This trial is active, not recruiting.

Condition neuropathic pain
Treatments donepezil, placebo
Phase phase 4
Sponsor Wake Forest University
Collaborator National Institute of Neurological Disorders and Stroke (NINDS)
Start date December 2012
End date December 2016
Trial size 33 participants
Trial identifier NCT01743976, 00022107, R01NS057594


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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator, outcomes assessor)
Primary purpose treatment
donepezil 5 mg every day
donepezil Aricept
donepezil 5 mg once daily for 6 weeks
(Placebo Comparator)
Placebo (sugar pill) every day
placebo sugar pill
placebo or sugar pill will be taken once daily for 6 weeks

Primary Outcomes

Pain Intensity
time frame: 10 weeks

Eligibility Criteria

Male or female participants from 18 years up to 80 years old.

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

Additional Information

Official title Donepezil Compared to Placebo in Patients With Chronic Neuropathic Pain
Principal investigator James C Eisenach, M.D.
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.
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Wake Forest School of Medicine.