Donepezil Compared to Placebo in Patients With Chronic Neuropathic Pain

NCT ID: NCT01743976

Last Updated: 2021-03-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2013-10-23

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.

Conditions

Neuropathic Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Donepezil

donepezil 5 mg every day

Group Type: EXPERIMENTAL

Donepezil

Intervention Type: DRUG

donepezil 5 mg once daily for 6 weeks

Placebo

Placebo (sugar pill) every day

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

placebo or sugar pill will be taken once daily for 6 weeks

Interventions

Donepezil

donepezil 5 mg once daily for 6 weeks

Intervention Type: DRUG

Placebo

placebo or sugar pill will be taken once daily for 6 weeks

Intervention Type: DRUG

Other Intervention Names

Aricept; sugar pill

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Wake Forest University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

James C Eisenach, M.D.

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Locations

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

R01NS057594

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00022107

Identifier Type: -

Identifier Source: org_study_id