<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03253328</url>
  </required_header>
  <id_info>
    <org_study_id>201611065</org_study_id>
    <nct_id>NCT03253328</nct_id>
  </id_info>
  <brief_title>N-Acetyl-Cysteine (NAC) for Healing of Amputation Stumps in the Setting of Diabetes</brief_title>
  <official_title>N-Acetyl-Cysteine for Healing of Amputation Stumps in the Setting of Diabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Washington University School of Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this pilot clinical study the investigators propose to conduct a prospective, randomized,&#xD;
      double-blinded, placebo-controlled clinical trial for 30 days for participants with critical&#xD;
      limb ischemia (CLI) who undergo a major (above-knee or below-knee) lower extremity&#xD;
      amputation. By exploring the primary endpoints we aim to determine whether NAC can affect&#xD;
      amputation stump perfusion and healing. Based on preclinical data, the investigators&#xD;
      hypothesize that NAC will augment both amputation stump perfusion as well as healing. The&#xD;
      investigators will utilize the data from this trial to determine the true effect size that is&#xD;
      necessary for a larger clinical trial to determine the clinical efficacy of NAC is healing&#xD;
      surgical sites such as major lower extremity amputation stumps.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this pilot clinical study the investigators propose to conduct a prospective, randomized,&#xD;
      double-blinded, placebo-controlled clinical trial, in 50 participants with CLI who have&#xD;
      undergone a major (above-knee or below-knee) lower extremity amputation. 25 participants will&#xD;
      receive NAC 1200mg intravenously twice a day for 6 consecutive days following amputation. 25&#xD;
      participants will receive placebo saline intravenous infusion twice a day for 6 days&#xD;
      following amputation. Post-amputation participants will be monitored for specific&#xD;
      anthropometric parameters and stump perfusion assessments (using laser-assisted fluorescent&#xD;
      angiography and transcutaneous oxygen pressure measurement). The primary study endpoints are&#xD;
      to determine if lower extremity stump healing and perfusion are affected by perioperative NAC&#xD;
      administration. A secondary endpoint will be to determine the effect size that would be&#xD;
      necessary to power a larger clinical trial to determine whether NAC treatment can affect&#xD;
      tissue perfusion and healing at major lower extremity amputation stumps in participants with&#xD;
      CLI.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Suspended</overall_status>
  <why_stopped>
    No one is currently receiving treatment and enrollment is of course on hold. Subjects being&#xD;
    unblinded to perform interim analysis.&#xD;
  </why_stopped>
  <start_date type="Actual">December 15, 2016</start_date>
  <completion_date type="Anticipated">August 31, 2022</completion_date>
  <primary_completion_date type="Actual">August 31, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Stump Healing using the Bates-Jensen Wound Assessment Tool</measure>
    <time_frame>30 days</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Determine effect size to power a larger trial</measure>
    <time_frame>1 year</time_frame>
    <description>Statistical measurement of effect size to power a larger trial.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Perfusion</measure>
    <time_frame>30 days</time_frame>
    <description>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.</description>
  </other_outcome>
  <other_outcome>
    <measure>Stump Healing</measure>
    <time_frame>5 days</time_frame>
    <description>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.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Diabetes Mellitus</condition>
  <condition>Critical Limb Ischemia</condition>
  <condition>Lower Limb Amputation Knee</condition>
  <condition>Peripheral Arterial Disease</condition>
  <arm_group>
    <arm_group_label>Active Arm N-acetyl cysteine (NAC)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Arm</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Active Arm N-acetyl cysteine (NAC)</intervention_name>
    <description>N-acetyl cysteine (NAC) 1200mg twice a day for 6 days post-amputation</description>
    <arm_group_label>Active Arm N-acetyl cysteine (NAC)</arm_group_label>
    <other_name>N-acetyl cysteine (NAC)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Arm</intervention_name>
    <description>Placebo 1/2 normal saline infusion twice a day for 6 days post-amputation</description>
