Diabetic Neuropathic PainPhase 4NCT00619983
Three Way Interaction Between Gabapentin, Duloxetine, and Donepezil in Patients With Diabetic Neuropathy
A Phase 4 study testing donepezil, duloxetine and donepezil 2.5 mg and duloxetine 30mg in people with Diabetic Neuropathic Pain and Chronic Low Back Pain, run by Wake Forest University at 2 sites in United States.
Trial summary
The purpose of the study is to determine whether the combination of the the three drugs gabapentin, duloxetine, and donepezil are effective in treating pain in people with diabetic neuropathy or patients with failed low back syndrome (chronic back pain). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Diabetic Neuropathic Pain, Chronic Low Back Pain
- What is being tested?
- donepezil, duloxetine and donepezil 2.5 mg and duloxetine 30mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 2 sitesUnited States
- Study dates
- Feb 2008to May 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
- Age 18-80
- Willing to temporarily discontinue gabapentin or monoamine reuptake inhibitors upon entry into the study
Who cannot join
- Pregnancy
- Allergy to study medications
- Uncontrolled narrow-angle glaucoma
- Currently being treatment with thioridazine (Mellaril)
- Unstable medical conditions including cardiac, pulmonary, renal or hepatic diseases
- Treatment with a monoamine oxidase inhibitor (MAOI) within 14 days of randomization
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Cleveland Clinic
Cleveland, Ohio, 44195
Wake Forest University Baptist Medical Center
Winston-Salem, North Carolina, 27157
About this study
The purpose of the study is to determine whether the combination of the the three drugs gabapentin, duloxetine, and donepezil are effective in treating pain in people with diabetic neuropathy or patients with failed low back syndrome (chronic back pain).
Read the detailed description
Neuropathic pain is a complex and likely heterogeneous disorder, and we recognize that clinically useful agents such as opioids, gabapentin, and antidepressants may be effective precisely because they have multiple mechanisms of action at multiple sites. This study, however, will not only provide important mechanistic information regarding one cascade which can be manipulated for analgesia, but will also provide much needed systematic and practical guidance for multi-drug therapy in patients with neuropathic pain.
This study in patients with diabetic neuropathic pain and patients with failed low back syndrome, culminate in a quantitative description of interactions between activators of descending noradrenergic activity, norepinephrine transporter inhibitors, and cholinesterase inhibitors to exploit the plasticity of analgesia in chronic pain states. We will focus on practical applications, using clinically approved drugs, including gabapentin (Neurontin®) to activate noradrenergic activity, duloxetine (Cymbalta®) to inhibit the norepinephrine transporter, and donepezil (Aricept®), approved for the treatment of Alzheimer's dementia, but not previously tested to treat neuropathic pain, to inhibit cholinesterase.
After the baseline measurements and physical examination patients will be trained to use a Personal Digital Assistant (PDA) to answer questions about their diabetic neuropathic pain or their chronic back pain. Upon successful completion of these tasks the patients will be randomized to receive one of the drug choices or placebo (inactive pill).
The study will last for a total of 16 weeks and includes 5 visits to the research center with each visit lasting approximately 2 hours.
