent.

Exclusion Criteria:

- Arterial insufficiency or ulcer in the lower extremity as the result of a
non-atherosclerotic disorder.

- Subjects with evidence of active osteomyelitis or deep ulceration exposing bone or
tendon in the extremity planned for treatment;

- Subjects in whom there is extensive heel ulceration

- Intravenous chelation therapy within 1 year (>5 infusions)

- Allergy to any study drug

- Symptomatic or clinically evident heart failure

- Heart failure hospitalization within 6 months

- Blood pressure >160/100

- No venous access

- Serum creatinine >2.0 mg/dL

- Platelet count <100000/mm3

- Cigarette smoking within the last 3 months

- Liver disease or Alanine aminotransferase (ALT), aspartate aminotransferase (AST) >
2.0 times the upper limit of normal

- Diseases of copper, iron, or calcium metabolism

- Inability to tolerate the study-required fluid load

- Inability to keep to study schedules

- Medical condition likely to affect patient survival within 4 years

- Women of child-bearing potential