Donepezil Compared to Placebo in Patients With Chronic Neuropathic Pain

• Sponsor: Wake Forest University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01743976
• Collaborator: National Institute of Neurological Disorders and Stroke (NINDS) (NIH)
• Enrollment: 5
• Locations: 2
• Arms: 2
• Actual Duration (Months): 10.7
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Neuropathic Pain	Drug: Donepezil; Drug: Placebo	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Donepezil Compared to Placebo in Patients With Chronic Neuropathic Pain
• Actual Study Start Date: Dec 1, 2012
• Actual Primary Completion Date: Oct 23, 2013
• Actual Study Completion Date: Oct 23, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Donepezil donepezil 5 mg every day	Drug: Donepezil; donepezil 5 mg once daily for 6 weeks; Other Names: Aricept
Placebo Comparator: Placebo Placebo (sugar pill) every day	Drug: Placebo; placebo or sugar pill will be taken once daily for 6 weeks; Other Names: sugar pill

Outcome Measures

Primary Outcome Measures

1. McGill Short Form Pain Questionnaire (SF MPQ) Visual Analog Scale (VAS) Pain Intensity [baseline]

   A greater number is considered a worse outcome. VAS Range (0-10) 0=No Pain 10=The worst pain imaginable.

2. McGill Short Form Pain Questionnaire (SF MPQ) Visual Analog Scale (VAS) Pain Intensity [Week 8: last week of study drug treatment]

   A greater number is considered a worse outcome. VAS Range (0-10) 0=No Pain 10=The worst pain imaginable.

3. McGill Short Form Pain Questionnaire (SF MPQ) Visual Analog Scale (VAS) Pain Intensity [Week 10: last week of washout]

   A greater number is considered a worse outcome. VAS Range (0-10) 0=No Pain 10=The worst pain imaginable.

Secondary Outcome Measures

1. Average From Baseline Profile of Mood States-Short Form (POMS-SF) at 10 Weeks [baseline, week 8 after baseline, and week 10 after baseline]

   The questionnaire records total mood disturbance. The scale ranges from 0-100 with a greater number denoting a worse outcome.

2. Number of Days With Rescue Treatment [Days: baseline, week 8 after baseline, and week 10 after baseline]

   Questionnaires detailing the amount of rescue pain medications will be completed twice daily.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina	United States	27157
2	Wake Forest Baptist Health	Winston-Salem	North Carolina	United States	27295

Sponsors and Collaborators

• Wake Forest University
• National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

• Principal Investigator: James C Eisenach, M.D., Wake Forest University Health Sciences

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 19, 2012
• Informed Consent Form - Sep 14, 2015

More Information

Publications

None provided.

• Responsible Party: Wake Forest University
• ClinicalTrials.gov Identifier: NCT01743976
• Other Study ID Numbers: IRB00022107; R01NS057594
• First Posted: Dec 6, 2012
• Last Update Posted: Mar 2, 2021
• Last Verified: Oct 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Wake Forest University: neuropathic pain; diabetic neuropathy; neuropathic pain after back surgery
• Additional relevant MeSH terms: Neuralgia; Donepezil

Study Results

Participant Flow

Arm/Group Title	Donepezil	Placebo
Arm/Group Description	donepezil 5 mg every day Donepezil: donepezil 5 mg once daily for 6 weeks	Placebo (sugar pill) every day Placebo: placebo or sugar pill will be taken once daily for 6 weeks
Period Title: Overall Study
STARTED	2	3
COMPLETED	2	3
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Donepezil	Placebo	Total
Arm/Group Description	donepezil 5 mg every day Donepezil: donepezil 5 mg once daily for 6 weeks	Placebo (sugar pill) every day Placebo: placebo or sugar pill will be taken once daily for 6 weeks	Total of all reporting groups
Overall Participants	2	3	5
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	44	52	50
Sex: Female, Male (Count of Participants)
Female	2 100%	1 33.3%	3 60%
Male	0 0%	2 66.7%	2 40%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	2 100%	3 100%	5 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 100%	2 66.7%	4 80%
White	0 0%	1 33.3%	1 20%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	2 100%	3 100%	5 100%

