Use of the Tx360 Nasal Applicator in the Treatment of Chronic Migraine (Tx360)

Study Description

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Brief Summary:

Migraine imposes a substantial burden on patients in terms of diminished daily functioning, quality of life, and financial loss. Pain severity and duration correlates with reduced measures of daily functioning, and overall health status. The sphenopalatine ganglion (SPG) has been implicated in a variety of cephalalgias. This has been well represented in the literature dating back over a century. Access to this structure can be gained via a small area of mucosa just posterior and superior to the tail of the middle turbinate on the lateral nasal wall. At this aspect, there is no bony boundary to the SPG. Blocking the SPG using local anesthetics relieves pain. Unfortunately, many current interventions are cumbersome, invasive, and expensive. The purpose of this study is to evaluate the efficacy of the Tx360™, a new nasal applicator device, in the treatment of head and face pain and to examine the economic implications. The Tx360™ is a single use device designed to deliver a topical local anesthetic to the specific area of mucosa associated with the SPG. A total of 42 study participants will be accepted into this double-blind placebo-controlled study. 28 will receive SPG blocks using a 0.3 mL of a 0.5% solution of Marcaine delivered by the Tx360™ while 14 will receive a placebo of saline substituted for the Marcaine. Both patient sets will also be given a piece of lemon hard candy as a taste distractor. Participants must have a chronic migraine history with over 15 symptomatic days per month over the past three months. The treatment plan consists of six weeks of treatment, two times per week. Short and longer term assessments will be retrieved and analyzed as detailed in the Study Design.

Condition or disease	Intervention/treatment	Phase
Chronic Migraine	Drug: Marcaine; Drug: Saline	Phase 4

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Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	41 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
Official Title:	Use of the Tx360 Nasal Applicator for Transnasal Sphenopalatine Ganglion Block in the Treatment of Chronic Migraine: A Double-blind Placebo-controlled Study
Study Start Date :	September 2012
Actual Primary Completion Date :	February 2014
Actual Study Completion Date :	February 2014

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: Marcaine; Group A will receive treatment with 0.3 mL of 0.5% Marcaine delivered bilaterally with the Tx360™ device to the mucosa associated with the Sphenopalatine Ganglion (SPG)	Drug: Marcaine; Marcaine used as a topical local anesthetic to block the SPG by delivering Marcaine directly to the specific area of mucosa associated with the SPG.; Other Name: Bupivicane (generic)
Placebo Comparator: Saline; Group B will receive saline placebo delivered bilaterally with the Tx360TM device to the mucosa associated with the SPG.	Drug: Saline; Saline

Outcome Measures

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Primary Outcome Measures :

1. Numeric Rating Scale (NRS) [ Time Frame: 6 Weeks ]
   Compare Numeric Rating Scale (NRS) scores Before Procedure,15-Minute Post Treatment, 30-Minutes Post Treatment, 24-Hour Post Treatment for all 12 treatments (Marcaine vs. Saline). NRS is a likert scale ranging from 0-10 with 0 being no pain and 10 being worst possible pain. For each individual time point, all 12 treatments were averaged for that time point and a single value was used for comparison between the two groups.

Secondary Outcome Measures :

