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

Wake Forest University (WFU)

Status and phase: Terminated; Phase 4

Conditions: Chronic Low Back Pain; Diabetic Neuropathic Pain

Treatments: Drug: placebo; Drug: donepezil 2.5 mg and duloxetine 30mg; Drug: donepezil; Drug: duloxetine; Drug: gabapentin

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00619983

IRB00003943

5R01NS057594 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 22 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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22 participants in 4 patient groups, including a placebo group

Donepezil

Active Comparator group

Description:

Donepezil 5 mg once per day for 12 weeks. Gabapentin will be titrated in all groups beginning at week 8.

Treatment:

Drug: gabapentin

Drug: donepezil

Duloxetine

Active Comparator group

Description:

Group 2: Will receive duloxetine 30 mg twice a day for 12 weeks. Gabapentin will be titrated in all groups beginning at week 8.

Treatment:

Drug: gabapentin

Drug: duloxetine

Donepezil + Duloxetine

Active Comparator group

Description:

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.

Treatment:

Drug: gabapentin

Drug: donepezil 2.5 mg and duloxetine 30mg

Placebo

Placebo Comparator group

Description:

Group 4:Will receive placebo pills. Gabapentin will be titrated in all groups beginning at week 8.

Treatment:

Drug: gabapentin

Drug: placebo