Three Way Interaction Between Gabapentin, Duloxetine, and Donepezil in Patients With Diabetic Neuropathy

Condition(s) targeted: Diabetic Neuropathic Pain; Chronic Low Back Pain

Intervention: donepezil (Drug); duloxetine (Drug); donepezil 2.5 mg and duloxetine 30mg (Drug); placebo (Drug); gabapentin (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: Wake Forest University

Official(s) and/or principal investigator(s):
James C Eisenach, MD, Principal Investigator, Affiliation: Wake Forest University

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

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).

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

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

Primary outcome: 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.

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.

Minimum age: 18 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

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

Regina Curry, RN, CCRC, Phone: 336-716-4294, Email: recurry@wfubmc.edu

Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina 27157, United States; Recruiting
Regina Curry, RN, CCRC, Phone: 336-716-4294, Email: recurry@wfubmc.edu
James C. Eisenach, MD, Principal Investigator
James C. Crews, MD, Sub-Investigator
James B. Caress, MD, Sub-Investigator

Starting date: February 2008
Ending date: July 2010
Last updated: August 14, 2009