Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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.
ClinicalTrials.gov Identifier: NCT03253328
Recruitment Status : Recruiting
First Posted : August 17, 2017
Last Update Posted : March 28, 2019
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine

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.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus Critical Limb Ischemia Lower Limb Amputation Knee Peripheral Arterial Disease Drug: Active Arm N-acetyl cysteine (NAC) Drug: Placebo Arm Not Applicable

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: N-Acetyl-Cysteine for Healing of Amputation Stumps in the Setting of Diabetes
Actual Study Start Date : December 15, 2016
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine


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)
N-acetyl cysteine (NAC) 1200mg twice a day for 6 days post-amputation
Other Name: 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
Placebo 1/2 normal saline infusion twice a day for 6 days post-amputation
Other Name: Placebo 1/2 normal saline infusion




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Determine effect size to power a larger trial [ Time Frame: 1 year ]
    Statistical measurement of effect size to power a larger trial.


Other Outcome Measures:
  1. Perfusion [ Time Frame: 30 days ]
    The Primary Study Endpoints will measure if patients who receive peri-operative NAC administrative have lower Bates-Jensen Wound Healing Scores than their non-NAC counterparts.

  2. Stump Healing [ Time Frame: 5 days ]
    The Primary Study Endpoints will measure if patients who receive peri-operative NAC administrative have lower Bates-Jensen Wound Healing Scores than their non-NAC counterparts.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   30 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03253328


Contacts
Layout table for location contacts
Contact: Mohamed Zayed, MD 314-362-5648 zayedm@wustl.edu
Contact: Ashley Burgess, RN (314) 3626257 Ashley.burgett@wustl.edu

Locations
Layout table for location information
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Mohamed Zayed, M.D.    314-362-5648    zayedm@wustl.edu   
Principal Investigator: Mohamed Zayed, M.D.         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Layout table for investigator information
Principal Investigator: Mohamed Zayed, MD Washington University School of Medicine

Layout table for additonal information
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT03253328     History of Changes
Other Study ID Numbers: 201611065
First Posted: August 17, 2017    Key Record Dates
Last Update Posted: March 28, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Diabetes Mellitus
Ischemia
Peripheral Arterial Disease
Peripheral Vascular Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pathologic Processes
Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Acetylcysteine
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes