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

• ClinicalTrials.gov Identifier: NCT02351544
• Recruitment Status: Completed
• First Posted: January 30, 2015
• Last Update Posted: June 13, 2022
• Sponsor: Ohio State University
• Collaborators: University of Wisconsin, Madison; Massachusetts General Hospital; University Hospitals Cleveland Medical Center
• Information provided by (Responsible Party): Jeffrey E Janis, MD, Ohio State University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Migraine Headaches	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)	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Actual Study Start Date: September 2015
• Actual Primary Completion Date: June 2022
• Actual Study Completion Date: June 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Botulinum toxin; Patients in this arm will receive botulinum toxin for migraine headaches	Drug: Botulinum Toxin Type A; 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)
Experimental: Surgery; Patients in this arm will receive surgery for migraine headaches	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)

Outcome Measures

Primary Outcome Measures :

1. Migraine Headache Index (MHI) at 3 months [ Time Frame: 3 months postoperatively ]
2. Migraine Headache Index (MHI) at 6 months [ Time Frame: 6 months postoperatively ]
3. Migraine Headache Index (MHI) at 1 year [ Time Frame: 1 year postoperatively ]
4. Migraine Headache Index (MHI) at 2 years [ Time Frame: 2 years postoperatively ]
5. Migraine Headache Index (MHI) at 2.5 years [ Time Frame: 2.5 years postoperatively ]

Secondary Outcome Measures :

1. Migraine Disability Assessment Test (MIDAS) score at 1 year [ Time Frame: 1 year postoperatively ]
2. Migraine Disability Assessment Test (MIDAS) score at 2 years [ Time Frame: 2 years postoperatively ]
3. Migraine Disability Assessment Test (MIDAS) score at 2.5 years [ Time Frame: 2.5 years postoperatively ]
4. Migraine Work and Productivity Loss Questionnaire (MMWPLQ) score at 1 year [ Time Frame: 1 year postoperatively ]
5. Migraine Work and Productivity Loss Questionnaire (MMWPLQ) score at 2 years [ Time Frame: 2 years postoperatively ]
6. Migraine Work and Productivity Loss Questionnaire (MMWPLQ) score at 2.5 years [ Time Frame: 2.5 years postoperatively ]
7. Migraine-Specific Quality of Life Questionnaire (MSQ) score at 1 year [ Time Frame: 1 year postoperatively ]
8. Migraine-Specific Quality of Life Questionnaire (MSQ) score at 2 years [ Time Frame: 2 years postoperatively ]
9. Migraine-Specific Quality of Life Questionnaire (MSQ) score at 2.5 years [ Time Frame: 2.5 years postoperatively ]
10. Migraine treatment cost for 2 months [ Time Frame: For 2 months postoperatively ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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)

Contacts and Locations

Locations

United States, California

Peled Plastic Surgery

San Francisco, California, United States, 94118

United States, Kansas

Premier Plastic Surgery of Kansas City

Olathe, Kansas, United States, 66061

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

United States, Missouri

Neuropax Clinic

Saint Louis, Missouri, United States, 63161

United States, Ohio

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States, 43210

United States, Wisconsin

The University of Wisconsin-Madison

Madison, Wisconsin, United States, 53792

Sponsors and Collaborators

Ohio State University

University of Wisconsin, Madison

Massachusetts General Hospital

University Hospitals Cleveland Medical Center

More Information

• Responsible Party: Jeffrey E Janis, MD, Professor, Ohio State University
• ClinicalTrials.gov Identifier: NCT02351544
• Other Study ID Numbers: 2015H0024
• First Posted: January 30, 2015
• Last Update Posted: June 13, 2022
• Last Verified: June 2022

Additional relevant MeSH terms:

Migraine Disorders; Headache; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA; Acetylcholine Release Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Neuromuscular Agents; Peripheral Nervous System Agents