<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/NCT04505670</url>
  </required_header>
  <id_info>
    <org_study_id>SH2019-8</org_study_id>
    <nct_id>NCT04505670</nct_id>
  </id_info>
  <brief_title>The Effect of Donepezil on Wound Healing</brief_title>
  <official_title>The Effect of Donepezil on Wound Healing</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Maryland, Baltimore</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Maryland, Baltimore</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to test effectiveness of donepezil to improve wound healing in&#xD;
      patients with diabetic wounds that have not healed with standard treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will be a randomized double blind study whereby patients with refractory diabetic&#xD;
      wound healing over 3-6 months will be randomized to ascertain the effect of donepezil&#xD;
      (administration of 5 mg to 10 mg of donepezil daily, orally, over 6 week period) on clinical&#xD;
      wound healing reflecting correction of diabetic microvascular disease of non-healing wounds.&#xD;
      The subjects will be recruited from the University of Maryland Shore Medical Center at&#xD;
      Easton's emergency room and inpatients. Subjects will also be recruited from University of&#xD;
      Maryland Shore Medical Group Wound Care and University of Maryland Baltimore Washington&#xD;
      Medical Center's Vascular Clinic.&#xD;
&#xD;
      20 patients with Type 2 Diabetes Mellitus (Adult Onset Diabetes Mellitus) and non-healing&#xD;
      ulcers/ wounds refractory to management with topical preparation and local debridement over a&#xD;
      3 to 6 month period prior will randomized to treatment or control group. The study group will&#xD;
      be treated with oral donepezil (5 to 10 mg ). After 3 days of treatment, the dose of&#xD;
      donepezil or placebo will be increased to 10 if no improvements are noted in skin integrity&#xD;
      in the feet or lower extremity. Improvements in capillary refill and vascular edema will&#xD;
      determine increase of donepezil from 5 to 10 mg. All patients will receive topical zinc oxide&#xD;
      20% topically three times a day, an effective topical management of diabetic wounds.&#xD;
      Measurement of wound size and depth will be made prior to treatment. Additionally a color&#xD;
      photograph will be obtained to compare with wound appearance in 6 weeks.&#xD;
&#xD;
      As many patients as required to meet the enrollment numbers shall be screened. Patients will&#xD;
      be monitored daily for blood pressure, glucose levels and heart rate, during the period of&#xD;
      hospitalization. Adjustments in insulin or oral hypoglycemic, blood pressure and heart rate&#xD;
      control medications will occur during this time. Follow up visits will be made as required&#xD;
      and at the end of week 6.&#xD;
&#xD;
      Donepezil shall be orally administered to the study group. Control group will get an orally&#xD;
      administered placebo which is an inert compound, lactulose.&#xD;
&#xD;
      Wk0 will be the randomization visit. The patients will take the drug for 6 weeks and the last&#xD;
      follow up visit will be the last day of week 6. Follow up at 6 weeks will occur at Shore&#xD;
      Rehab at Easton.&#xD;
&#xD;
      Any anticholinergic drugs will be eliminated from the patients' medical regimen with the&#xD;
      exception for inhaled anticholinergic. There is no known major contraindication of&#xD;
      acetylcholinesterase inhibitors (like for eg: galantamine, rivastigmine and donepezil)&#xD;
      Patients shall be monitored closely for vagotonic effect. Acetylcholine is known to have a&#xD;
      vagotonic effect lowering heart rate and blood pressure. Therefore, during the course of&#xD;
      administration of the drug close attention to heart rate and blood pressure will be a&#xD;
      significant part off the clinical management of patients. If the patients are on beta&#xD;
      blockers, their beta blocker dose will be closely monitored and adjusted as required.&#xD;
&#xD;
      H2 antagonist will be used to guard against any possible GI bleed, Pepcid 20mg a day.&#xD;
&#xD;
      Patient will be observed for seizures. The patients will be examined for pulmonary&#xD;
      exacerbation during treatment in the hospital. If the pulmonary status deteriorates they will&#xD;
      be eliminated from the study. The medication administration will not start sooner than 24 hrs&#xD;
      after surgery. Patients shall be observed for exaggerated response from anesthesia.&#xD;
&#xD;
      Photographs of the diabetic wound/ ulcer and HgbA1C will be obtained on introduction to study&#xD;
      and obtained at completion at 6 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 30, 2020</start_date>
  <completion_date type="Anticipated">July 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">July 30, 2023</primary_completion_date>
  <phase>Phase 2</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in depth wound</measure>
    <time_frame>2-4 weeks</time_frame>
    <description>Wound will be measured in centimeters and assessed for change.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in diameter of the wound</measure>
    <time_frame>2-4 weeks</time_frame>
    <description>Wound will be measured in centimeters and assessed for change.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Wound Heal</condition>
  <arm_group>
    <arm_group_label>Donepezil and Topical Zinc Oxide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>donepezil 5mg daily and topical zinc oxide 20% three times daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo and Topical Zinc Oxide</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo daily and topical zinc oxide 20% three times daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Donepezil</intervention_name>
    <description>donepezil orally 5mg</description>
    <arm_group_label>Donepezil and Topical Zinc Oxide</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo oral tablet</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Placebo and Topical Zinc Oxide</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Topical Zinc Oxide</intervention_name>
    <description>Topical Zinc Oxide 20%</description>
    <arm_group_label>Donepezil and Topical Zinc Oxide</arm_group_label>
    <arm_group_label>Placebo and Topical Zinc Oxide</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  over the age of 20&#xD;
&#xD;
          -  diagnosed with Diabetes Mellitus&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  under the age of 20&#xD;
&#xD;
          -  pregnant of lactating&#xD;
&#xD;
          -  lactose intolerance&#xD;
&#xD;
          -  allergy to donepezil&#xD;
&#xD;
          -  prothrombin time and international normalized ratio value greater than 1.25&#xD;
&#xD;
          -  Pre Menopausal women/ Women of childbearing potential&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Maryland Shore Medical Center at Easton</name>
      <address>
        <city>Easton</city>
        <state>Maryland</state>
        <zip>21601</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Stephen Wills, MD</last_name>
      <phone>410-822-1000</phone>
      <email>swills@umm.edu</email>
    </contact>
    <investigator>
      <last_name>Stephen Wills, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>March 5, 2020</study_first_submitted>
  <study_first_submitted_qc>August 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2020</study_first_posted>
  <last_update_submitted>May 19, 2023</last_update_submitted>
  <last_update_submitted_qc>May 19, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Maryland, Baltimore</investigator_affiliation>
    <investigator_full_name>Stephen Wills</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Donepezil</mesh_term>
    <mesh_term>Zinc Oxide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04505670
org study id: SH2019-8
nct id: NCT04505670
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
The purpose of the study is to test effectiveness of donepezil to improve wound healing in
      patients with diabetic wounds that have not healed with standard treatment.
The study will be a randomized double blind study whereby patients with refractory diabetic
      wound healing over 3-6 months will be randomized to ascertain the effect of donepezil
      (administration of 5 mg to 10 mg of donepezil daily, orally, over 6 week period) on clinical
      wound healing reflecting correction of diabetic microvascular disease of non-healing wounds.
      The subjects will be recruited from the University of Maryland Shore Medical Center at
      Easton's emergency room and inpatients. Subjects will also be recruited from University of
      Maryland Shore Medical Group Wound Care and University of Maryland Baltimore Washington
      Medical Center's Vascular Clinic.

