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 )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Neuropathic Pain	Drug: Donepezil; Drug: Placebo	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Donepezil Compared to Placebo in Patients With Chronic Neuropathic Pain
• Actual Study Start Date: December 2012
• Actual Primary Completion Date: October 23, 2013
• Actual Study Completion Date: October 23, 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Donepezil; donepezil 5 mg every day	Drug: Donepezil; donepezil 5 mg once daily for 6 weeks; Other Name: Aricept
Placebo Comparator: Placebo; Placebo (sugar pill) every day	Drug: Placebo; placebo or sugar pill will be taken once daily for 6 weeks; Other Name: sugar pill

Outcome Measures

Primary Outcome Measures :

1. 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.
2. 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.
3. 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.

Secondary Outcome Measures :

1. 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.
2. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, North Carolina

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States, 27157

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States, 27295

Sponsors and Collaborators

Wake Forest University

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

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

  Study Documents (Full-Text)

Documents provided by Wake Forest University Health Sciences ( Wake Forest University ):

Study Protocol and Statistical Analysis Plan  [PDF] November 19, 2012

Informed Consent Form  [PDF] September 14, 2015

More Information

• Responsible Party: Wake Forest University
• ClinicalTrials.gov Identifier: NCT01743976
• Other Study ID Numbers: IRB00022107; R01NS057594 ( U.S. NIH Grant/Contract )
• First Posted: December 6, 2012
• Results First Posted: November 18, 2020
• Last Update Posted: March 2, 2021
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Wake Forest University Health Sciences ( Wake Forest University ):

neuropathic pain; diabetic neuropathy; neuropathic pain after back surgery

Additional relevant MeSH terms:

Neuralgia; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Donepezil; Cholinesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Nootropic Agents