NCT02351544

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
44

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Sep 2015

Longer than P75 for not_applicable

Geographic Reach
1 country

6 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 21, 2015

Completed
9 days until next milestone

First Posted

Study publicly available on registry

January 30, 2015

Completed
7 months until next milestone

Study Start

First participant enrolled

September 1, 2015

Completed
6.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2022

Completed
1.9 years until next milestone

Results Posted

Study results publicly available

April 22, 2024

Completed
Last Updated

April 22, 2024

Status Verified

April 1, 2024

Enrollment Period

6.8 years

First QC Date

January 21, 2015

Results QC Date

January 6, 2024

Last Update Submit

April 9, 2024

Conditions

Outcome Measures

Primary Outcomes (3)

  • Migraine Headache Index (MHI) at 1 Year

    MHI is a numerical value calculated by multiplying the severity (1-10 numerical rating scale), duration (fraction of 24 h), and frequency (days per month) of migraine headaches. The lower the value the lower migraine severity reported is. The index range is minimum 0.00 to maximum 300.00.

    1 year postoperatively

  • Migraine Headache Index (MHI) at 2 Years

    MHI is a numerical value calculated by multiplying the severity (1-10 numerical rating scale), duration (fraction of 24 h), and frequency (days per month) of migraine headaches. The lower the value the lower migraine severity reported is. The index range is minimum 0.00 to maximum 300.00.

    2 years postoperatively

  • Migraine Headache Index (MHI) at 2.5 Years

    MHI is a numerical value calculated by multiplying the severity (1-10 numerical rating scale), duration (fraction of 24 h), and frequency (days per month) of migraine headaches. The lower the value the lower migraine severity reported is. The index range is minimum 0.00 to maximum 300.00.

    2.5 years postoperatively

Secondary Outcomes (9)

  • 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

  • +4 more secondary outcomes

Study Arms (2)

Botulinum toxin

EXPERIMENTAL

Patients in this arm will receive botulinum toxin for migraine headaches

Drug: Botulinum Toxin Type AOther: Daily headache diaryOther: Migraine Disability Assessment Test (MIDAS)Other: Migraine Work and Productivity Loss Questionnaire (MWPLQ)Other: Migraine-Specific Quality of Life Questionnaire (MSQ)

Surgery

EXPERIMENTAL

Patients in this arm will receive surgery for migraine headaches

Procedure: SurgeryOther: Daily headache diaryOther: Migraine Disability Assessment Test (MIDAS)Other: Migraine Work and Productivity Loss Questionnaire (MWPLQ)Other: Migraine-Specific Quality of Life Questionnaire (MSQ)

Interventions

Botulinum toxin
SurgeryPROCEDURE
Surgery
Botulinum toxinSurgery

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Peled Plastic Surgery

San Francisco, California, 94118, United States

Location

Premier Plastic Surgery of Kansas City

Olathe, Kansas, 66061, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Neuropax Clinic

St Louis, Missouri, 63161, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

The University of Wisconsin-Madison

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Migraine Disorders

Interventions

Botulinum Toxins, Type ASurgical Procedures, Operative

Condition Hierarchy (Ancestors)

Headache Disorders, PrimaryHeadache DisordersBrain DiseasesCentral Nervous System DiseasesNervous System Diseases

Intervention Hierarchy (Ancestors)

Botulinum ToxinsMetalloendopeptidasesEndopeptidasesPeptide HydrolasesHydrolasesEnzymesEnzymes and CoenzymesMetalloproteasesBacterial ProteinsProteinsAmino Acids, Peptides, and ProteinsBacterial ToxinsToxins, BiologicalBiological Factors

Results Point of Contact

Title
Dr. Jeffrey Janis
Organization
The Ohio State University

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

January 21, 2015

First Posted

January 30, 2015

Study Start

September 1, 2015

Primary Completion

June 1, 2022

Study Completion

June 1, 2022

Last Updated

April 22, 2024

Results First Posted

April 22, 2024

Record last verified: 2024-04

Locations