Donepezil Compared to Placebo in Patients With Chronic Neuropathic Pain

Neuropathic Pain Clinical Trial

Official title:

Donepezil Compared to Placebo in Patients With Chronic Neuropathic Pain

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01743976
• Other study ID #: IRB00022107
• Secondary ID: R01NS057594
• Status: Terminated
• Phase: Phase 4
• Start date: December 2012
• Est. completion date: October 23, 2013

Study information

• Verified date: October 2020
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: October 23, 2013
• Est. primary completion date: October 23, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Neuralgia
• Neuropathic Pain

Intervention

Drug:
• Donepezil
donepezil 5 mg once daily for 6 weeks
• Placebo
placebo or sugar pill will be taken once daily for 6 weeks

Locations

Country	Name	City	State
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Wake Forest University	National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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