Chronic MigrainePhase 4NCT07837570
Comparison of the Effectiveness of Greater Occipital Nerve and Supratrochlear Nerve Pulsed Radiofrequency Versus Botulinum Toxin Type A Injection in Chronic Migraine
A Phase 4 study testing OnabotulinumtoxinA and Ultrasound-guided pulsed radiofrequency (PRF) of the greater occipital nerve (GON) and supratrochlear nerve in people with Chronic Migraine, run by Assiut University.
Trial summary
Migraine is a common chronic neurovascular disorder ranked among the leading causes of disability worldwide, and its global burden has continued to rise over the past three decades, with prevalence increasing substantially between 1990 and 2021the global number of prevalent cases, incident cases, and DALYs for… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic Migraine
- What is being tested?
- OnabotulinumtoxinA and Ultrasound-guided pulsed radiofrequency (PRF) of the greater occipital nerve (GON) and supratrochlear nerve
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- No sites listed yet
- Study dates
- Oct 2026to Dec 2027
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age between 18 and 65 years, either sex.
- Diagnosis of chronic migraine according to the International Classification of Headache Disorders, 3rd edition (ICHD-3) criteria (headache occurring on ≥15 days/month for >3 months, with migrainous features on ≥8 days/month).
- Inadequate response, intolerance, or contraindication to at least one standard oral preventive medication (e.g., amitriptyline, propranolol, topiramate, flunarizine, valproate).
- Stable dose of any concurrent prophylactic medication for at least 4 weeks prior to enrolment, with no planned change during the study period.
- Willingness and ability to complete headache diaries and follow-up visits.
Who cannot join
- • Other primary headache disorders (tension-type headache, cluster headache, hemicrania continua) as the predominant headache type.
- Secondary headache due to an identifiable structural, infectious, vascular, or neoplastic cause (confirmed or suspected by history/imaging).
- Prior botulinum toxin injection or radiofrequency procedure for headache within the last 6 months.
- Known hypersensitivity or allergy to botulinum toxin or to local anesthetics.
- Pregnancy or lactation.
- Neuromuscular junction disorders (e.g., myasthenia gravis, Lambert-Eaton syndrome).
- Medication overuse headache not resolved prior to enrolment.
About this study
Migraine is a common chronic neurovascular disorder ranked among the leading causes of disability worldwide, and its global burden has continued to rise over the past three decades, with prevalence increasing substantially between 1990 and 2021the global number of prevalent cases, incident cases, and DALYs for migraine increased by 58%, 42%, and 58% respectively from 1990 to 2021 (1). In 2021, migraine affected an estimated 1.2 billion people globally, and although tension-type headache was more prevalent, migraine caused greater disability (2). Chronic migraine, defined as headache occurring on 15 or more days per month for more than three months, with migrainous features on at least 8 days, represents a particularly disabling subtype that is frequently refractory to standard pharmacological prophylaxis (3). Pharmacologic treatment of chronic migraine often has limited efficacy, prompting growing interest in interventional and peripheral neuromodulatory approaches (4).
OnabotulinumtoxinA is currently the only FDA-approved interventional prophylactic therapy for chronic migraine, with efficacy established by class-one evidence from the PREEMPT clinical program (5). Although onabotulinumtoxinA is traditionally known for inhibiting muscle contraction, its efficacy in chronic migraine is now attributed to inhibition of SNARE-mediated vesicle trafficking in sensory as well as motor nerve terminals (6). However, treatment with onabotulinumtoxinA, while effective, must be repeated every three months for sustained relief and can impose a significant financial burden on patients (7), which has driven exploration of alternative peripheral procedures targeting the same pericranial sensory nerve distribution.
Read more
Greater occipital nerve block and PRF have shown efficacy in reducing migraine frequency, intensity, and duration, with pulsed radiofrequency treatment thought to reduce conduction in nociceptive fibers through a neuromodulatory, non-neurodestructive mechanism (8). Randomized data comparing GON block with GON-PRF found that VAS pain scores were significantly lower in the PRF group than the GON block group at six months follow-up (9), and longer-term cohort data have shown durable benefit of GON-targeted radiofrequency techniques over twelve months of follow-up (10). Beyond the occipital nerve, radiofrequency ablation of pericranial nerves including the supratrochlear and supraorbital nerves has emerged as a promising option for headache conditions refractory to pharmacologic treatment, with a favorable and largely self-limited side-effect profile (7). Case reports have further demonstrated good therapeutic response to PRF in patients whose chronic migraine remained refractory even after botulinum toxin injection.
Despite this growing evidence base, direct head-to-head comparisons between combined GON-supratrochlear nerve PRF and onabotulinumtoxinA injection, the two leading peripheral interventional strategies covering the trigeminal and occipital sensory distribution, remain scarce. Given the cost, repeated dosing requirement, and resource burden associated with botulinum toxin therapy, and the emerging durability data for PRF, a direct comparative study is warranted to determine which modality offers superior and more sustained efficacy, better safety, and greater cost-effectiveness for patients with chronic migraine.
- Conditions
- Chronic Migraine
- Being tested
- OnabotulinumtoxinA, Ultrasound-guided pulsed radiofrequency (PRF) of the greater occipital nerve (GON) and supratrochlear nerve
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OnabotulinumtoxinADrug
patients will recive OnabotulinumtoxinA (Botulinum Toxin Type A) injection according to the PREEMPT injection protocol.
Ultrasound-guided pulsed radiofrequency (PRF) of the greater occipital nerve (GON) and supratrochlear nerveProcedure or surgery
patients will recive Ultrasound-guided pulsed radiofrequency (PRF) of the greater occipital nerve (GON) and supratrochlear nerve
| Study group | Role | What they receive |
|---|---|---|
| Group A | Active comparator | Ultrasound-guided pulsed radiofrequency (PRF) of the greater occipital nerve (GON) and supratrochlear nerve Receives: Procedure: Ultrasound-guided pulsed radiofrequency (PRF) of the greater occipital nerve (GON) and supratrochlear nerve |
| Group B | Active comparator | OnabotulinumtoxinA (Botulinum Toxin Type A) injection according to the PREEMPT injection protocol. Receives: Drug: OnabotulinumtoxinA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the mean number of monthly migraine days
Change in the mean number of monthly migraine days (MMD) from baseline to 12 weeks and 24 weeks post-intervention
Measured: 24 weeks post-intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2026
- Study startOct 2026 (estimated)
- Primary completionOct 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic MigraineStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hussein Abd Elrahim Hussein Mohamed, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07837570
- Sponsor's protocol ID
- Radiofrequency vs Botulinum
- Status last verified
- Sep 2026
- First submitted
- 18 Sep 2026
- Last updated
- 23 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No