Official Title: “Three Way Interaction Between Gabapentin, Duloxetine, and Donepezil in Patients With Diabetic Neuropathy”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Parallel Assignment

Study Primary Completion Date: April 2010

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, 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.

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.

Intervention(s) in this Clinical Trial

• Drug: donepezil
  • Group 1: Will receive donepezil 5mg once a day
• Drug: duloxetine
  • Group 2: Will receive duloxetine 30 mg twice a day
• Drug: donepezil 2.5 mg and duloxetine 30mg
  • Group 3: Will receive a combination of donepezil 2.5 mg and duloxetine 30mg
• Drug: placebo
  • Group 4: Will receive placebo pills

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Donepezil 5 mg once per day for 12 weeks. Gabapentin will be added to all groups at week 9.
• Active Comparator: 2
  • Group 2: Will receive duloxetine 30 mg twice a day for 12 weeks. Gabapentin will be added to all groups at week 9.
• Active Comparator: 3
  • Group 3: Will receive a combination of donepezil 2.5 mg and duloxetine 30mg for 12 weeks. Gabapentin will be added to all groups at week 9.
• Placebo Comparator: 4
  • Group 4:Will receive placebo pills. Gabapentin will be added to all groups at week 9.

Primary Measures

• Pain intensity measurements will be recorded twice daily, using McGill short form pain questionnaire on the PDA. The Visual Analog Pain Scale (VAS) will serve as the primary outcome measure.
  • Time Frame: Study completion
    Safety Issue?: No

Inclusion Criteria:

• Diagnosis of diabetic neuropathy
• Age 18-80
• Willing to temporarily discontinue gabapentin or monoamine reuptake inhibitors upon entry into the study

Exclusion Criteria:

• 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 80 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Wake Forest University

Overall Clinical Trial Officials and Contacts

James C Eisenach, MD Principal Investigator Wake Forest University  

Overall Contact: Regina Curry, RN, CCRC 336-716-4294 recurry@wfubmc.edu

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00619983

Study ID Number: IRB00003943

ClinicalTrials.gov Identifier: NCT00619983

Health Authority: United States: Institutional Review Board