    <arm_group_label>Placebo Arm</arm_group_label>
    <other_name>Placebo 1/2 normal saline infusion</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject undergoing elective major (above-knee or below-knee) lower extremity&#xD;
             amputation for CLI&#xD;
&#xD;
          -  Both male and female patients&#xD;
&#xD;
          -  All ethnic groups&#xD;
&#xD;
          -  Between of the ages of 30-90 years old&#xD;
&#xD;
          -  Adequate nutritional status - defined as BMI &gt; 19&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant women, and women who are breastfeeding&#xD;
&#xD;
          -  Known history of end-stage liver disease&#xD;
&#xD;
          -  Severe asthma&#xD;
&#xD;
          -  Heavy alcohol consumption (male &gt; 2 drinks per day and women &gt; 1 drink per day)&#xD;
&#xD;
          -  Individuals actively receiving chemotherapy.&#xD;
&#xD;
          -  Anticipated enrollment in another study that investigates another drug agent within 30&#xD;
             days from enrollment in this study.&#xD;
&#xD;
          -  Patients receiving carbamazepine.&#xD;
&#xD;
          -  Severe anemia (HCT &lt; 22).&#xD;
&#xD;
          -  Allergy to either NAC or Indocyanine Green (ICG).&#xD;
&#xD;
          -  Patients with open wound(s) from a prior amputation on the ipsilateral limb (excluding&#xD;
             patients who had prior partial foot amputation, who are now requiring a below-knee or&#xD;
             above-knee amputation).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mohamed Zayed, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>March 17, 2017</study_first_submitted>
  <study_first_submitted_qc>August 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 17, 2017</study_first_posted>
  <last_update_submitted>April 11, 2022</last_update_submitted>
  <last_update_submitted_qc>April 11, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Peripheral Arterial Disease</mesh_term>
    <mesh_term>Peripheral Vascular Diseases</mesh_term>
    <mesh_term>Chronic Limb-Threatening Ischemia</mesh_term>
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Ischemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acetylcysteine</mesh_term>
    <mesh_term>N-monoacetylcystine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>June 21, 2022</submitted>
    <submission_canceled>June 22, 2022</submission_canceled>
    <submitted>June 27, 2022</submitted>
    <returned>July 21, 2022</returned>
    <submitted>August 2, 2022</submitted>
    <returned>June 29, 2023</returned>
    <submitted>July 14, 2023</submitted>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03253328
org study id: 201611065
nct id: NCT03253328
lead sponsor: 
has dmc: Yes
is fda regulated device: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Stump Healing using the Bates-Jensen Wound Assessment Tool
time frame: 30 days
description: 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.
measure: Determine effect size to power a larger trial
time frame: 1 year
description: Statistical measurement of effect size to power a larger trial.
measure: Perfusion
time frame: 30 days
description: 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.
measure: Stump Healing
time frame: 5 days
description: 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.
arm group label: Active Arm N-acetyl cysteine (NAC)
arm group type: Active Comparator
description: 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.
arm group label: Placebo Arm
arm group type: Placebo Comparator
description: 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.
intervention type: Drug
intervention name: Active Arm N-acetyl cysteine (NAC)
description: N-acetyl cysteine (NAC) 1200mg twice a day for 6 days post-amputation
arm group label: Active Arm N-acetyl cysteine (NAC)
other name: N-acetyl cysteine (NAC)
intervention type: Drug
intervention name: Placebo Arm
description: Placebo 1/2 normal saline infusion twice a day for 6 days post-amputation
arm group label: Placebo Arm
other name: Placebo 1/2 normal saline infusion
criteria: 
gender: All
minimum age: 30 Years
maximum age: 90 Years
healthy volunteers: No
last name: Mohamed Zayed, MD
role: Principal Investigator
affiliation: Washington University School of Medicine
facility: 
country: United States
responsible party type: Sponsor
mesh term: Peripheral Arterial Disease
mesh term: Peripheral Vascular Diseases
mesh term: Chronic Limb-Threatening Ischemia
mesh term: Diabetes Mellitus
mesh term: Ischemia
mesh term: Acetylcysteine
mesh term: N-monoacetylcystine
sharing ipd: No
submitted: June 21, 2022
submission canceled: June 22, 2022
submitted: June 27, 2022
returned: July 21, 2022
submitted: August 2, 2022
returned: June 29, 2023
submitted: July 14, 2023