Donepezil Compared to Placebo in Patients With Chronic Neuropathic Pain

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.

Study Overview

• Status: Terminated
• Conditions: Neuropathic Pain
• Intervention / Treatment: Drug: Donepezil; Drug: Placebo

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
• Enrollment (Actual): 5
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center
    • Winston-Salem, North Carolina, United States, 27295
      • Wake Forest Baptist Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Donepezil; donepezil 5 mg every day	Drug: Donepezil; donepezil 5 mg once daily for 6 weeks; Other Names: Aricept
PLACEBO_COMPARATOR: Placebo; Placebo (sugar pill) every day	Drug: Placebo; placebo or sugar pill will be taken once daily for 6 weeks; Other Names: sugar pill

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Wake Forest University
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2012
• Primary Completion (ACTUAL): October 23, 2013
• Study Completion (ACTUAL): October 23, 2013

Study Registration Dates

• First Submitted: November 20, 2012
• First Submitted That Met QC Criteria: December 4, 2012
• First Posted (ESTIMATE): December 6, 2012

Study Record Updates

• Last Update Posted (ACTUAL): March 2, 2021
• Last Update Submitted That Met QC Criteria: February 5, 2021
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: neuropathic pain; diabetic neuropathy; neuropathic pain after back surgery
• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Nootropic Agents; Cholinesterase Inhibitors; Donepezil
• Other Study ID Numbers: IRB00022107; R01NS057594 (NIH)

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