BOTOX® vs. XEOMIN® for Chronic Migraine

Official title

A Randomized, Double-Blind Study on the Effect of OnabotulinumtoxinA (BOTOX®) vs. IncobotulinumtoxinA (XEOMIN®) Botulinum Toxin in Adults With Chronic Migraine

Overview

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.

Interventions

• Drug IncobotulinumtoxinA (XEOMIN®)
  IncobotulinumtoxinA (XEOMIN®) is injected into specific targets at two different time points. Changes in chronic migraine frequency and duration are recorded and compared.
• Drug OnabotulinumtoxinA (BOTOX®)
  OnabotulinumtoxinA (BOTOX®) is injected into specific targets at two different time points. Changes in chronic migraine frequency and duration are recorded and compared.

Primary outcome measures

• Headache days per month [Time frame: 24 weeks + Baseline]

Secondary outcome measures (2)

• Differences in headache impact [Time frame: 24 weeks vs. Baseline]
• Differences in Health-Related Quality of Life [Time frame: 24 weeks vs. Baseline]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 1 center

• Naval Medical Center Camp Lejeune — Jacksonville

Publications

• Burstein R, Noseda R, Borsook D. Migraine: multiple processes, complex pathophysiology. J Neurosci. 2015 Apr 29;35(17):6619-29. doi: 10.1523/JNEUROSCI.0373-15.2015. PMID 25926442
• Sandrini G, De Icco R, Tassorelli C, Smania N, Tamburin S. Botulinum neurotoxin type A for the treatment of pain: not just in migraine and trigeminal neuralgia. J Headache Pain. 2017 Dec;18(1):38. doi: 10.1186/s10194-017-0744-z. Epub 2017 Mar 21. PMID 28324318
• May A, Schulte LH. Chronic migraine: risk factors, mechanisms and treatment. Nat Rev Neurol. 2016 Aug;12(8):455-64. doi: 10.1038/nrneurol.2016.93. Epub 2016 Jul 8. PMID 27389092
• Schwedt TJ. Chronic migraine. BMJ. 2014 Mar 24;348:g1416. doi: 10.1136/bmj.g1416. PMID 24662044
• Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013 Jul;33(9):629-808. doi: 10.1177/0333102413485658. No abstract available. PMID 23771276
• Do TP, Hvedstrup J, Schytz HW. Botulinum toxin: A review of the mode of action in migraine. Acta Neurol Scand. 2018 May;137(5):442-451. doi: 10.1111/ane.12906. Epub 2018 Feb 6. PMID 29405250
• Carruthers A, Carruthers J. Botulinum toxin products overview. Skin Therapy Lett. 2008 Jul-Aug;13(6):1-4. PMID 18806905
• Frevert J, Dressler D. Complexing proteins in botulinum toxin type A drugs: a help or a hindrance? Biologics. 2010 Dec 9;4:325-32. doi: 10.2147/BTT.S14902. PMID 21209727

Identifiers

NCT: NCT05598723 · NMCCL.2022.0029

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