BOTOX® vs. XEOMIN® for Chronic Migraine

Study Overview
=================
Brief Summary
-----------------
Chronic migraine (CM) is a disabling disorder that sidelines active duty personnel and diminishes their quality of life. It affects 1.3% to 2.4% of the general population. These numbers increase in active duty personnel, especially those returning from deployment, as well as in veterans. Furthermore, these numbers are 4-5 times higher in military members who experienced at least one mild traumatic brain injury. CM leads to impaired cognition and poor decision-making. These impairments on critical active duty tasks could have a significant impact on task readiness and military performance. Therefore, CM presents a challenge for the return to duty mission. Currently, onabotulinumtoxinA is the only FDA-approved prophylactic treatment for CM; however, this treatment requires refrigeration, to which there is little access for the forward-deployed members who have limited access to adequate storage for this treatment. Therefore, it is imperative to identify a CM treatment that does not require refrigeration. Furthermore, in light of the ongoing COVID-19 pandemic and resulting international shortages in critical medication production and delivery, it is imperative to identify more than one treatment option for the management of CM. In this study, we will test the efficacy of incobotulinumtoxinA, a neurotoxin that, unlike onabotulinumtoxinA, does not require refrigeration, but is an effective off-label alternative for the treatment of migraine. OnabotulinumtoxinA and incobotulinumtoxinA are comparable in strength, with a conversion ratio of 1:1.

Detailed Description
-----------------
One hundred and twenty-eight male and female active duty personnel, adult dependent and retiree patients from the Navy Medical Center at Camp Lejeune who meet the International Classification of Headache Disorders 3rd Edition (ICHD-3) criteria of ≥15 headache days per month lasting 4 hours or longer will participate in the trial. Subjects will be group-allocated randomly, 64 to onabotulinumtoxinA and 64 to incobotulinumtoxinA. Injections of either treatment will occur twice, 12 weeks apart, in the head and neck regions. The primary treatment efficacy measurement will be the mean change in headache days 12 to 24 weeks post-treatment. Participants will complete an electronic diary to report headache days, their severity, and adverse effects or unforeseen events. A baseline will be established four weeks prior to the first botulinumtoxinA (Botox or Xeomin) administration using the number of headache days and two questionnaires, Headache Impact Test-6 (HIT-6) and the Migraine Specific Quality (MSQ) Questionnaire, which assess headache impact and Health-Related Quality of Life (HRQOL), respectively. These questionnaires will also be administered at weeks 12 and 24 of the study. The baseline, 12-, and 24-week analysis will be performed using a time vs. treatment repeated measures analysis of variance for headache days. Secondary outcomes (total scores of both the HIT-6 and MSQ) will be analyzed similarly.

Official Title
-----------------
Single Center Study on the Sustained Effect of OnabotulinumtoxinA (BOTOX®) vs. IncobotulinumtoxinA (XEOMIN®) Botulinum Toxin in Adults With Chronic Migraine

Conditions
-----------------
Chronic Migraine

Intervention / Treatment
-----------------
* Drug: IncobotulinumtoxinA (XEOMIN®)
* Drug: OnabotulinumtoxinA (BOTOX®)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Between ages of 18-89 15 or more headaches days experienced per month lasting 4 hours or longer Department of Defense (DoD) Beneficiary/TriCare Eligible Failure, contraindication or intolerance to two migraine medications from two different classes. Able to provide informed consent and be able to read and write English. Able to read, comprehend, and complete the assessment and diary Women must provide a negative urine pregnancy test Exclusion Criteria: Currently pregnant, breastfeeding, or planning to become pregnant Allergic to botulinum toxin or to any of the ingredients of the medication Has myasthenia gravis, amyotrophic lateral sclerosis, or Eaton Lambert syndrome, mitochondrial disease, fibromyalgia, any temporomandibular disfunction, or any other significant disease that might interfere with neuromuscular function. Uncontrolled epilepsy defined as more than 1 generalized seizure in any month within the 3 months prior to the day 0 visit Those on oral anticoagulation Previous botulinum toxin treatment on the cephalic/upper lumbar region within 6 months for any indication Localized infections on face, neck or on antibiotics for areas in this region Unable to attend study follow up visits for any reason (i.e. Training, deployment, or PCS) Use of any prophylactic headache medication between -4 weeks and week 0 visits Any person taking chronic pain medication for a chronic indication Any diagnosed psychiatric condition which would prohibit a participant from completing the trial in its totality.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 89 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A randomized, double blind, prospective, parallel-group study (non-inferiority trial)
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: OnabotulinumtoxinA (BOTOX®)<br>OnabotulinumtoxinA (BOTOX®) Group: Administration consists of 31 injections (5 onabotulinumtoxinA (BOTOX®) units per injection, for a total of 155units) in the head and neck at two time points (12 weeks apart). Injection sites include the forehead, temples, back of the head, upper neck, and the junction of the shoulder and the neck. A very small (e.g., 30-gauge), very sharp needle will be used to perform the injections. | Drug: OnabotulinumtoxinA (BOTOX®)<br>* OnabotulinumtoxinA (BOTOX®) is injected into specific targets at two different time points. Changes in chronic migraine frequency and duration are recorded and compared.<br>* Other names: Botox;|
| Experimental: IncobotulinumtoxinA (XEOMIN®)<br>IncobotulinumtoxinA (XEOMIN®) Group: Administration consists of 31 injections (5 incobotulinumtoxinA (XEOMIN®) units per injection, for a total of 155 units) in the head and neck at two time points (12 weeks apart). Injection sites include the forehead, temples, back of the head, upper neck, and the junction of the shoulder and the neck. A very small (e.g., 30-gauge), very sharp needle will be used to perform the injections. | Drug: IncobotulinumtoxinA (XEOMIN®)<br>* IncobotulinumtoxinA (XEOMIN®) is injected into specific targets at two different time points. Changes in chronic migraine frequency and duration are recorded and compared.<br>* Other names: Xeomin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Headache days per month | To compare the difference in headache days per month (incobotulinumtoxinA (XEOMIN®) relative to onabotulinumtoxinA (BOTOX®)) at the end of treatment period (24 weeks). | 24 weeks + Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in headache impact | Assessed using the Headache Impact Test-6 (HIT-6): mean change from baseline will be reported. HIT-6 score ranges between 36 and 78, with larger scores reflecting greater impact. | 24 weeks vs. Baseline | 
| Differences in Health-Related Quality of Life | Assessed using the Migraine Specific Quality (MSQ) Questionnaire: mean change from baseline will be reported. MSQ score ranges between 0-100 scale, with higher scores signifying better health-related quality of life. | 24 weeks vs. Baseline | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Botox, Xeomin, onabotulinumtoxinA, incobotulinumtoxinA, Botulinum Toxin, refrigeration, HIT-6