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

This study has been terminated.
(Study terminated due to low enrollment)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
James C. Eisenach, M.D., Wake Forest University
ClinicalTrials.gov Identifier:
NCT00619983
First received: February 8, 2008
Last updated: May 15, 2013
Last verified: May 2013
  Purpose

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).


Condition Intervention
Diabetic Neuropathic Pain
Chronic Low Back Pain
Drug: donepezil
Drug: duloxetine
Drug: donepezil 2.5 mg and duloxetine 30mg
Drug: placebo
Drug: gabapentin

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Three Way Interaction Between Gabapentin, Duloxetine, and Donepezil in Patients With Diabetic Neuropathy

Resource links provided by NLM:


Further study details as provided by Wake Forest School of Medicine:

Primary Outcome 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 (16 weeks) ] [ Designated as safety issue: No ]

Enrollment: 22
Study Start Date: February 2008
Estimated Study Completion Date: May 2013
Estimated Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Donepezil 5 mg once per day for 12 weeks. Gabapentin will be added to all groups at week 9.
Drug: donepezil
Group 1: Will receive donepezil 5mg once a day
Other Name: Aricept®
Drug: gabapentin
Week 8: all subjects will have open label gabapentin added to their randomized study medication
Other Name: neurontin
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.
Drug: duloxetine
Group 2: Will receive duloxetine 30 mg twice a day
Other Name: Cymbalta®
Drug: gabapentin
Week 8: all subjects will have open label gabapentin added to their randomized study medication
Other Name: neurontin
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.
Drug: donepezil 2.5 mg and duloxetine 30mg
Group 3: Will receive a combination of donepezil 2.5 mg and duloxetine 30mg
Other Names:
  • Cymbalta®
  • Aricept®
Drug: gabapentin
Week 8: all subjects will have open label gabapentin added to their randomized study medication
Other Name: neurontin
Placebo Comparator: 4
Group 4:Will receive placebo pills. Gabapentin will be added to all groups at week 9.
Drug: placebo
Group 4: Will receive placebo pills
Drug: gabapentin
Week 8: all subjects will have open label gabapentin added to their randomized study medication
Other Name: neurontin

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00619983

Locations
United States, North Carolina
Wake Forest University Baptist Medical Center
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
Wake Forest School of Medicine
Investigators
Principal Investigator: James C Eisenach, MD Wake Forest School of Medicine
  More Information

No publications provided

Responsible Party: James C. Eisenach, M.D., Professor, Wake Forest University
ClinicalTrials.gov Identifier: NCT00619983     History of Changes
Other Study ID Numbers: IRB00003943, NS59574
Study First Received: February 8, 2008
Last Updated: May 15, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Wake Forest School of Medicine:
Asymmetric Diabetic Proximal Motor Neuropathy
Diabetic Autonomic Neuropathy
Diabetic Neuralgia
Diabetic Neuropathy, Painful
Neuralgia, Diabetic
Low back pain, chronic

Additional relevant MeSH terms:
Back Pain
Diabetic Neuropathies
Low Back Pain
Neuralgia
Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Peripheral Nervous System Diseases
Neuromuscular Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Gabapentin
Duloxetine
Donepezil
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anticonvulsants
Antiparkinson Agents
Anti-Dyskinesia Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on July 23, 2014