N-Acetyl-Cysteine (NAC) for Healing of Amputation Stumps in the Setting of Diabetes

In this pilot clinical study the investigators propose to conduct a prospective, randomized,
double-blinded, placebo-controlled clinical trial, in 50 participants with CLI who have
undergone a major (above-knee or below-knee) lower extremity amputation. 25 participants will
receive NAC 1200mg intravenously twice a day for 6 consecutive days following amputation. 25
participants will receive placebo saline intravenous infusion twice a day for 6 days
following amputation. Post-amputation participants will be monitored for specific
anthropometric parameters and stump perfusion assessments (using laser-assisted fluorescent
angiography and transcutaneous oxygen pressure measurement). The primary study endpoints are
to determine if lower extremity stump healing and perfusion are affected by perioperative NAC
administration. A secondary endpoint will be to determine the effect size that would be
necessary to power a larger clinical trial to determine whether NAC treatment can affect
tissue perfusion and healing at major lower extremity amputation stumps in participants with
CLI.

Inclusion Criteria:

- Subject undergoing elective major (above-knee or below-knee) lower extremity
amputation for CLI

- Both male and female patients

- All ethnic groups

- Between of the ages of 30-90 years old

- Adequate nutritional status - defined as BMI > 19

Exclusion Criteria:

- Pregnant women, and women who are breastfeeding

- Known history of end-stage liver disease

- Severe asthma

- Heavy alcohol consumption (male > 2 drinks per day and women > 1 drink per day)

- Individuals actively receiving chemotherapy.

- Anticipated enrollment in another study that investigates another drug agent within 30
days from enrollment in this study.

- Patients receiving carbamazepine.

- Severe anemia (HCT < 22).

- Allergy to either NAC or Indocyanine Green (ICG).

- Patients with open wound(s) from a prior amputation on the ipsilateral limb (excluding
patients who had prior partial foot amputation, who are now requiring a below-knee or
above-knee amputation).