Donepezil Compared to Placebo in Patients With Chronic Neuropathic Pain

Phase 4

Terminated

• Conditions: Neuropathic Pain
• Interventions: Drug: Placebo; Drug: Donepezil

• Registration Number: NCT01743976
• Lead Sponsor: Wake Forest University

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 Timeline

• Study First Submitted: 2012-11-20
• Study Start: 2012-12
• Study First Submitted QC: 2012-12-04
• Study First Posted: 2012-12-06
• Primary Completion: 2013-10-23
• Study Completion: 2013-10-23
• Results First Submitted: 2020-09-22
• Status Verified: 2020-10
• Results First Submitted QC: 2020-11-10
• Results First Posted: 2020-11-18
• Last Update Submitted: 2021-02-05
• Last Update Posted: 2021-03-02

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 5

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo (sugar pill) every day
Donepezil	Donepezil	donepezil 5 mg every day

Primary Outcome Measures

Name	Time	Method
McGill Short Form Pain Questionnaire (SF MPQ) Visual Analog Scale (VAS) Pain Intensity	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

Name	Time	Method
Number of Days With Rescue Treatment	Days: baseline, week 8 after baseline, and week 10 after baseline	Questionnaires detailing the amount of rescue pain medications will be completed twice daily.
Average From Baseline Profile of Mood States-Short Form (POMS-SF) at 10 Weeks	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.

Trial Locations

Locations (2)

Wake Forest Baptist Health; 🇺🇸 Winston-Salem, North Carolina, United States

Wake Forest Baptist Medical Center; 🇺🇸 Winston-Salem, North Carolina, United States