Donepezil Compared to Placebo in Patients With Chronic Neuropathic Pain

• ClinicalTrials.gov Identifier: NCT01743976
• Recruitment Status: Terminated
• First Posted: December 6, 2012
• Results First Posted: November 18, 2020
• Last Update Posted: March 2, 2021
• Sponsor: Wake Forest University
• Collaborator: National Institute of Neurological Disorders and Stroke (NINDS)
• Information provided by (Responsible Party): Wake Forest University Health Sciences ( Wake Forest University )

Tracking Information

• First Submitted Date: November 20, 2012
• First Posted Date: December 6, 2012
• Results First Submitted Date: September 22, 2020
• Results First Posted Date: November 18, 2020
• Last Update Posted Date: March 2, 2021
• Actual Study Start Date: December 2012
• Actual Primary Completion Date: October 23, 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 5, 2021)

• McGill Short Form Pain Questionnaire (SF MPQ) Visual Analog Scale (VAS) Pain Intensity [ Time Frame: baseline ]
  A greater number is considered a worse outcome. VAS Range (0-10) 0=No Pain 10=The worst pain imaginable.
• McGill Short Form Pain Questionnaire (SF MPQ) Visual Analog Scale (VAS) Pain Intensity [ Time Frame: Week 8: last week of study drug treatment ]
  A greater number is considered a worse outcome. VAS Range (0-10) 0=No Pain 10=The worst pain imaginable.
• McGill Short Form Pain Questionnaire (SF MPQ) Visual Analog Scale (VAS) Pain Intensity [ Time Frame: Week 10: last week of washout ]
  A greater number is considered a worse outcome. VAS Range (0-10) 0=No Pain 10=The worst pain imaginable.

Original Primary Outcome Measures (submitted: December 4, 2012)

Pain Intensity [ Time Frame: 10 weeks ]

McGill short form pain questionnaire (SF MPQ)will be completed twice daily during the following time points: 2 weeks before taking study medication, 6 weeks during study medication, and 2 weeks after discontinuation of study medication. The visual analog scale (VAS) pain rating will serve as the study's primary outcome measure.

Current Secondary Outcome Measures (submitted: November 10, 2020)

• Average From Baseline Profile of Mood States-Short Form (POMS-SF) at 10 Weeks [ Time Frame: baseline, week 8 after baseline, and week 10 after baseline ]
  The questionnaire records total mood disturbance. The scale ranges from 0-100 with a greater number denoting a worse outcome.
• Number of Days With Rescue Treatment [ Time Frame: Days: baseline, week 8 after baseline, and week 10 after baseline ]
  Questionnaires detailing the amount of rescue pain medications will be completed twice daily.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: December 4, 2012)

• Change from baseline disability measures at 10 weeks [ Time Frame: 10 weeks ]
  The McGill short form pain questionnaire (SF MPQ) and the Profile of Mood States-Short Form (POMS-SF) will be completed twice daily during the following time points: 2 weeks before taking study medication, 6 weeks during study medication, and 2 weeks after discontinuation of study medication. Outcome responses from the questionnaires will be examined using General Linear Models (GLM), examining for differences in group either at one time period or as a function of study phase, as appropriate.
• Change from baseline psychometric measures at 10 weeks [ Time Frame: 10 weeks ]
  The Profile of Mood States-Short Form (POMS-SF) will be completed twice daily during the following time points: 2 weeks before taking study medication, 6 weeks during study medication, and 2 weeks after discontinuation of study medication. Outcome responses from the questionnaires will be examined using General Linear Models (GLM), examining for differences in group either at one time period or as a function of study phase, as appropriate.
• Change from baseline global assessments at 10 weeks [ Time Frame: 10 weeks ]
  The McGill short form pain questionnaire (SF MPQ) and the Profile of Mood States-Short Form (POMS-SF) will be completed twice daily during the following time points: 2 weeks before taking study medication, 6 weeks during study medication, and 2 weeks after discontinuation of study medication. Outcome responses from the questionnaires will be examined using General Linear Models (GLM), examining for differences in group either at one time period or as a function of study phase, as appropriate.
• Change from baseline rescue medication use at 10 weeks [ Time Frame: 10 weeks ]
  Questionnaires detailing the amount of rescue pain medications will be completed twice daily during the following time points: 2 weeks before taking study medication, 6 weeks during study medication, and 2 weeks after discontinuation of study medication. Outcome responses from the questionnaires will be examined using General Linear Models (GLM), examining for differences in group either at one time period or as a function of study phase, as appropriate.

