Clinical trial NCT01363284: Pretreatment Identification of Duloxetine Success in Neuropathic Pain Patients
Official title: Pretreatment Identification of Duloxetine Success in Neuropathic Pain Patients Based on Assessment of Endogenous Analgesia Capabilities
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes
Painful Neuropathy
Lead sponsor: Rambam Health Care Campus
Sponsor class: OTHER
Collaborators: name: Eli Lilly and Company
First posted: 2011-06-01
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to identify, prior to prescribing, which neuropathic pain patients will benefit from duloxetine more specific the investigators aims are to:

* Verify whether presence of chronic pain alters the pain modulation mechanisms, such as DNIC (diffuse noxious inhibitory control) and TS (temporal summation).
* Investigate whether anti-neuropathic medications such as duloxetine indeed change the pain modulation profile, and whether this profile change is associated with a reduction of clinical pain.

Detailed description: There is no accepted practice for selecting among recommended medications for the individual neuropathic pain patient. Guidelines published to date provided the evidence for their efficacy, however, data is not available on how to choose the right medication for the right patient in order to avoid long 'trial and error's. We hypothesize that medications affecting specific process of pain modulation will be more efficacious in patients expressing dysfunction of that specific process. Therefore, medications that enhance descending inhibition such as SSNRI will be more efficacious in patients with less-efficient pain inhibition. The latter is assessed by the conditioned pain modulation (CPM) paradigm. Accordingly, the aim of this study is to examine this hypothesis in painful diabetic neuropathy patients, using duloxetine, an SSNRI agent assumed to augment descending pain inhibition by reuptake inhibition of noradrenalin and serotonin in the spinal cord dorsal horn synapses. We expect to find better effect of duloxetine in those patients whose pain inhibition capability is less efficient, as expressed by their baseline CPM. Further, we aim to evaluate whether pro-nocieptive pattern of pain modulation indeed reverses in response to treatment. This will be explored by comparing the CPM responses before and after treatment, and by correlating pain alleviation with the possible changes in CPM.

Eligibility criteria: Inclusion Criteria:

* Patients diagnosed as having painful diabetic neuropathy.
* Pain is experienced for more than 3 months.
* Pain severity is ≥ 4 on a 0-10 scale (last month average).

Exclusion Criteria:

* Patient already receiving duloxetine or another SNRI/SSRI.
* Known hypersensitivity to duloxetine or any of the inactive ingredients.
* Treatment with a monoamine oxidase inhibitor (MAOI) within 14 days of randomization or potential need to use an MAOI during the study or within 5 days of discontinuation of study drug.
* Uncontrolled narrow-angle glaucoma
* Because of the risk of serious ventricular arrhythmias and sudden death potentially associated with elevated plasma levels of thioridazine (Mellaril), Cymbalta and thioridazine should not be co-administered
* Inability to perform psychophysical testing, due to language or perceptual barriers.

Primary outcomes:
measure: Prediction of duloxetine pain relief efficacy by pre-treatment extent of the CPM response
timeFrame: 2 year
Secondary outcomes:
measure: Treatment-related increase in CPM response
timeFrame: 2 years
Other outcomes:
Locations:
city: Haifa
country: Israel
facility: Rambam Medical center
Study officials:
affiliation: Rambam Health Care Campus
name: David Yarnitsky, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yarnitsky D, Granot M, Nahman-Averbuch H, Khamaisi M, Granovsky Y. Conditioned pain modulation predicts duloxetine efficacy in painful diabetic neuropathy. Pain. 2012 Jun;153(6):1193-1198. doi: 10.1016/j.pain.2012.02.021. Epub 2012 Apr 3.