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

Study Overview
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Brief Summary
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In this pilot clinical study the investigators propose to conduct a prospective, randomized, double-blinded, placebo-controlled clinical trial for 30 days for participants with critical limb ischemia (CLI) who undergo a major (above-knee or below-knee) lower extremity amputation. By exploring the primary endpoints we aim to determine whether NAC can affect amputation stump perfusion and healing. Based on preclinical data, the investigators hypothesize that NAC will augment both amputation stump perfusion as well as healing. The investigators will utilize the data from this trial to determine the true effect size that is necessary for a larger clinical trial to determine the clinical efficacy of NAC is healing surgical sites such as major lower extremity amputation stumps.

Detailed Description
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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.

Official Title
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N-Acetyl-Cysteine for Healing of Amputation Stumps in the Setting of Diabetes

Conditions
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Diabetes Mellitus, Critical Limb Ischemia, Lower Limb Amputation Knee, Peripheral Arterial Disease

Intervention / Treatment
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* Drug: Active Arm N-acetyl cysteine (NAC)
* Drug: Placebo Arm


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Arm N-acetyl cysteine (NAC)<br>Upon study enrollment, patients will be randomized 1:1 by Investigational Pharmacy to a standard adult intravenous dose of NAC (1200mg twice a day) for 6 days post-amputation. | Drug: Active Arm N-acetyl cysteine (NAC)<br>* N-acetyl cysteine (NAC) 1200mg twice a day for 6 days post-amputation<br>* Other names: N-acetyl cysteine (NAC);|
| Placebo Comparator: Placebo Arm<br>Upon study enrollment, patients will be randomized 1:1 by Investigational Pharmacy to placebo ½ normal saline infusion (twice a day) for 6 days post-amputation. | Drug: Placebo Arm<br>* Placebo 1/2 normal saline infusion twice a day for 6 days post-amputation<br>* Other names: Placebo 1/2 normal saline infusion;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stump Healing using the Bates-Jensen Wound Assessment Tool | A validated scoring algorithm used to determine the degree to which a wound has successfully healed. We will use a modified version of this tool and score the following parameters: amputation stump skin color, epithelialization, amount and type of exudate, and the size and type of necrotic eschar tissue. Each feature was evaluated on a 1 through 5 scoring system, with lower scores indicating best healing, and higher scores indicating poor healing. Participants are given an overall aggregate score, with higher scores indicating poor healing. These measurements are taken at the participant's first clinical follow up appointment. | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine effect size to power a larger trial | Statistical measurement of effect size to power a larger trial. | 1 year |