Outcome Measures

1. Primary Outcome

Title	McGill Short Form Pain Questionnaire (SF MPQ) Visual Analog Scale (VAS) Pain Intensity
Description	A greater number is considered a worse outcome. VAS Range (0-10) 0=No Pain 10=The worst pain imaginable.
Time Frame	baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Donepezil	Placebo
Arm/Group Description	donepezil 5 mg every day Donepezil: donepezil 5 mg once daily for 6 weeks	Placebo (sugar pill) every day Placebo: placebo or sugar pill will be taken once daily for 6 weeks
Measure Participants	2	3
Median (Full Range) [units on the scale]	3.0	5.0

2. Secondary Outcome

Title	Average From Baseline Profile of Mood States-Short Form (POMS-SF) at 10 Weeks
Description	The questionnaire records total mood disturbance. The scale ranges from 0-100 with a greater number denoting a worse outcome.
Time Frame	baseline, week 8 after baseline, and week 10 after baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Donepezil	Placebo
Arm/Group Description	donepezil 5 mg every day Donepezil: donepezil 5 mg once daily for 6 weeks	Placebo (sugar pill) every day Placebo: placebo or sugar pill will be taken once daily for 6 weeks
Measure Participants	2	3
baseline	27	53
Week 8 after Baseline	25	24
Week 10 after Baseline	33	24

3. Secondary Outcome

Title	Number of Days With Rescue Treatment
Description	Questionnaires detailing the amount of rescue pain medications will be completed twice daily.
Time Frame	Days: baseline, week 8 after baseline, and week 10 after baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Donepezil	Placebo
Arm/Group Description	donepezil 5 mg every day Donepezil: donepezil 5 mg once daily for 6 weeks	Placebo (sugar pill) every day Placebo: placebo or sugar pill will be taken once daily for 6 weeks
Measure Participants	2	3
Baseline	.5	0
Week 8 after Baseline	0	0
Week 10 after Baseline	0	0

4. Primary Outcome

Title	McGill Short Form Pain Questionnaire (SF MPQ) Visual Analog Scale (VAS) Pain Intensity
Description	A greater number is considered a worse outcome. VAS Range (0-10) 0=No Pain 10=The worst pain imaginable.
Time Frame	Week 8: last week of study drug treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Donepezil	Placebo
Arm/Group Description	donepezil 5 mg every day Donepezil: donepezil 5 mg once daily for 6 weeks	Placebo (sugar pill) every day Placebo: placebo or sugar pill will be taken once daily for 6 weeks
Measure Participants	2	3
Median (Full Range) [units on the scale]	0.7	2.4

5. Primary Outcome

Title	McGill Short Form Pain Questionnaire (SF MPQ) Visual Analog Scale (VAS) Pain Intensity
Description	A greater number is considered a worse outcome. VAS Range (0-10) 0=No Pain 10=The worst pain imaginable.
Time Frame	Week 10: last week of washout

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Donepezil	Placebo
Arm/Group Description	donepezil 5 mg every day Donepezil: donepezil 5 mg once daily for 6 weeks	Placebo (sugar pill) every day Placebo: placebo or sugar pill will be taken once daily for 6 weeks
Measure Participants	2	3
Median (Full Range) [units on the scale]	0.4	2.8

Adverse Events

Arm/Group Title	Donepezil		Placebo
Arm/Group Description	donepezil 5 mg every day Donepezil: donepezil 5 mg once daily for 6 weeks		Placebo (sugar pill) every day Placebo: placebo or sugar pill will be taken once daily for 6 weeks
All Cause Mortality
	Donepezil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Donepezil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	Donepezil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/3 (0%)

Limitations/Caveats

Early termination leading to small numbers of subjects.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.