Clinical trial NCT01743976: Donepezil Compared to Placebo in Patients With Chronic Neuropathic Pain
Official title: Donepezil Compared to Placebo in Patients With Chronic Neuropathic Pain
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Neuropathic Pain
Keywords: neuropathic pain
diabetic neuropathy
neuropathic pain after back surgery
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2012-12-06
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: McGill Short Form Pain Questionnaire (SF MPQ) Visual Analog Scale (VAS) Pain Intensity
timeFrame: baseline
measure: McGill Short Form Pain Questionnaire (SF MPQ) Visual Analog Scale (VAS) Pain Intensity
timeFrame: Week 8: last week of study drug treatment
measure: McGill Short Form Pain Questionnaire (SF MPQ) Visual Analog Scale (VAS) Pain Intensity
timeFrame: Week 10: last week of washout
Secondary outcomes:
measure: Average From Baseline Profile of Mood States-Short Form (POMS-SF) at 10 Weeks
timeFrame: baseline, week 8 after baseline, and week 10 after baseline
measure: Number of Days With Rescue Treatment
timeFrame: Days: baseline, week 8 after baseline, and week 10 after baseline
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: James C Eisenach, M.D.
role: PRINCIPAL_INVESTIGATOR
References: