BOTOX® vs. XEOMIN® for Chronic Migraine

Chronic Migraine Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05598723
• Other study ID #: NMCCL.2022.0029
• Status: Recruiting
• Phase: Phase 3
• Start date: February 24, 2023
• Est. completion date: August 24, 2025

Study information

• Verified date: November 2023
• Source: Naval Medical Center Camp Lejeune
• Contact: Kathleen T Tilman, MD
• Phone: ?(910) 226-2258?
• Email: kathleen.t.tilman.mil[@]health.mil
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 128
• Est. completion date: August 24, 2025
• Est. primary completion date: February 24, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 89 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Migraine
• Migraine Disorders

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Naval Medical Center Camp Lejeune	Jacksonville	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Naval Medical Center Camp Lejeune

Country where clinical trial is conducted

United States, 

References & Publications (22)

Aurora SK, Dodick DW, Turkel CC, DeGryse RE, Silberstein SD, Lipton RB, Diener HC, Brin MF; PREEMPT 1 Chronic Migraine Study Group. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial. Cephalalgia. 2010 Jul;30(7):793-803. doi: 10.1177/0333102410364676. Epub 2010 Mar 17. — View Citation

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Diener HC, Dodick DW, Aurora SK, Turkel CC, DeGryse RE, Lipton RB, Silberstein SD, Brin MF; PREEMPT 2 Chronic Migraine Study Group. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia. 2010 Jul;30(7):804-14. doi: 10.1177/0333102410364677. Epub 2010 Mar 17. — View Citation

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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. — View Citation

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Kawata AK, Shah N, Poon JL, Shaffer S, Sapra S, Wilcox TK, Shah S, Tepper SJ, Dodick DW, Lipton RB. Understanding the migraine treatment landscape prior to the introduction of calcitonin gene-related peptide inhibitors: Results from the Assessment of TolerabiliTy and Effectiveness in MigrAINe Patients using Preventive Treatment (ATTAIN) study. Headache. 2021 Mar;61(3):438-454. doi: 10.1111/head.14053. Epub 2021 Feb 16. — View Citation

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Rendas-Baum R, Bloudek LM, Maglinte GA, Varon SF. The psychometric properties of the Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ) in chronic migraine patients. Qual Life Res. 2013 Jun;22(5):1123-33. doi: 10.1007/s11136-012-0230-7. Epub 2012 Jul 15. — View Citation

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. — View Citation

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Stark C, Stark R, Limberg N, Rodrigues J, Cordato D, Schwartz R, Jukic R. Real-world effectiveness of onabotulinumtoxinA treatment for the prevention of headaches in adults with chronic migraine in Australia: a retrospective study. J Headache Pain. 2019 Jul 15;20(1):81. doi: 10.1186/s10194-019-1030-z. — View Citation

Wilderman I, Tallarigo D, Pugacheva-Zingerman O. A Qualitative Study to Explore Patient Perspectives of Prophylactic Treatment with OnabotulinumtoxinA for Chronic Migraine. Pain Ther. 2021 Dec;10(2):1523-1536. doi: 10.1007/s40122-021-00316-2. Epub 2021 Sep 14. — View Citation

Yiannakopoulou E. Serious and long-term adverse events associated with the therapeutic and cosmetic use of botulinum toxin. Pharmacology. 2015;95(1-2):65-9. doi: 10.1159/000370245. Epub 2015 Jan 21. — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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