Efficacy of Xeomin for Migraines in Patients With Traumatic Brain Injuries vs. Anomalous Health Incidents

NCT ID: NCT07267819

Last Updated: 2025-12-05

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 60 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-08-05
• Study Completion Date: 2028-06-06

Brief Summary

This cohort study aims to compare the efficacy of Xeomin injections for migraine management in patients with a history of Traumatic Brain Injury (TBI) versus those with a history of Anomalous Health Incidents (AHI). The study will be conducted at the National Intrepid Center of Excellence (NICOE) in Bethesda, MD. The primary objective is to determine if Xeomin injections result in different outcomes for migraine management between TBI and AHI patients. This is a combined retrospective and prospective cohort study design. Patients scheduled for Xeomin treatments will be categorized into TBI and AHI groups. For the prospective cohort, participants will complete a baseline questionnaire, receive their scheduled Xeomin treatment, and participate in follow-up interviews at 4-6 weeks and 10-12 weeks post-treatment. For the retrospective cohort, similar information will be acquired from existing records. Statistical analysis will compare migraine characteristics and treatment responses between the two groups. All data will be de-identified to protect patient privacy.

Detailed Description

Headaches with migraine-like characteristics are a common sequelae of traumatic brain injury (TBI)¹-⁴ and Havana syndrome, otherwise known as anomalous health incidents (AHIs).⁵,⁶ In TBI patients, direct biomechanical forces lead to cellular injury and neuroinflammation, contributing to post-traumatic headaches. Specifically, the disruption of trigeminovascular pathways and the release of inflammatory mediators, such as calcitonin gene-related peptide (CGRP), are implicated in the pathophysiology of post-traumatic migraines. Furthermore, the presence of comorbid conditions, such as post-concussive syndrome, can exacerbate headache symptoms and complicate treatment strategies.⁷ Though the migraine-like headaches in patients with AHI are clinically similar to those seen in patients with mTBI, the absence of clear structural damage on conventional neuroimaging in many AHI cases raises questions about the underlying mechanisms.⁸,⁹ Theories involving unknown exposure and subsequent disruption of white matter function have been proposed. Some analyses suggest that the symptoms of AHI could result from the disruption of neuroimmune and neurotransmission mechanisms similar to those affected in patients with TBI.¹⁰,¹¹

Managing post-traumatic headaches involves a multidisciplinary approach including behavioral therapy, physical therapy, oral medications, injectable medications, and interventional procedures. Essentially, these headaches can be treated similarly to the primary headache disorder they resemble.¹² Thus, the post-traumatic migraine can be treated in the acute setting with triptans, NSAIDs, ergot alkaloids, antiemetics, and other therapeutics.¹³,¹⁴ For chronic management, options include beta-blockers, tricyclic antidepressants, CGRP-targeting agents, anti-seizure medications, and many other medications.¹²,¹⁵ Onabotulinum toxin A (OBA) and other medications in the class of botulinum toxins have been particularly effective at reducing the overall frequency and duration of migraines in patients with TBIs,¹⁶,¹⁷ as well as non-TBI-related migraines. OBA results in a blockade of neural stimulation by inhibiting the release of neurotransmitters at the presynaptic terminal.¹⁸,¹⁹ It's thought to reduce the exocytosis of pain mediators (substance P, CGRP) from sensory neurons by cleaving SNAP25.²⁰,²¹ This effect is temporary due to the formation of new synapses, thus patients have to return for repeat injections every 10-12 weeks. Additionally, the number of units of OBA can be optimized to the patient's level of pain during each treatment.

There is limited literature on managing post-AHI headache disorders, but recent experience indicates that using multidisciplinary approaches similar to those used for TBI-related headache disorders may be appropriate.⁶ OBA, and more specifically incobotulinum toxin A (Xeomin brand) has therefore been a commonly used treatment modality in these patient populations in the Military Health System. Many individuals with AHIs from other branches of the government are treated in the MHS though the Secretarial Designee program.

While AHI symptoms might share pathophysiological characteristics with TBIs, there's limited research on Xeomin injections' characteristics in TBI vs. AHI patients, such as treatment frequency and efficacy. This study aims to quantify these similarities and differences in migraine management with Xeomin, potentially improving our understanding of this treatment modality. Migraines can disrupt home, work, and social activities, and treatment can be especially difficult in AHI patients who face limited effective treatment options that are evidence-based, and unique diagnostic challenges. By comparing Xeomin's efficacy in both groups, this study could reveal crucial differences in treatment response, leading to more personalized and effective therapies that align with a holistic healthcare model in medicine. The findings could inform clinical guidelines and improve migraine management in TBI and AHI patients, ultimately reducing the healthcare burden. This research is essential for addressing AHI patients' unmet needs and advancing migraine treatment understanding.

Conditions

Migraine; Traumatic Brain Injury; Anomalous Health Incidents

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: OTHER

Study Groups

TBI Cohort

Patients with a history of Traumatic Brain Injury (TBI) receiving Xeomin treatments for migraine management. The anticipated number of participants is 40.

Xeomin (incobotulinumtoxinA)

Intervention Type: DRUG

Patients receive their scheduled Xeomin treatment as prescribed by their physician as part of their standard of care. The treatment protocol (dosage, injection sites, etc.) will be documented.

AHI Cohort

Patients with a history of Anomalous Health Incidents (AHI) receiving Xeomin treatments for migraine management. The anticipated number of participants is 20.

Xeomin (incobotulinumtoxinA)

Intervention Type: DRUG

Patients receive their scheduled Xeomin treatment as prescribed by their physician as part of their standard of care. The treatment protocol (dosage, injection sites, etc.) will be documented.

Interventions

Xeomin (incobotulinumtoxinA)

Patients receive their scheduled Xeomin treatment as prescribed by their physician as part of their standard of care. The treatment protocol (dosage, injection sites, etc.) will be documented.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• At least 18 years of age
• Able to provide written consent in English
• An employee of the US Government, or an adult family member of a US Government employee
• Have received Xeomin treatment to prevent migraine related to TBI or AHI at a Military Treatment Facility or other US Medical Facility
• Able to participate in at least 80% of the assessments
• A US Citizen and not a dual national of the country where you are currently located

Exclusion Criteria

• Prisoner
• Decisionally impaired and unable to provide informed consent
• Non-US citizen

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Uniformed Services University of the Health Sciences

FED

Sponsor Role: lead

Responsible Party

David Brody

Professor of Neurology, Uniformed Services University

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

National Intrepid Center of Excellence (NICOE)

Bethesda, Maryland, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

David L Brody, MD, PhD

Role: CONTACT

David.brody@usuhs.edu

314-537-6453

Facility Contacts

David L Brody, MD, PhD

Role: primary

david.brody@usuhs.edu

314-537-6453

Ananya Tripathi, MS

Role: backup

ananya.tripathi@usuhs.edu

443-876-0609

References

Walker WC, Seel RT, Curtiss G, Warden DL. Headache after moderate and severe traumatic brain injury: a longitudinal analysis. Arch Phys Med Rehabil. 2005 Sep;86(9):1793-800. doi: 10.1016/j.apmr.2004.12.042.

Reference Type: BACKGROUND

PMID: 16181945 (View on PubMed)

Hoffman JM, Lucas S, Dikmen S, Temkin N. Clinical Perspectives on Headache After Traumatic Brain Injury. PM R. 2020 Oct;12(10):967-974. doi: 10.1002/pmrj.12338. Epub 2020 Mar 2.

Reference Type: BACKGROUND

PMID: 32003524 (View on PubMed)

Klein SK, Brown CB, Ostrowski-Delahanty S, Bruckman D, Victorio MC. Identifying Migraine Phenotype Post Traumatic Headache (MPTH) to Guide Overall Recovery From Traumatic Brain Injury. J Child Neurol. 2022 Jun 3:8830738221100327. doi: 10.1177/08830738221100327. Online ahead of print.

Reference Type: BACKGROUND

PMID: 35656769 (View on PubMed)

Erickson JC. Treatment outcomes of chronic post-traumatic headaches after mild head trauma in US soldiers: an observational study. Headache. 2011 Jun;51(6):932-44. doi: 10.1111/j.1526-4610.2011.01909.x. Epub 2011 May 17.

Reference Type: BACKGROUND

PMID: 21592097 (View on PubMed)

Becker WJ. Acute Migraine Treatment. Continuum (Minneap Minn). 2015 Aug;21(4 Headache):953-72. doi: 10.1212/CON.0000000000000192.

Reference Type: BACKGROUND

PMID: 26252584 (View on PubMed)

Pringsheim T, Becker WJ. Triptans for symptomatic treatment of migraine headache. BMJ. 2014 Apr 7;348:g2285. doi: 10.1136/bmj.g2285. No abstract available.

Reference Type: BACKGROUND

PMID: 24711666 (View on PubMed)

Theeler B, Lucas S, Riechers RG 2nd, Ruff RL. Post-traumatic headaches in civilians and military personnel: a comparative, clinical review. Headache. 2013 Jun;53(6):881-900. doi: 10.1111/head.12123.

