Study Description

This is a phase III, multi-center, randomized, double-blind, placebo-controlled, prospective, clinical trial examining the outcomes of subjects with chronic migraine headache who are treated with 0.3cc of 0.5% bupivacaine bilaterally vs 0.3cc of sterile water bilaterally, each delivered to the mucosal surface of the SPG through each nare with the Tx360® device.

Subjects must have a current history of ICHD-III beta migraine with > 14 headache days per month (with 8 or more being migraine) in the 3 months prior to the screening visit. Subjects will be required to have a stable history of doses of migraine prophylactic medication for at least 30 days prior to the start of the 28-day screening/baseline phase and for the duration of the study. At Visit 1, the subject will sign the informed consent indicating they are willing to participate in the study. Initially, subjects who meet the study criteria will participate in a 28-day screening/baseline phase. During the 28-day screening/baseline phase, all subjects will be monitored through the use of electronic Daily Headache Diary (DHD) to ensure they continue to meet all inclusion criteria, and none of the exclusion criteria.

If baseline criteria have been met at the end of the 28-day screening/baseline phase, the subject will return to the clinic for Visit 2 to be randomized into one of the two treatment groups and begin the 4-week treatment phase of the study. Subjects who meet all inclusion criteria, and none of the exclusion criteria, will be assigned to a treatment group based on a computerized randomization number produced by a computer software system. One hundred and eighty subjects will be randomized 1:1 to receive 0.3cc of 0.5% bupivacaine bilaterally or 0.3cc of sterile water bilaterally. One member of the staff will allocate study medication, based on the randomization plan, in a blinded fashion to subject, coordinator, and investigator. At Visit 2, the subject will receive the first treatment.

The subject will return to the clinic three times per week for treatments, totaling 12 treatments.

At visit 13, subjects will receive the last treatment and will be transitioned into the post-treatment phase of the study.

The subject will be followed for an additional 3 months during the post-treatment phase for a total of 20 weeks participation in the study. During this post-treatment phase, the subject will maintain the DHD at an 80% participation rate and two monthly phone visits will take place 1 and 2 months post treatment respectively.

The subject will complete the study at Visit 14 to the clinic for final follow-up.

Condition or Disease	Intervention/Treatment
Headache, Migraine	Device: Tx360

Study Design

Study Type	Interventional
Actual Enrollment	174 participants
Design Allocation	Randomized
Interventional Model	Parallel Assignment
Masking	Quadruple
Primary Purpose	Treatment
Official Title	A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel 20 Week Study of the Efficacy and Safety of the Tx360® Nasal Applicator for Transnasal Sphenopalatine Ganglion Block in the Treatment of Chronic Migraine
Study Start Date	September 20, 2017
Actual Primary Completion Date	November 15, 2023
Actual Study Completion Date	December 29, 2023

Groups and Cohorts

Group/ Cohort	Intervention/ Treatment
Bupivacaine Bupivacaine is a local anesthestic that will be delivered to the SPG by the Tx360 device.	Device: Tx360 Tx360 used to deliver active and placebo drug interventions to SPG.
saline Saline is being used as a placebo treatment that will be delivered to the SPG by the Tx360 device.	Device: Tx360 Tx360 used to deliver active and placebo drug interventions to SPG.

Outcome Measures

Primary Outcome Measures

1. Change in Number of Migraine Headaches During Treatment Phase [From 28-day screening/baseline phase to the end of the 4-week treatment phase.]
   Evaluate the efficacy of bupivacaine delivered with the Tx360® device, based on the change in the number of migraine days during treatment.

Secondary Outcome Measures

1. Change in Number of Migraine Headache Days Post-Treatment [From 28-day screening/baseline to end of one month post-treatment, end of two months post-treatment, and end of three months post treatments (EOS)]
   Evaluate the efficacy of bupivacaine delivered with the Tx360® device, based on the change in the number of migraine days post-treatment.
2. Safety/Tolerability of TX360 Device Based on Adverse Effects [Measured per month from end of 28-day screening/baseline phase to end of the 4-week treatment phase, and end of one month post- treatment, end ot two months post-treatment, and end of 3 months post-treatment.(EOS)]
   Evaluate the safety and tolerability of the Tx360® device in the prevention of chronic migraine based on reported adverse effects.

