Donepezil Compared to Placebo in Patients With Chronic Neuropathic Pain

Study Overview
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Brief Summary
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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
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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.

Official Title
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Donepezil Compared to Placebo in Patients With Chronic Neuropathic Pain

Conditions
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Neuropathic Pain

Intervention / Treatment
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* Drug: Donepezil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Donepezil<br>donepezil 5 mg every day | Drug: Donepezil<br>* donepezil 5 mg once daily for 6 weeks<br>* Other names: Aricept;|
| Placebo Comparator: Placebo<br>Placebo (sugar pill) every day | Drug: Placebo<br>* placebo or sugar pill will be taken once daily for 6 weeks<br>* Other names: sugar pill;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neuropathic pain, diabetic neuropathy, neuropathic pain after back surgery