- Conditions
- Diabetic Neuropathic Pain, Chronic Low Back Pain
- Being tested
- donepezil, duloxetine, donepezil 2.5 mg and duloxetine 30mg, placebo, gabapentin
- Keywords
- Asymmetric Diabetic Proximal Motor Neuropathy, Diabetic Autonomic Neuropathy, Diabetic Neuralgia, Diabetic Neuropathy, Painful, Neuralgia, Diabetic, Low back pain, chronic
- Medical subject headings
- Diabetic Neuropathies, Low Back Pain, Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
donepezilDrug
Also called Aricept®
Group 1: Will receive donepezil 5mg once a day
duloxetineDrug
Also called Cymbalta®
Group 2: Will receive duloxetine 30 mg twice a day
donepezil 2.5 mg and duloxetine 30mgDrug
Also called Cymbalta®, Aricept®
Group 3: Will receive a combination of donepezil 2.5 mg and duloxetine 30mg
placeboDrug
Group 4: Will receive placebo pills
gabapentinDrug
Also called neurontin
Week 8: all subjects will have open label gabapentin added to their randomized study medication
| Study group | Role | What they receive |
|---|---|---|
| Donepezil | Active comparator | Donepezil 5 mg once per day for 12 weeks. Gabapentin will be titrated in all groups beginning at week 8. Receives: Drug: donepezil; Drug: gabapentin |
| Duloxetine | Active comparator | Group 2: Will receive duloxetine 30 mg twice a day for 12 weeks. Gabapentin will be titrated in all groups beginning at week 8. Receives: Drug: duloxetine; Drug: gabapentin |
| Donepezil + Duloxetine | Active comparator | Group 3: Will receive a combination of donepezil 2.5 mg and duloxetine 30mg for 12 weeks. Gabapentin will be titrated in all groups beginning at week 8. Receives: Drug: donepezil 2.5 mg and duloxetine 30mg; Drug: gabapentin |
| Placebo | Placebo comparator | Group 4:Will receive placebo pills. Gabapentin will be titrated in all groups beginning at week 8. Receives: Drug: placebo; Drug: gabapentin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Visual Analog Scale for Pain
The primary outcome measure is the visual analog scale (VAS) for pain, a 10 cm line upon which the subject marks their intensity of pain. The line is anchored on the left as "No pain at all" and on the right as "The worst pain imaginable". The score is the number of millimeters from the left origin of the line. The primary outcome measure for each period was the average value of all assessments for that period (2 weeks of measures for baseline, 6 weeks of measures for test drug alone, 6 weeks of measures for test drug plus gabapentin, and 2 weeks of measures for gabapentin alone).
Measured: Study completion (16 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2008 (estimated)
- Study startFeb 2008
- Primary completionMay 2013
- Study completionMay 2013
Why it stopped: Study terminated due to low enrollment
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 Diabetic 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
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- James C Eisenach, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00619983
- Sponsor's protocol ID
- IRB00003943
- Other IDs
- 5R01NS057594
- Status last verified
- Aug 2018
- First submitted
- 8 Feb 2008
- Last updated
- 11 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Raw IPD will not be shared
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Three Way Interaction Between Gabapentin, Duloxetine, and Donepezil in Patients With Diabetic Neuropathy
- ClinicalTrials.gov ID
- NCT00619983
- Acronym / sponsor ID
- IRB00003943
- Conditions
- Diabetic Neuropathic Pain, Chronic Low Back Pain
- Keywords
- Asymmetric Diabetic Proximal Motor Neuropathy, Diabetic Autonomic Neuropathy, Diabetic Neuralgia, Diabetic Neuropathy, Painful, Neuralgia, Diabetic, Low back pain, chronic
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study terminated due to low enrollment
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Wake Forest UniversityUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Feb 2008
- Primary completion
- May 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 21 Feb 2008 (estimated)
- Results
- Posted 10 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to determine whether the combination of the the three drugs gabapentin, duloxetine, and donepezil are effective in treating pain in people with diabetic neuropathy or patients with failed low back syndrome (chronic back pain).
Detailed description
Neuropathic pain is a complex and likely heterogeneous disorder, and we recognize that clinically useful agents such as opioids, gabapentin, and antidepressants may be effective precisely because they have multiple mechanisms of action at multiple sites. This study, however, will not only provide important mechanistic information regarding one cascade which can be manipulated for analgesia, but will also provide much needed systematic and practical guidance for multi-drug therapy in patients with neuropathic pain.
This study in patients with diabetic neuropathic pain and patients with failed low back syndrome, culminate in a quantitative description of interactions between activators of descending noradrenergic activity, norepinephrine transporter inhibitors, and cholinesterase inhibitors to exploit the plasticity of analgesia in chronic pain states. We will focus on practical applications, using clinically approved drugs, including gabapentin (Neurontin®) to activate noradrenergic activity, duloxetine (Cymbalta®) to inhibit the norepinephrine transporter, and donepezil (Aricept®), approved for the treatment of Alzheimer's dementia, but not previously tested to treat neuropathic pain, to inhibit cholinesterase.