Descriptive Information

• Brief Title: Donepezil Compared to Placebo in Patients With Chronic Neuropathic Pain
• Official Title: Donepezil Compared to Placebo in Patients With Chronic Neuropathic Pain
• Brief Summary: Based on laboratory studies, donepezil will improve pain relief more than placebo in patients with chronic neuropathic pain who are currently taking gabapentin or pregabalin.

Detailed Description

Investigators are currently examining in the laboratory the mechanisms which lead to sprouting of noradrenergic fibers in the spinal cord in models of chronic pain as well as the mechanisms that lead to a novel noradrenergic - cholinergic circuit in the spinal cord. In addition to examining the circumstances which generate this increased capacity for analgesia and the mechanisms by which they occur, investigators will test in this protocol whether approved and experimental treatments for neuropathic pain exploit this increased capacity.

This study is in patients with neuropathic pain taking gabapentin or pregabalin, and will test the clinical relevance of these preclinical data by comparing placebo to the cholinesterase inhibitor. Investigators focus not only on mechanistic hypotheses in the laboratory studies, but also on practical applications, using clinically approved drugs, including gabapentin and pregabalin to activate noradrenergic activity and donepezil (Aricept®), approved for the treatment of Alzheimer's dementia, but not previously tested to treat neuropathic pain, to inhibit cholinesterase. Each of these drugs may act by mechanisms in addition to those involved in descending noradrenergic inhibition, but investigators hypothesize that the therapeutic strength of their combination relies heavily on this cascade engendered by noradrenergic sprouting and altered α2-adrenoceptor function. The proposed studies will provide critical tests of this hypothesis and critical information to guide more effective clinical therapy of neuropathic pain.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Neuropathic Pain

Intervention

• Drug: Donepezil
  donepezil 5 mg once daily for 6 weeks
  Other Name: Aricept
• Drug: Placebo
  placebo or sugar pill will be taken once daily for 6 weeks
  Other Name: sugar pill

Study Arms

• Experimental: Donepezil
  donepezil 5 mg every day
  Intervention: Drug: Donepezil
• Placebo Comparator: Placebo
  Placebo (sugar pill) every day
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: September 9, 2020): 5
• Original Estimated Enrollment (submitted: December 4, 2012): 33
• Actual Study Completion Date: October 23, 2013
• Actual Primary Completion Date: October 23, 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Diagnosis of diabetic neuropathy or failed back syndrome with neuropathic symptoms
• Age 18-80
• Taking a stable dose of gabapentin or pregabalin

Exclusion Criteria:

• Pregnant women or women of child-bearing potential not willing to practice a reliable form of birth control
• Allergy to donepezil or other piperidine derivatives (including fentanyl, alfentanil, sulfentanil, remifentanyl, demerol, tramadol, loperamide, diphenoxylate, betaprodine, alphaprodine, ethopropazine, anileridine, piminodine, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP),loratadine, fexofenadine
• Unstable medical conditions including cardiac, pulmonary, renal or hepatic diseases that, in the opinion of the investigator, would preclude patients from finishing the trial
• Any person with pending litigation
• A history of major psychosis requiring hospitalization within the last three years
• Non-English speaking, illiterate, unable to comprehend consent
• Lack of contact information
• Uncontrolled narrow-angle glaucoma
• Currently being treatment with thioridazine (Mellaril)
• Patients taking opioids will be excluded if they are taking a dosage that exceeds an equivalent of 30 mg of morphine per day
• Patients taking more than one regular (not rescue) medication for pain
• Patients taking donepezil for dementia
• Patients with a baseline pain score less than 2 (0-10 scale) or greater than 8 (0-10) will be excluded

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01743976
• Other Study ID Numbers: IRB00022107; R01NS057594 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Wake Forest University Health Sciences ( Wake Forest University )
• Original Responsible Party: James C. Eisenach, M.D., Wake Forest University, Professor
• Current Study Sponsor: Wake Forest University
• Original Study Sponsor: Same as current
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

• Principal Investigator: James C Eisenach, M.D.; Wake Forest University Health Sciences

• PRS Account: Wake Forest University Health Sciences
• Verification Date: October 2020