Incobotulinum Toxin for the Treatment of Trigeminal Neuralgia

Study Overview
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Brief Summary
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IncobotulinumtoxinA (Xeomin®) is a neurotoxin which inhibits the release of certain chemicals at the nerve terminals. It blocks cholinergic transmission at the neuromuscular junction by inhibiting the release of acetylcholine from motor neurons. In addition it blocks the release of Substance P (SP) and Calcitonin Gene Related Peptide (CGRP) from C fibers involved in pain perception. This study is designed to see if Xeomin® is superior to placebo in the treatment of medically refractory trigeminal neuralgia (TN). Subjects will be asked to maintain an attack diary throughout the study. They will also be asked to attend 4 office visits; Visit 1- Screening Visit, Visit 2- Injection Visit, Visit 3- Follow-Up Visit and Visit 4- Final Visit. At the end of the study the active (Xeomin®) and placebo groups will be compared to see if one group had better relief than the other.

Detailed Description
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This is a randomized, double-blind, placebo-controlled, add-on therapy study. Up to 70 eligible subjects with medically refractory TN will be screened to enroll forty subjects; twenty will be randomized to the active medication group IncobotulinumtoxinA (Xeomin) and twenty to the placebo group (0.9% Normal Saline Solution). Using a daily diary, all subjects will document their overall pain level and attack frequency and intensity for four weeks. After the four week baseline period, subjects will undergo initial injections (IncobotulinumtoxinA [Xeomin] or placebo). Subjects will remain on a consistent dose of their previously prescribed medications throughout the study. The primary outcome will be the difference in decrease in mean number of attacks of at least 4/10 intensity between the active and placebo groups. Secondary outcome measures will be frequency and average intensity of daily pain attacks. Subject Global Assessment, Beck Depression Inventory II (BDI-II), Short Form-36 (SF-36) Health Surveys, and visual analog scale (VAS), will also be assessed.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Add-on Therapy Study of Xeomin (Incobotulinumtoxina) Versus Placebo in the Treatment of Trigeminal Neuralgia

Conditions
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Trigeminal Neuralgia

Intervention / Treatment
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* Biological: Incobotulinumtoxina
* Other: Placebo Comparator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:Inclusion Criteria Age 18 - 75 yrs Male or non-pregnant/non-lactating female Subjects must have a mean attack frequency of at least 3 episodes/day of 4/10 pain Use of adequate birth-control measures as determined by investigator for females of child-bearing potential Diagnosis of Classical trigeminal neuralgia (TN) using International Classification of Headache Disorders (ICHD-2) criteria (see Appendix A in Protocol) Subjects have given written informed consent prior to entering study Subjects on a stable dose of concomitant preventive medications for treatment of TN for at least 4 weeks prior to study entry and throughout the 12 week observation period Subjects who require rescue analgesic medication during the study will be allowed to use their current (pre-study) opioid and/or non opioid analgesics as clinically indicated (e.g., non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, cyclooxygenase-2 (COX-2) inhibitors, topical analgesics). Subjects will be prohibited from initiating any therapy with a new preventive medication throughout the remainder of the study. Subject must be willing and able to abstain from initiating an alternative therapy (e.g., acupuncture, massage or physical therapy) for pain relief during the study. (NOTE: subjects who are currently using alternative therapy for pain relief can be enrolled if they are willing and able to maintain such therapy stable throughout the study.) - Exclusion Criteria:Exclusion Criteria Symptomatic TN Serious hepatic, respiratory, hematologic, cardiovascular or renal condition Neurologic pain other than TN, with the exception of occasional migraine or tension-type headaches. (<4 headaches per month; < 10 headache days/month) Psychiatric or medical condition that might compromise participation in study, as determined by the investigator Administration of any investigational drug within 30 days prior to screening History of substance abuse/alcoholism

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Incobotulinumtoxina<br>Xeomin 25-100 units injected to chosen area one time. | Biological: Incobotulinumtoxina<br>* Incobotulinumtoxina (Xeomin) is botulinum toxin type A and is administered via intramuscular injection.<br>* Other names: Xeomin;|
| Placebo Comparator: Placebo Comparator<br>Placebo Comparator is 1-2 ml normal saline solution injected to chosen area one time. | Other: Placebo Comparator<br>* Normal saline is sterile sodium chloride without and preservatives.<br>* Other names: Normal Saline, sodium chloride, placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean Number of Headache Attacks Reported in Active and Placebo Group | Mean daily number of attacks during baseline period (30 days) will be compared to mean daily number of attacks for baseline and 84 days as recorded in patient diary. | 84 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean Pain Intensity of Active and Placebo Group | Mean of the daily pain intensity as measured on a 0-10 pain scale where 0 = no pain and 10 is the worst pain reported on paper diary from baseline and 84 days | 84 days |