Eligibility Criteria

Ages Eligible for Study	18 Years to 65 Years (Adult, Older Adult)
Sexes Eligible for Study	All
Accepts Healthy Volunteers	No
Inclusion Criteria	Subjects may be included that meet the following criteria: willing to participate and sign informed consent ability to understand informed consent and study procedures, including able to use the electronic Daily Headache Diary in general good health based on investigator's judgment male or female, age must be between 18 to 65 years of age, inclusive chronic migraine meeting the diagnostic criteria listed in the International Classification of Headache Disorders (ICHD-III beta version, 2013), as follows: History of frequent headaches suggestive of chronic migraine (at least 15 days per month with 8 or more being migraine) for at least three months prior to screening Verification of headache frequency through prospectively collected baseline information during the 28-day screening/baseline phase demonstrating headaches at least 15 days, with at least 8 days per month fulfilling any one of the following Qualify as being a migraine Relieved by migraine specific acute medications onset of migraine before age 50 able to differentiate migraine from any other headache they may experience (e.g., tension-type headache) stable history of migraine at least 3 months prior to screening with headache free periods not currently taking a migraine preventive OR has been taking a stable dose of a preventive for at least 60 days prior to screening and agrees to not start, stop, or change medication and/or dosage during the study period a) subjects on migraine preventative should have stable headache pattern subject is either not of childbearing potential, as defined in the methods section, or if they are of childbearing potential they agree either to remain abstinent or use (or have their partner use) an acceptable method of birth control for the duration of the study demonstrated compliance with the electronic Daily Headache Diary during the 28-day screening/baseline phase as defined by entry of headache data on a minimum of 22 to 28 days (80% diary compliance) in or completing the study.
Exclusion Criteria	Subjects will be excluded that meet the following criteria: unable to complete headache records (diary) as required by protocol pregnant, actively trying to become pregnant, or breast-feeding history of medication overuse (MO) of opioids, or butalbital, as defined by ICHD-III beta criteria in the previous 12 months and/or MO during 28-day screening/baseline phase (Appendix B). history of hemiplegic migraine, basilar migraine, cervicogenic headache, occipital neuralgia or post-traumatic headache as defined by ICHD-III beta criteria (Post traumatic headache needs to have developed within 7 days of the following: injury to the head, regaining of consciousness following injury to the head, or discontinuation of medications that impair ability to send or report headache following the injury to the head. has failed greater than 2 migraine preventative medications due to lack of efficacy after adequate trial received onabotulinumtoxinA for migraine or for any medical or cosmetic reasons requiring injections in the head, face, or neck during the 4 months before screening. has a planned military deployment within the 6 months post screening has previously received SPG blocks using the Tx360®device history of substance abuse and/or dependence within the past 5 years, in the judgment of the Investigator unstable neurological condition or a significantly abnormal neurological examination with focal signs or signs of increased intracranial pressure, in the judgment of the investigator suffers from a serious illness, or an unstable medical condition, one that could require hospitalization, or could increase the risk of adverse events, in the judgment of the investigator any psychiatric condition with psychotic features, and/or any other psychiatric disorder not stable or well controlled, that would interfere in the ability to complete study activities malignancy within the past year, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated nasal septal deformity such as cleft lip and palate, choanal atresia, atrophic rhinitis, rhinitis, or septal perforation recent nasal/midface trauma (< 3 months) nasal or facial fracture recent nasal/sinus surgery (< 3 months) bleeding disorder such as Von Willebrand disease or hemophilia severe respiratory distress neoplasm such as Angiofibroma, sinus tumor, granuloma nasal congestion present more than 10 days with fever (temperature ≥ 100.4 F) and nasal mucous is an abnormal color skin around and inside the nasal passage that is dry, cracked, oozing, or bleeding recurrent nose bleeds allergy to bupivacaine has a score > 0 on question 9 of PHQ-9 at any visit received any investigational agents within 30 days prior to Visit 1 plans to participate in another clinical study at any time during this study have any other conditions that in the judgment of the Investigator would make the subject unsuitable for inclusion, or would interfere with the subject participating

Contacts and Locations

Sponsors and Collaborators	Tian Medical Inc., TAMM Net, Inc., Clinvest Research, LLC, Ki Health Partners. LLC
	TAMM Net, Inc., Clinvest Research, LLC, Ki Health Partners. LLC
Locations	Yale University | New Haven, Connecticut, United States, 06519 New England Institute for Clinical Research | Stamford, Connecticut, United States, 06905 Eisenhower Army Medical Center | Fort Gordon, Georgia, United States, 30905 Crescent City Headache and Neurology Centre | Chalmette, Louisiana, United States, 70043 MedVadis Research | Watertown, Massachusetts, United States, 02472 Clinvest Research, LLC | Springfield, Missouri, United States, 65810 Hudson Medical | New York, New York, United States, 10007 North Suffolk Neurology, PC | Port Jefferson Station, New York, United States, 11776 Womack Army Medical Senter | Fort Bragg, North Carolina, United States, 28310 Preferred Primary Care Physicians | Pittsburgh, Pennsylvania, United States, 15236 Lone Star Neurology | Frisco, Texas, United States, 75035
Investigators

More Information

Additional Relevant MeSH Terms

• Migraine Disorders
• Headache
• Headache Disorders, Primary
• Headache Disorders
• Brain Diseases
• Central Nervous System Diseases
• Nervous System Diseases
• Pain
• Neurologic Manifestations