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

November 24, 2025 updated by: David Brody, Uniformed Services University of the Health Sciences

The Efficacy of Xeomin as a Prophylactic Therapy for Migraine in Patients With Traumatic Brain Injuries (TBIs) Versus Anomalous Health Incidents (AHIs)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Estimated)

60

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20814
        • Recruiting
        • National Intrepid Center of Excellence (NICOE)
        • Contact:
        • Contact:
        • Principal Investigator:
          • David L Brody, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Employees of the US Government, or adult family members of US Government employees, receiving Xeomin treatment for migraine headache following either TBI or AHI.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
TBI Cohort
Patients with a history of Traumatic Brain Injury (TBI) receiving Xeomin treatments for migraine management. The anticipated number of participants is 40.
Drug: 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.
AHI Cohort
Patients with a history of Anomalous Health Incidents (AHI) receiving Xeomin treatments for migraine management. The anticipated number of participants is 20.
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Change in Migraine Headache Intensity from Baseline to Peak Effect (4 weeks post-treatment) and to wearing off (12 weeks post-treatment).
Time Frame: Baseline, 4 weeks post-treatment, and 12 weeks post-treatment.
Comparison between TBI and AHI groups in the percent change of migraine headache intensity. Intensity is assessed using a 0-10 Numeric Rating Scale (NRS) in response to the question, "How painful were the migraine headaches typically at their worst (0-10)?". For this scale, 0 indicates 'no pain' and 10 indicates the 'worst imaginable pain,' where a higher score signifies a worse outcome. The change is measured from baseline ("Before you started Xeomin treatments") to peak effect ("When your Xeomin was at its peak effect").
Baseline, 4 weeks post-treatment, and 12 weeks post-treatment.
Percent Change in Migraine Headache Frequency from Baseline to Peak Effect (4 weeks post-treatment) and to wearing off (12 weeks post-treatment).
Time Frame: Baseline, 4 weeks post-treatment, and 12 weeks post-treatment.
Comparison between TBI and AHI groups in the percent change of migraine headache frequency. Frequency is defined as the total number of migraine headaches in a typical week, as reported on a patient questionnaire. The minimum value for this count is 0, and a higher number indicates a worse outcome. The change is measured from baseline to the time of the treatment's peak effects.
Baseline, 4 weeks post-treatment, and 12 weeks post-treatment.
Percent Change in Headache Impact Test (HIT-6) Score from Baseline to Peak Effect (4 weeks post-treatment) and to wearing off (12 weeks post-treatment).
Time Frame: Baseline, 4 weeks post-treatment, and 12 weeks post-treatment.
Comparison between TBI and AHI groups in the percent change in the Headache Impact Test (HIT-6) score. The HIT-6 is a 6-item questionnaire assessing the impact of headaches on daily life. Patient responses ("Never," "Rarely," "Sometimes," "Very Often," "Always") are converted to a numerical score. The total score ranges from 36 to 78, where a higher score indicates a more severe headache impact, representing a worse outcome. The change is measured from baseline to the time of the treatment's peak effects
Baseline, 4 weeks post-treatment, and 12 weeks post-treatment.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Xeomin Effectiveness.
Time Frame: Up to 12 weeks post-treatment.
Comparison between TBI and AHI groups regarding the timeline of Xeomin effectiveness, including time to onset of effects and duration of benefits.
Up to 12 weeks post-treatment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Uniformed Services University of the Health Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 5, 2025

Primary Completion (Estimated)

June 6, 2028

Study Completion (Estimated)

June 6, 2028

Study Registration Dates

First Submitted

September 11, 2025

First Submitted That Met QC Criteria

November 24, 2025

First Posted (Actual)

December 5, 2025

Study Record Updates

Last Update Posted (Actual)

December 5, 2025

Last Update Submitted That Met QC Criteria

November 24, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • USUHS.2025-154

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The study protocol specifies that there are no data sharing or data use agreements in place for this research. The data collected is intended for internal analysis by authorized research personnel only. While de-identified, aggregate results may be published, the consent form assures participants that their individual data will not be shared in any way that would identify them.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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