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| ID | Type | Description | Link |
|---|---|---|---|
| 5R01NS057594 | U.S. NIH Grant/Contract | View source |
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Study terminated due to low enrollment
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| Name | Class |
|---|---|
| National Institute of Neurological Disorders and Stroke (NINDS) | NIH |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Donepezil | Active Comparator | Donepezil 5 mg once per day for 12 weeks. Gabapentin will be titrated in all groups beginning at week 8. |
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| 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. |
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| 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. |
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| Placebo | Placebo Comparator | Group 4:Will receive placebo pills. Gabapentin will be titrated in all groups beginning at week 8. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| donepezil | Drug | Group 1: Will receive donepezil 5mg once a day |
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| Measure | Description | Time Frame |
|---|---|---|
| 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). | Study completion (16 weeks) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| James C Eisenach, MD | Wake Forest University Health Sciences | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Wake Forest University Baptist Medical Center | Winston-Salem | North Carolina | 27157 | United States | ||
Raw IPD will not be shared
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| ID | Title | Description |
|---|---|---|
| FG000 | Donepezil | Donepezil 5 mg /day from 2-14 weeks with gabapentin titrated beginning at week 8 and maintained until week 15. |
| FG001 | Duloxetine | Duloxetine 30 mg twice per day from 2-14 weeks with gabapentin titrated beginning at week 8 and maintained until week 15. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Test Drug Alone |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 19, 2010 |
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| duloxetine | Drug | Group 2: Will receive duloxetine 30 mg twice a day |
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| donepezil 2.5 mg and duloxetine 30mg | Drug | Group 3: Will receive a combination of donepezil 2.5 mg and duloxetine 30mg |
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| placebo | Drug | Group 4: Will receive placebo pills |
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| gabapentin | Drug | Week 8: all subjects will have open label gabapentin added to their randomized study medication |
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| Cleveland Clinic |
| Cleveland |
| Ohio |
| 44195 |
| United States |
| FG002 | Donepezil + Duloxetine | Donepezil 2.5 mg /day and duloxetine 30 mg / day from 2-14 weeks with gabapentin titrated beginning at week 8 and maintained until week 15. |
| FG003 | Placebo | Placebo from 2-14 weeks with gabapentin titrated beginning at week 8 and maintained until week 15. |
| COMPLETED |
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| NOT COMPLETED |
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| Test Drug Plus Gabapentin |
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| Gabapentin Alone |
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| ID | Title | Description |
|---|---|---|
| BG000 | Donepezil | Donepezil 5 mg /day from 2-14 weeks with gabapentin titrated beginning at week 8 and maintained until week 15. |
| BG001 | Duloxetine | Duloxetine 30 mg twice per day from 2-14 weeks with gabapentin titrated beginning at week 8 and maintained until week 15. |
| BG002 | Donepezil + Duloxetine | Donepezil 2.5 mg /day and duloxetine 30 mg / day from 2-14 weeks with gabapentin titrated beginning at week 8 and maintained until week 15. |
| BG003 | Placebo | Placebo from 2-14 weeks with gabapentin titrated beginning at week 8 and maintained until week 15. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | As noted in patient flow, data are available for only 14 of 22 subjects due to failure of the electronic daily diaries used to assess pain during the study and to study discontinuation in some cases | Posted | Median | Full Range | units on a scale | Study completion (16 weeks) |
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During the 16 week study
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Donepezil | Donepezil 5 mg /day from 2-14 weeks with gabapentin titrated beginning at week 8 and maintained until week 15. | 0 | 5 | 0 | 5 | 1 | 5 |
| EG001 | Duloxetine | Duloxetine 30 mg twice per day from 2-14 weeks with gabapentin titrated beginning at week 8 and maintained until week 15. | 0 | 5 | 0 | 5 | 0 | 5 |
| EG002 | Donepezil + Duloxetine | Donepezil 2.5 mg /day and duloxetine 30 mg / day from 2-14 weeks with gabapentin titrated beginning at week 8 and maintained until week 15. | 0 | 6 | 0 | 6 | 0 | 6 |
| EG003 | Placebo | Placebo from 2-14 weeks with gabapentin titrated beginning at week 8 and maintained until week 15. | 0 | 6 | 1 | 6 | 1 | 6 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Angina | Cardiac disorders | Non-systematic Assessment | Subject experienced chest pain and was hospitalized. Serial ECGs and troponins were negative for myocardial injury |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| nausea | Gastrointestinal disorders | Systematic Assessment | subject experienced nausea |
| |
| osteomyelitis | Infections and infestations | Systematic Assessment | subject experienced osteomyelitis of of second phalange |
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We recruited only a small proportion of the planned enrollment in the period of grant funding, leading to early termination of the study. Also, the failure of the electronic diaries and loss of primary outcome data prevented the planned analysis.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. James Eisenach | Wake Forest School of Medicine | 336-716-4182 | jimeisenach@gmail.com |
| Aug 10, 2017 |
| Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Apr 16, 2010 | Aug 10, 2017 | ICF_001.pdf |
| ID | Term |
|---|---|
| D003929 | Diabetic Neuropathies |
| D017116 | Low Back Pain |
| D000092122 | Bronchiolitis Obliterans Syndrome |
| ID | Term |
|---|---|
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D048909 | Diabetes Complications |
| D003920 | Diabetes Mellitus |
| D004700 | Endocrine System Diseases |
| D001416 | Back Pain |
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000092124 | Organizing Pneumonia |
| D001989 | Bronchiolitis Obliterans |
| D001988 | Bronchiolitis |
| D001991 | Bronchitis |
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D006086 | Graft vs Host Disease |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D000077265 | Donepezil |
| D000068736 | Duloxetine Hydrochloride |
| D000077206 | Gabapentin |
| ID | Term |
|---|---|
| D007189 | Indans |
| D007192 | Indenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D000588 | Amines |
| D005680 | gamma-Aminobutyric Acid |
| D000613 | Aminobutyrates |
| D002087 | Butyrates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D003509 | Cyclohexanecarboxylic Acids |
| D000146 | Acids, Carbocyclic |
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
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| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Test drug alone (6 weeks) |
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| Drug plus gabapentin (6 weeks) |
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| Gabapentin alone (2 weeks) |
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