      20 patients with Type 2 Diabetes Mellitus (Adult Onset Diabetes Mellitus) and non-healing
      ulcers/ wounds refractory to management with topical preparation and local debridement over a
      3 to 6 month period prior will randomized to treatment or control group. The study group will
      be treated with oral donepezil (5 to 10 mg ). After 3 days of treatment, the dose of
      donepezil or placebo will be increased to 10 if no improvements are noted in skin integrity
      in the feet or lower extremity. Improvements in capillary refill and vascular edema will
      determine increase of donepezil from 5 to 10 mg. All patients will receive topical zinc oxide
      20% topically three times a day, an effective topical management of diabetic wounds.
      Measurement of wound size and depth will be made prior to treatment. Additionally a color
      photograph will be obtained to compare with wound appearance in 6 weeks.

      As many patients as required to meet the enrollment numbers shall be screened. Patients will
      be monitored daily for blood pressure, glucose levels and heart rate, during the period of
      hospitalization. Adjustments in insulin or oral hypoglycemic, blood pressure and heart rate
      control medications will occur during this time. Follow up visits will be made as required
      and at the end of week 6.

      Donepezil shall be orally administered to the study group. Control group will get an orally
      administered placebo which is an inert compound, lactulose.

      Wk0 will be the randomization visit. The patients will take the drug for 6 weeks and the last
      follow up visit will be the last day of week 6. Follow up at 6 weeks will occur at Shore
      Rehab at Easton.

      Any anticholinergic drugs will be eliminated from the patients' medical regimen with the
      exception for inhaled anticholinergic. There is no known major contraindication of
      acetylcholinesterase inhibitors (like for eg: galantamine, rivastigmine and donepezil)
      Patients shall be monitored closely for vagotonic effect. Acetylcholine is known to have a
      vagotonic effect lowering heart rate and blood pressure. Therefore, during the course of
      administration of the drug close attention to heart rate and blood pressure will be a
      significant part off the clinical management of patients. If the patients are on beta
      blockers, their beta blocker dose will be closely monitored and adjusted as required.

      H2 antagonist will be used to guard against any possible GI bleed, Pepcid 20mg a day.

      Patient will be observed for seizures. The patients will be examined for pulmonary
      exacerbation during treatment in the hospital. If the pulmonary status deteriorates they will
      be eliminated from the study. The medication administration will not start sooner than 24 hrs
      after surgery. Patients shall be observed for exaggerated response from anesthesia.

      Photographs of the diabetic wound/ ulcer and HgbA1C will be obtained on introduction to study
      and obtained at completion at 6 weeks.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Change in depth wound
time frame: 2-4 weeks
description: Wound will be measured in centimeters and assessed for change.
measure: Change in diameter of the wound
time frame: 2-4 weeks
description: Wound will be measured in centimeters and assessed for change.
arm group label: Donepezil and Topical Zinc Oxide
arm group type: Experimental
description: donepezil 5mg daily and topical zinc oxide 20% three times daily
arm group label: Placebo and Topical Zinc Oxide
arm group type: Placebo Comparator
description: Placebo daily and topical zinc oxide 20% three times daily
intervention type: Drug
intervention name: Donepezil
description: donepezil orally 5mg
arm group label: Donepezil and Topical Zinc Oxide
intervention type: Drug
intervention name: Placebo oral tablet
description: Placebo
arm group label: Placebo and Topical Zinc Oxide
intervention type: Drug
intervention name: Topical Zinc Oxide
description: Topical Zinc Oxide 20%
arm group label: Donepezil and Topical Zinc Oxide
arm group label: Placebo and Topical Zinc Oxide
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Maryland, Baltimore
investigator full name: Stephen Wills
investigator title: Principal Investigator
mesh term: Wounds and Injuries
mesh term: Donepezil
mesh term: Zinc Oxide
sharing ipd: No