Evaluation of Lamotrigine on Neuropathic Facial Pain Using fMRI

Study Overview
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Brief Summary
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The aim of this project is to evaluate the effects of the anticonvulsant drug lamotrigine (trade name Lamictal) on neuropathic facial pain or neuralgia using functional magnetic resonance imaging (fMRI).

Detailed Description
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Currently there are no pharmacological agents that can control neuropathic pain akin to the efficacy of antibiotics for bacterial infection. All current neuropathic pain drugs have approximately the same efficacy of less than 30% in controlled trials, and many of these drugs do not have known mechanisms of action. fMRI studies may provide insight into how brain circuitry is altered by chronic pain, and how these drugs act on altered circuitry. The trigeminal system in particular offers unique advantages for studying such alterations, including a large central representation and high degree of somatotopy. The administration of lamotrigine to neuropathic pain patients in conjunction with fMRI will allow us to compare subjective ratings of pain with objective measures of neural activity during increased conditions of allodynia/hyperalgesia.

Official Title
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Evaluation of Lamotrigine on Neuropathic Facial Pain Using fMRI

Conditions
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Facial Neuropathy

Intervention / Treatment
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* Drug: Lamotrigine
* Drug: Placebo (for Lamotrigine)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-60 years of age Right-handed non-smokers Diagnosed with facial pain Continuous pain for more than 3 months Spontaneous pain greater than 3 of 10 Allodynia to brush greater than 5 of 10 Exclusion Criteria: Medications Depression Significant medical problems Claustrophobia Abnormal EKG Significant drug or alcohol history Positive drug screen Weight greater than 285 lbs History of allergy to anticonvulsants Tattoos with metallic ink on upper body Any neurostimulator devices, or metal cochlear, ocular, or cardiac implants or other metal near vital areas Exposure to shrapnel or metal filings Other metallic surgical hardware

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lamotrigine to Placebo Crossover<br>The drug lamotrigine will be given for 9 weeks prior to imaging session 1. A rescue drug, Gabapentin, will be provided for pain control. Patients will taper off the Gabapentin 2 weeks before each scan date. After a taper and washout, placebo (cross over) will be administered. At the end of the trial (after imaging session 2), a taper for placebo will be given. Patients will be required to maintain a pain diary during the study, documenting the perceived effects of the drug on the severity of their pain and keeping track of their subjective pain ratings day to day. Patients will also complete the McGill Pain Questionnaire at each visit. | Drug: Lamotrigine<br>* : 25mg and 50mg tablets<br>* Other names: LAM;|
| Active Comparator: Placebo to Lamotrigine Crossover<br>The placebo will be given for 9 weeks prior to imaging session 1. A rescue drug, Gabapentin, will be provided for pain control. Patients will taper off the Gabapentin 2 weeks before each scan date. After a taper and washout, the drug lamotrigine (cross over) will be administered. At the end of the trial (after imaging session 2), a taper for drug will be given. Patients will be required to maintain a pain diary during the study, documenting the perceived effects of the drug on the severity of their pain and keeping track of their subjective pain ratings day to day. Patients will also complete the McGill Pain Questionnaire at each visit. | Drug: Placebo (for Lamotrigine)<br>* Sugar pill manufactured to mimic Lamotrigine tablets<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Oxygenation Level-dependent (BOLD) Changes in Neural Pain Circuitry Following Treatment With Lamotrigine During Experimentally Induced Pain States | fMRI scans acquired Stimuli Type: Brush Stimulation Regions: Face (V2) Right and Left Sides Rating: Pain/ unpleasantness fMRI scans acquired Stimuli Type: Cold, threshold -1°C Stimulation Regions: Face (V2) Right and Left Sides Rating: Pain/ unpleasantness **Extra time allotted for probe repositioning** fMRI scans acquired Stimuli Type: Heat, threshold +1°C Stimulation Regions: Face (V2) Right and Left Sides Rating: Pain/ unpleasantness **Extra time allotted for probe repositioning** Cortical, subcortical, and brain stem sensory regions Z-scores Increase or decrease in activation as affected by the drug | Week 10 during scanning session | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective Ratings of Pain During Magnetic Resonance Scanning | Quantitative Sensory Testing (QST) Stimuli Type: Heat, Cold, Brush Stimulation Regions: Face Affected and contralateral Unaffected mirror area Rating: Pain/ unpleasantness Stimuli Type: Cold, threshold -1°C Stimulation Regions: Face Affected and contralateral Unaffected mirror area Rating: Pain/ unpleasantness Stimuli Type: Heat, threshold +1°C Stimulation Regions: Face Affected and contralateral Unaffected mirror area Rating: Pain/ unpleasantness Ratings on a likert scale of 0-10 with 0 being defined as no pain and 10 being defined as worst possible pain | week 10 (during the scan) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pain, neuropathic, face, trigeminal