Functional Imaging of the Therapeutic Effect of Pregabalin in Treatment for Neuropathic Pain

Study Overview
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Brief Summary
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Functional Imaging of the therapeutic effect of Pregabalin in treatment for neuropathic pain in patients with Diabetic Polyneuropathy using proton Magnetic Resonance Spectroscopy (MRS): The aim of our study is to investigate the effect of Pregabalin as a treatment for neuropathic pain in a homogeneous study population, using proton MRS (1H MRS) focusing on four regions of interest (bilateral thalami, rostral anterior cingulated cortex (rACC) and dominant dorsolateral prefrontal cortex (DLPC).

Detailed Description
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spectrum measurements at: thalamus left thalamus right rostral anterior cingulated cortex dominant dorsolateral prefrontal cortex measurements: gamma-aminobutyric acid (GABA) glutamate (Glu) glutamine (Gln) N-acetylaspartate (NAA) Choline-containing compounds (Cho) Creatine plus phophocreatine (total creatine: Cr) Myo-inositiol (Ins) Choline (Cho) Glucose (Glc) Lactate (Lac)

Official Title
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Functional Imaging of the Therapeutic Effect of Pregabalin in Treatment for Neuropathic Pain in Patients With Diabetic Polyneuropathy Using Proton MR Spectroscopy

Conditions
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Diabetic Neuropathies, Pain

Intervention / Treatment
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* Other: MR Spectroscopy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Patients with painful DPN Patient willing to provide informed consent Type 1 or type 2 diabetes with HbA1c ≤ 11% Stable antidiabetic medication for 30 days prior to randomization Duration of painful DPN ≥ 3 months Visual analogue scale (VAS) score ≥ 4 Exclusion Criteria: Creatinine clearance ≤ 60mL/min Presence of other clinically significant or disabling chronic pain condition Active malignancy Evidence of an active disruptive psychiatric disorder or other known condition that might influence the perception of pain, compliance to intervention and/or ability to evaluate treatment outcome as determined by the investigator Life expectancy less than 1 year Existing or planned pregnancy Extreme fear for entering MRI General contraindication for MRI (pacemaker, etc…) Patients participating in other clinical trials Age <18 years Prior use of potential retinotoxins Prohibited medications without proper wash-out period (>7days, depending on the type of medication): medications and supplements commonly used for relief of neuropathic pain antiepileptics antidepressants (except for stable regiments of SSRIs for treatment of anxiety or depression) NSAID

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pregabalin<br> | Other: MR Spectroscopy<br>* During each MR Spectroscopy session, we will measure at regions of interest (rACC, both thalami, dominant DLPC) the levels of the following biochemical substances: gamma-aminobutyric acid (GABA) glutamate (Glu) glutamine (Gln) N-acetylaspartate (NAA) Choline-containing compounds (Cho) Creatine plus phophocreatine (total creatine: Cr) Myo-inositiol (Ins) Choline (Cho) Glucose (Glc) Lactate (Lac)<br>|
| Placebo Comparator: placebo + pregabalin<br> | Other: MR Spectroscopy<br>* During each MR Spectroscopy session, we will measure at regions of interest (rACC, both thalami, dominant DLPC) the levels of the following biochemical substances: gamma-aminobutyric acid (GABA) glutamate (Glu) glutamine (Gln) N-acetylaspartate (NAA) Choline-containing compounds (Cho) Creatine plus phophocreatine (total creatine: Cr) Myo-inositiol (Ins) Choline (Cho) Glucose (Glc) Lactate (Lac)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cerebral neurobiological effect of pregabaline as treatment for neuropathic pain | We will measure changes in neurotransmitter levels in the brain (gamma-aminobutyric acid (GABA) glutamate (Glu) glutamine (Gln) N-acetylaspartate (NAA) Choline-containing compounds (Cho) Creatine plus phophocreatine (total creatine: Cr) Myo-inositiol (Ins) Choline (Cho) Glucose (Glc) Lactate (Lac)) before and after treatment with pregabaline. Specific interest in ratio GABA/Gln and GABA/Glu: relationship between inhibitory and excitatory neurotransmittors | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cerebral neurobiological changes in relationship with dose dependent therapeutic effect of treatment with pregabaline | A possible dose dependent effect of treatment with Pregabalin on cerebral neurochemical changes (gamma-aminobutyric acid (GABA) glutamate (Glu) glutamine (Gln) N-acetylaspartate (NAA) Choline-containing compounds (Cho) Creatine plus phophocreatine (total creatine: Cr) Myo-inositiol (Ins) Choline (Cho) Glucose (Glc) Lactate (Lac)) and clinical effects (pain and quality of life scales) will be evaluated | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neuropathic pain, Diabetic Polyneuropathy