Neuropathic PainPhase 4NCT01743976
Donepezil Compared to Placebo in Patients With Chronic Neuropathic Pain
A Phase 4 study testing Donepezil in people with Neuropathic Pain, run by Wake Forest University at 2 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Neuropathic Pain
- What is being tested?
- Donepezil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 2 sitesUnited States
- Study dates
- Dec 2012to 23 Oct 2013
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of diabetic neuropathy or failed back syndrome with neuropathic symptoms
- Age 18-80
- Taking a stable dose of gabapentin or pregabalin
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, 27157
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27295
About this study
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.
Read the 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
- Being tested
- Donepezil, Placebo
- Keywords
- neuropathic pain, diabetic neuropathy, neuropathic pain after back surgery
- Medical subject headings
- Neuralgia, Diabetic Neuropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DonepezilDrug
Also called Aricept
donepezil 5 mg once daily for 6 weeks
PlaceboDrug
Also called sugar pill
placebo or sugar pill will be taken once daily for 6 weeks
| Study group | Role | What they receive |
|---|---|---|
| Donepezil | Experimental | donepezil 5 mg every day Receives: Drug: Donepezil |
| Placebo | Placebo comparator | Placebo (sugar pill) every day Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: baseline
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.
Measured: Week 8: last week of study drug treatment
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.
Measured: Week 10: last week of washout
Secondary outcomes (2)
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.
Measured: baseline, week 8 after baseline, and week 10 after baseline
Number of Days With Rescue Treatment
Questionnaires detailing the amount of rescue pain medications will be completed twice daily.
Measured: Days: baseline, week 8 after baseline, and week 10 after baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2012 (estimated)
- Study startDec 2012
- Primary completion23 Oct 2013
- Study completion23 Oct 2013
Why it stopped: Failure to recruit subjects
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Neuropathic PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- James C Eisenach, M.D., Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01743976
- Sponsor's protocol ID
- IRB00022107
- Other IDs
- R01NS057594
- Status last verified
- Oct 2020
- First submitted
- 20 Nov 2012
- Last updated
- 2 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Donepezil Compared to Placebo in Patients With Chronic Neuropathic Pain
- ClinicalTrials.gov ID
- NCT01743976
- Acronym / sponsor ID
- IRB00022107
- Conditions
- Neuropathic Pain
- Keywords
- neuropathic pain, diabetic neuropathy, neuropathic pain after back surgery
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Failure to recruit subjects
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Wake Forest UniversityUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Dec 2012 (actual)
- Primary completion
- 23 Oct 2013 (actual)
- Study completion
- 23 Oct 2013 (actual)
- First posted
- 6 Dec 2012 (estimated)
- Results
- Posted 18 Nov 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Donepezil | Experimental | Drug: Donepezildonepezil 5 mg every day |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo (sugar pill) every day |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosis of diabetic neuropathy or failed back syndrome with neuropathic symptoms
- Age 18-80
- Taking a stable dose of gabapentin or pregabalin
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DonepezilAlso: Ariceptdonepezil 5 mg once daily for 6 weeks | Drug | Donepezil |
| PlaceboAlso: sugar pillplacebo or sugar pill will be taken once daily for 6 weeks | Drug | Placebo |
Primary outcome
McGill Short Form Pain Questionnaire (SF MPQ) Visual Analog Scale (VAS) Pain Intensity
Time frame: baseline
A greater number is considered a worse outcome. VAS Range (0-10) 0=No Pain 10=The worst pain imaginable.
McGill Short Form Pain Questionnaire (SF MPQ) Visual Analog Scale (VAS) Pain Intensity
Time frame: 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.
McGill Short Form Pain Questionnaire (SF MPQ) Visual Analog Scale (VAS) Pain Intensity
Time frame: 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.
2 secondary outcomes
Average From Baseline Profile of Mood States-Short Form (POMS-SF) at 10 Weeks
Time frame: baseline, week 8 after baseline, and week 10 after baseline
Number of Days With Rescue Treatment
Time frame: Days: baseline, week 8 after baseline, and week 10 after baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James C Eisenach, M.D. principal investigator
Wake Forest University Health Sciences
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Donepezil in people with Neuropathic Pain, run by Wake Forest University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
McGill Short Form Pain Questionnaire (SF MPQ) Visual Analog Scale (VAS) Pain Intensity (time frame: baseline). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2021.