The Effect of Donepezil on Wound Healing

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.

Study Overview

• Status: Recruiting
• Conditions: Wound Heal
• Intervention / Treatment: Drug: Placebo oral tablet; Drug: Donepezil; Drug: Topical Zinc Oxide

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Easton, Maryland, United States, 21601
      • Recruiting
      • University of Maryland Shore Medical Center at Easton
      • Contact: Stephen Wills, MD; Phone Number: 410-822-1000; Email: swills@umm.edu
      • Principal Investigator: Stephen Wills, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• over the age of 20
• diagnosed with Diabetes Mellitus

Exclusion Criteria:

• under the age of 20
• pregnant of lactating
• lactose intolerance
• allergy to donepezil
• prothrombin time and international normalized ratio value greater than 1.25
• Pre Menopausal women/ Women of childbearing potential

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Donepezil and Topical Zinc Oxide; donepezil 5mg daily and topical zinc oxide 20% three times daily	Drug: Donepezil; donepezil orally 5mg; Drug: Topical Zinc Oxide; Topical Zinc Oxide 20%
Placebo Comparator: Placebo and Topical Zinc Oxide; Placebo daily and topical zinc oxide 20% three times daily	Drug: Placebo oral tablet; Placebo; Drug: Topical Zinc Oxide; Topical Zinc Oxide 20%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in depth wound	Wound will be measured in centimeters and assessed for change.	2-4 weeks
Change in diameter of the wound	Wound will be measured in centimeters and assessed for change.	2-4 weeks

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2020
• Primary Completion (Anticipated): July 30, 2023
• Study Completion (Anticipated): July 30, 2023

Study Registration Dates

• First Submitted: March 5, 2020
• First Submitted That Met QC Criteria: August 6, 2020
• First Posted (Actual): August 10, 2020

Study Record Updates

• Last Update Posted (Actual): May 22, 2023
• Last Update Submitted That Met QC Criteria: May 19, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Protective Agents; Dermatologic Agents; Nootropic Agents; Radiation-Protective Agents; Cholinesterase Inhibitors; Sunscreening Agents; Donepezil; Zinc Oxide
• Other Study ID Numbers: SH2019-8

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No