After the baseline measurements and physical examination patients will be trained to use a Personal Digital Assistant (PDA) to answer questions about their diabetic neuropathic pain or their chronic back pain. Upon successful completion of these tasks the patients will be randomized to receive one of the drug choices or placebo (inactive pill).
The study will last for a total of 16 weeks and includes 5 visits to the research center with each visit lasting approximately 2 hours.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Donepezil | Active comparator | Drug: donepezil, Drug: gabapentinDonepezil 5 mg once per day for 12 weeks. Gabapentin will be titrated in all groups beginning at week 8. |
| Duloxetine | Active comparator | Drug: duloxetine, Drug: gabapentinGroup 2: Will receive duloxetine 30 mg twice a day for 12 weeks. Gabapentin will be titrated in all groups beginning at week 8. |
| Donepezil + Duloxetine | Active comparator | Drug: donepezil 2.5 mg and duloxetine 30mg, Drug: gabapentinGroup 3: Will receive a combination of donepezil 2.5 mg and duloxetine 30mg for 12 weeks. Gabapentin will be titrated in all groups beginning at week 8. |
| Placebo | Placebo comparator | Drug: placebo, Drug: gabapentinGroup 4:Will receive placebo pills. Gabapentin will be titrated in all groups beginning at week 8. |
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
- Age 18-80
- Willing to temporarily discontinue gabapentin or monoamine reuptake inhibitors upon entry into the study
Key exclusion criteria (6 listed)
- Pregnancy
- Allergy to study medications
- Uncontrolled narrow-angle glaucoma
- Currently being treatment with thioridazine (Mellaril)
- Unstable medical conditions including cardiac, pulmonary, renal or hepatic diseases
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: Aricept®Group 1: Will receive donepezil 5mg once a day | Drug | Donepezil |
| duloxetineAlso: Cymbalta®Group 2: Will receive duloxetine 30 mg twice a day | Drug | Duloxetine |
| donepezil 2.5 mg and duloxetine 30mgAlso: Cymbalta®, Aricept®Group 3: Will receive a combination of donepezil 2.5 mg and duloxetine 30mg | Drug | Donepezil + Duloxetine |
| placeboGroup 4: Will receive placebo pills | Drug | Placebo |
| gabapentinAlso: neurontinWeek 8: all subjects will have open label gabapentin added to their randomized study medication | Drug | Donepezil, Donepezil + Duloxetine, Duloxetine, Placebo |
Primary outcome
Visual Analog Scale for Pain
Time frame: Study completion (16 weeks)
The primary outcome measure is the visual analog scale (VAS) for pain, a 10 cm line upon which the subject marks their intensity of pain. The line is anchored on the left as "No pain at all" and on the right as "The worst pain imaginable". The score is the number of millimeters from the left origin of the line. The primary outcome measure for each period was the average value of all assessments for that period (2 weeks of measures for baseline, 6 weeks of measures for test drug alone, 6 weeks of measures for test drug plus gabapentin, and 2 weeks of measures for gabapentin alone).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. Raw IPD will not be shared
Related trials for Diabetic Neuropathic Pain
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A Chronic Pain Master Protocol (CPMP): A Study of LY4065967 in Participants With Diabetic Peripheral Neuropathic Pain
Diabetic Peripheral Neuropathic Pain
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Comparative Effects of tDCS and tACS on Pain, Dexterity, and Strength in Diabetic Peripheral Neuropathy
Diabetic Peripheral Neuropathy (DPN)
Active, not recruitingPhase 3
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Diabetic Peripheral Neuropathic Pain
Not yet recruitingPhase 2
Perineural Botulinum Toxin Injection Versus Oral Duloxetine in Relief of Foot Pain in Painful Peripheral Diabetic Neuropathy
Diabetic Peripheral Neuropathy, Painful Diabetic Neuropathy
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, MD 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, duloxetine and donepezil 2.5 mg and duloxetine 30mg in people with Diabetic Neuropathic Pain and Chronic Low Back 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 6 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 11 Sep 2018. 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 10 Aug 2017). 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?
Visual Analog Scale for Pain (time frame: Study completion (16 weeks)). 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 11 Sep 2018.