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

ID: NCT03253328
Status: Recruiting
Phase: N/A
Start Date: December 15, 2016
First Submitted: March 17, 2017
Last Updated: February 19, 2018
Results: N/A
Sponsors & Collaborators: Washington University School of Medicine
Location: United States
Conditions: Diabetes Mellitus, Critical Limb Ischemia, Lower Limb Amputation Knee, Peripheral Arterial Disease
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.

Study Description

Brief Summary

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

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.
Condition or disease Intervention/treatment Phase

Critical Limb Ischemia

Diabetes Mellitus

Lower Limb Amputation Knee

Peripheral Arterial Disease

Drug: Active Arm N-acetyl cysteine (NAC)
Other Names
N-acetyl cysteine (NAC)
Drug: Placebo Arm
Other Names
Placebo 1/2 normal saline infusion
N/A

Tracking Information

First Submitted DateMarch 17, 2017
Last Update Posted DateFebruary 19, 2018
Actual Start DateDecember 15, 2016
Anticipated Completion DateDecember 31, 2018
Actual Primary Completion DateDecember 31, 2018
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Stump Healing using the Bates-Jensen Wound Assessment Tool [Time Frame: 30 days]

    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.

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Determine effect size to power a larger trial [Time Frame: 1 year]

    Statistical measurement of effect size to power a larger trial.

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleN-Acetyl-Cysteine (NAC) for Healing of Amputation Stumps in the Setting of Diabetes
Official TitleN-Acetyl-Cysteine for Healing of Amputation Stumps in the Setting of Diabetes
Brief Summary

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

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.

Study TypeInterventional
Study PhaseN/A
Estimated Enrollment
50
Allocation
Randomized
Interventional Model
Parallel Assignment
Masking
Quadruple
Primary Purpose
Treatment
Conditions
Critical Limb Ischemia
Diabetes Mellitus
Lower Limb Amputation Knee
Peripheral Arterial Disease
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: Active Arm N-acetyl cysteine (NAC)

N-acetyl cysteine (NAC) 1200mg twice a day for 6 days post-amputation

Other Names
N-acetyl cysteine (NAC)
Drug: Placebo Arm

Placebo 1/2 normal saline infusion twice a day for 6 days post-amputation

Other Names
Placebo 1/2 normal saline infusion
Study Groups/Cohorts
Active Arm N-acetyl cysteine (NAC)
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.

Placebo Arm
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.

Study Arms
Active Comparator Active Arm N-acetyl cysteine (NAC)
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)
N-acetyl cysteine (NAC) 1200mg twice a day for 6 days post-amputation

Placebo Comparator Placebo Arm
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
Placebo 1/2 normal saline infusion twice a day for 6 days post-amputation

Arm Intervention/Treatment
Active Comparator Active Arm N-acetyl cysteine (NAC)
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)
Placebo Comparator Placebo Arm
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

Recruitment Information

Recruitment Status:Recruiting
Enrollment50
Completion DateDecember 31, 2018
Eligibility Criteria: 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).
GenderAll
Age30 Years to 90 Years
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
United States

Administrative Information

NCT Number:NCT03253328
Other Study ID Numbers
201611065
Has Data Monitoring CommitteeYes
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Washington University School of Medicine
Collaborators
Not Available
Investigators
Principal Investigator
Mohamed Zayed, MD
Washington University School of Medicine