Prospective, Multi-Center Evaluation of the Efficacy of Peripheral Trigger Decompression Surgery for Migraine Headaches

Study Overview
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Brief Summary
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According to the peripheral trigger theory of migraine headaches, nociceptive inputs from irritated or compressed cranial nerve branches can lead to neurovascular changes in the brain that cause migraine headaches. Advanced treatments aimed at deactivating the peripheral trigger points can be administered to patients who have failed medical management of migraines. Those accepted advanced treatments include botulinum toxin A injection in order to temporarily paralyze muscles causing nerve compression, and surgery to release those compression points permanently. An advantage of surgery is the ability to release non-muscular causes of nerve compression, such as fascial bands or intersecting arteries. Botulinum toxin A injection into trigger sites has been shown in multiple studies to be effective at reducing the frequency and severity of migraine headaches, and is a very commonly administered treatment for refractory migraines. It is approved by the FDA for the treatment of chronic migraines. Similarly, surgical decompression of trigger sites has previously been shown to have superior clinical outcomes to medical management, through a randomized, blinded controlled-trial performed at Case Western Reserve in 2009. Patients either received actual decompression of the trigger sites, or sham surgery (exposure and visualization of the trigger sites, without decompression). At one-year follow-up, the group who underwent actual surgery demonstrated a statistically higher proportion with significant improvement in their migraines (83.7% vs. 57.7%, p=0.014), and with complete elimination of their migraines (57.1% vs. 3.8%, p<0.001). Several other reports have confirmed the good clinical outcomes of surgery demonstrated in this trial, and surgical decompression is now commonly performed by several surgeons around the United States. Prognostic factors predicting the success of surgical decompression in migraine headache treatment include older age of migraine onset, visual symptoms/aura, and 4-site decompression. Factors predicting failure of surgery include excessive operative blood loss, and surgery on only one or two trigger sites. One criticism of the studies on peripheral trigger decompression surgery for migraines has been that most of the results have originated from the same institution (Case Western Reserve), and from the same author (Guyuron). While several studies at other institutions have demonstrated positive outcomes of peripheral trigger decompression, these have only included a small number of patients. In addition, the sham surgery randomized-controlled trial has been criticized for not clarifying any prior treatments that patients had undergone before peripheral trigger deactivation, and for not showing how medication use patterns changed after surgery. Another criticism of that study was the fact that patients were examined by neurologists before the study but not after the study, and that surgery was performed on some patients with episodic migraines, who are known to not benefit from botulinum toxin. It is unclear what migraine types are most likely to benefit from surgical decompression. The investigators' goal is to perform a multi-center, prospective trial to demonstrate the effectiveness of peripheral trigger decompression in the treatment of migraine headaches, which would address the criticisms mentioned above. The main aim is to demonstrate that the positive results demonstrated by Guyuron et al are reproducible at other institutions and by other surgeons using similar techniques on different patient populations.

Conditions
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Migraine Headaches

Intervention / Treatment
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* Drug: Botulinum Toxin Type A
* Procedure: Surgery
* Other: Daily headache diary
* Other: Migraine Disability Assessment Test (MIDAS)
* Other: Migraine Work and Productivity Loss Questionnaire (MWPLQ)
* Other: Migraine-Specific Quality of Life Questionnaire (MSQ)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with migraines related to a trigger site at the location of a branch of a cranial nerve (frontal, temporal, occipital) Patients with chronic migraine (≥15 days per month) as dictated by the FDA indication for botulinum, and as diagnosed by a board-certified neurologist Patients with episodic migraines Those patients are included because there is no consensus whether surgical decompression is effective for chronic migraines only, or for chronic and episodic migraines. One of the goals of this trial is to determine this. Patients who respond to diagnostic botulinum toxin injection or to a diagnostic anesthetic block Patients who have failed 2 of 3 classes of preventative migraine medications Exclusion Criteria: Patients deemed by the authors or the neurologist to not have migraine headaches, but an alternative diagnosis Patients with systemic conditions that make them poor candidates for surgery (coronary artery disease, uncontrolled diabetes mellitus, etc…) Patients with migraines related to inferior turbinate hypertrophy or septal deviation Patients with a frontal, temporal or occipital trigger point who do not respond to a diagnostic botulinum toxin injection or to a diagnostic anesthetic block Hypersensitivity to any botulinum toxin preparation or to any of the components in the formulation Infection at the proposed injection site for botulinum Patients with trigger points at minor trigger sites (lesser occipital nerve, third occipital nerve)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Botulinum toxin<br>Patients in this arm will receive botulinum toxin for migraine headaches | Drug: Botulinum Toxin Type A<br> <br> Other: Daily headache diary<br> <br> Other: Migraine Disability Assessment Test (MIDAS)<br> <br> Other: Migraine Work and Productivity Loss Questionnaire (MWPLQ)<br> <br> Other: Migraine-Specific Quality of Life Questionnaire (MSQ)<br> <br> |
| Experimental: Surgery<br>Patients in this arm will receive surgery for migraine headaches | Procedure: Surgery<br> <br> Other: Daily headache diary<br> <br> Other: Migraine Disability Assessment Test (MIDAS)<br> <br> Other: Migraine Work and Productivity Loss Questionnaire (MWPLQ)<br> <br> Other: Migraine-Specific Quality of Life Questionnaire (MSQ)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Migraine Headache Index (MHI) at 3 months |  | 3 months postoperatively | 
| Migraine Headache Index (MHI) at 6 months |  | 6 months postoperatively | 
| Migraine Headache Index (MHI) at 1 year |  | 1 year postoperatively | 
| Migraine Headache Index (MHI) at 2 years |  | 2 years postoperatively | 
| Migraine Headache Index (MHI) at 2.5 years |  | 2.5 years postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Migraine Disability Assessment Test (MIDAS) score at 1 year |  | 1 year postoperatively | 
| Migraine Disability Assessment Test (MIDAS) score at 2 years |  | 2 years postoperatively | 
| Migraine Disability Assessment Test (MIDAS) score at 2.5 years |  | 2.5 years postoperatively | 
| Migraine Work and Productivity Loss Questionnaire (MMWPLQ) score at 1 year |  | 1 year postoperatively | 
| Migraine Work and Productivity Loss Questionnaire (MMWPLQ) score at 2 years |  | 2 years postoperatively | 
| Migraine Work and Productivity Loss Questionnaire (MMWPLQ) score at 2.5 years |  | 2.5 years postoperatively | 
| Migraine-Specific Quality of Life Questionnaire (MSQ) score at 1 year |  | 1 year postoperatively | 
| Migraine-Specific Quality of Life Questionnaire (MSQ) score at 2 years |  | 2 years postoperatively | 
| Migraine-Specific Quality of Life Questionnaire (MSQ) score at 2.5 years |  | 2.5 years postoperatively | 
| Migraine treatment cost for 2 months |  | For 2 months postoperatively |