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

Chronic Low Back Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00619983
• Other study ID #: IRB00003943
• Secondary ID: 5R01NS057594
• Status: Terminated
• Phase: Phase 4
• Start date: February 2008
• Est. completion date: May 2013

Study information

• Verified date: August 2018
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 22
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Back Pain
• Chronic Low Back Pain
• Diabetic Neuropathic Pain
• Diabetic Neuropathies
• Low Back Pain
• Neuralgia

Intervention

Drug:
• donepezil
Group 1: Will receive donepezil 5mg once a day
• duloxetine
Group 2: Will receive duloxetine 30 mg twice a day
• donepezil 2.5 mg and duloxetine 30mg
Group 3: Will receive a combination of donepezil 2.5 mg and duloxetine 30mg
• placebo
Group 4: Will receive placebo pills
• gabapentin
Week 8: all subjects will have open label gabapentin added to their randomized study medication

Locations

Country	Name	City	State
United States	Cleveland Clinic	Cleveland	Ohio
United States	Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Wake Forest University	National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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).	Study completion (16 weeks)