Reference Type: BACKGROUND

PMID: 23721236 (View on PubMed)

Chacko TP, Toole JT, Morris MC, Page J, Forsten RD, Barrett JP, Reinhard MJ, Brewster RC, Costanzo ME, Broderick G. A regulatory pathway model of neuropsychological disruption in Havana syndrome. Front Psychiatry. 2023 Oct 27;14:1180929. doi: 10.3389/fpsyt.2023.1180929. eCollection 2023.

Reference Type: BACKGROUND

PMID: 37965360 (View on PubMed)

Aristi G, Kamintsky L, Ross M, Bowen C, Calkin C, Friedman A, Hashmi JA. Symptoms reported by Canadians posted in Havana are linked with reduced white matter fibre density. Brain Commun. 2022 Mar 7;4(2):fcac053. doi: 10.1093/braincomms/fcac053. eCollection 2022.

Reference Type: BACKGROUND

PMID: 35505689 (View on PubMed)

Pierpaoli C, Nayak A, Hafiz R, Irfanoglu MO, Chen G, Taylor P, Hallett M, Hoa M, Pham D, Chou YY, Moses AD, van der Merwe AJ, Lippa SM, Brewer CC, Zalewski CK, Zampieri C, Turtzo LC, Shahim P, Chan L; NIH AHI Intramural Research Program Team; Moore B, Stamps L, Flynn S, Fontana J, Tata S, Lo J, Fernandez MA, Lori-Joseph A, Matsubara J, Goldberg J, Nguyen TD, Sasson N, Lely J, Smith B, King KA, Chisholm J, Christensen J, Magone MT, Cousineau-Krieger C, French LM, Yonter S, Attaripour S, Lai C. Neuroimaging Findings in US Government Personnel and Their Family Members Involved in Anomalous Health Incidents. JAMA. 2024 Apr 2;331(13):1122-1134. doi: 10.1001/jama.2024.2424.

Reference Type: BACKGROUND

PMID: 38497822 (View on PubMed)

Swanson RL 2nd, Hampton S, Green-McKenzie J, Diaz-Arrastia R, Grady MS, Verma R, Biester R, Duda D, Wolf RL, Smith DH. Neurological Manifestations Among US Government Personnel Reporting Directional Audible and Sensory Phenomena in Havana, Cuba. JAMA. 2018 Mar 20;319(11):1125-1133. doi: 10.1001/jama.2018.1742.

Reference Type: BACKGROUND

PMID: 29450484 (View on PubMed)

Ruff RL, Blake K. Pathophysiological links between traumatic brain injury and post-traumatic headaches. F1000Res. 2016 Aug 31;5:F1000 Faculty Rev-2116. doi: 10.12688/f1000research.9017.1. eCollection 2016.

Reference Type: BACKGROUND

PMID: 27635228 (View on PubMed)

National Academies of Sciences, Engineering, and Medicine; Division on Engineering and Physical Sciences; Health and Medicine Division; Standing Committee to Advise the Department of State on Unexplained Health Effects on U.S. Government Employees and Their Families at Overseas Embassies; Pavlin JA, Relman DA, editors. An Assessment of Illness in U.S. Government Employees and Their Families at Overseas Embassies. Washington (DC): National Academies Press (US); 2020 Dec 5. Available from http://www.ncbi.nlm.nih.gov/books/NBK566407/

Reference Type: BACKGROUND

PMID: 33411434 (View on PubMed)

Asadi-Pooya AA. Havana syndrome: a scoping review of the existing literature. Rev Environ Health. 2022 Aug 15;38(4):655-661. doi: 10.1515/reveh-2021-0182. Print 2023 Dec 15.

Reference Type: BACKGROUND

PMID: 35962646 (View on PubMed)

Ashina H, Porreca F, Anderson T, Amin FM, Ashina M, Schytz HW, Dodick DW. Post-traumatic headache: epidemiology and pathophysiological insights. Nat Rev Neurol. 2019 Oct;15(10):607-617. doi: 10.1038/s41582-019-0243-8. Epub 2019 Sep 16.

Reference Type: BACKGROUND

PMID: 31527806 (View on PubMed)

Lucas S, Hoffman JM, Bell KR, Dikmen S. A prospective study of prevalence and characterization of headache following mild traumatic brain injury. Cephalalgia. 2014 Feb;34(2):93-102. doi: 10.1177/0333102413499645. Epub 2013 Aug 6.

Reference Type: BACKGROUND

PMID: 23921798 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

USUHS.2025-154

Identifier Type: -

Identifier Source: org_study_id