1. Change in Numeric Rating Scale (NRS) [ Time Frame: 15 Minutes Post Treatment, 30 minutes Post Treatment and 24 hours Post Treatment, assessed up to 6 weeks ]
   Compare percentage change in Numeric Rating Scale (NRS) score from Before Procedure to 15-Minutes, Before Procedure to 30-Minutes, Before Procedure to 24-Hours After Procedure for all 12 treatments (Mean of all 12 treatments for each timepoint, comparing Group A to Group B). NRS is a likert scale ranging from 0-10 with 0 being no pain and 10 being worst possible pain.
2. Patient's Global Impression of Change (PGIC) [ Time Frame: 30 minutes Post Treatment and 24 hours Post Treatment, assessed up to 6 weeks ]
   Compare 24-Hour After Procedure Patient's Global Impression of Change (PGIC) score for 12 treatments (Mean of all 12 treatments for each timepoint, comparing Group A to Group B). PGIC is a likert scale ranging from 1 to 7 with 1 being very much improved and 7 being very much worse.
3. Modified Pain Characteristic Questionnaire [ Time Frame: Before Treatment, 24 Hours After Treatment, 1 Month Post Treatment, and 6 Months Post Treatment ]
   Compare Modified Pain Characteristic Questionnaire scores Before Procedure vs. 24-Hour After Procedure, Before Procedure vs. 1-Month Follow Up, and Before Procedure vs. 6-Month Follow Up (Mean of all 12 treatments for each timepoint, comparing Group A to Group B). The modified pain characteristic questionnaire is a series of 11 questions on a likert scale ranging from 0 to 10 with 0 being no pain or does not interfere and 10 being worst pain or completely interferes. Percentage questions range from 0 to 100.
4. Migraine Headache Days [ Time Frame: 12 Weeks ]
   Compare change in the number of migraine headache days per month reported in Baseline Period Diary vs. Treatment Period Diary vs. Post-Treatment Period Diary.
5. Acute Medications Usage [ Time Frame: 10 Weeks ]
   Number of acute medications used during Treatment period (6 weeks) and Follow-Up (4 weeks) (Group A vs. Group B).
6. Adverse Events [ Time Frame: 34 weeks ]
   Number of adverse events over the entire length of study (Group A vs. Group B).
7. Headache Impact Test (HIT-6) [ Time Frame: 10 Weeks ]
   Total Headache Impact Test (HIT-6) scores Pre-Treatment at Visit 2 vs. Post-Treatment (following final treatment), and at 1-Month Post-Treatment (Group A vs. Group B). HIT-6 is a series of 6 likert scale questions ranging from 1 to 5 with 1 being never and 5 being always. The HIT-6 answer options are weighted as follows: Never (1) = 6 points each, Rarely (2) = 9 points each, Sometimes (3) = 10 points each, Very often (4) = 11 points each, Always (5) = 13 points each. The total score for the HIT-6 ranges from 36 (subject answers all 6 questions as "Never") to 78 subject answers all 6 questions as "Always"), with higher total scores indicating more impact than lower scores, i.e., headaches cause greater impact on the subject's life.
8. Overall Satisfaction [ Time Frame: 10 Weeks ]
   Satisfaction scores Visit 2 vs. following treatment (Treatment 12) and at 1-Month Post-Treatment (Group A vs. Group B). Satisfaction scores are a likert scale ranging from 1 to 5 with 1 being complete dissatisfaction and 5 being complete satisfaction.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 80 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. Is male or female, in otherwise good health, 18 to 80 years of age.
2. Has history of chronic migraine (with or without aura) according to the criteria proposed by the Headache Classification Committee of the International Headache Society for at least 3 months prior to enrollment.
3. Has onset of migraine before age 50.
4. Is able to differentiate migraine from any other headache they may experience (e.g., tension-type headache).
5. Is not currently taking a migraine preventive or has been taking preventive for at least 30 days prior to screening and agrees to not start, stop, or change medication and/or dosage during the study period.

6. If female of childbearing potential, agrees to use, for the duration of the study, a medically acceptable form of contraception as determined by the Investigator.

   1. Complete abstinence from intercourse from 2 weeks prior to administration of study drug throughout the study, and for a time interval after completion or premature discontinuation from the study to account for elimination of the study drug; or,
   2. Surgically sterile (hysterectomy or tubal ligation or otherwise incapable of pregnancy); or,
   3. Sterilization of male partner; or,
   4. Intrauterine device with published data showing lowest expected failure rate is less than 1% per year; or,
   5. Double barrier method (i.e., 2 physical barriers OR 1 physical barrier plus spermicide) for a least 1 month prior to Visit 1 and throughout study; or,
   6. Hormonal contraceptives for at least 3 months prior to Visit 1 and throughout study.
7. Has pain presentation in frontal, temporal, ophthalmic, maxillary, mandibular, facial, or intraoral location.

Exclusion Criteria:

1. Is male or female, in otherwise good health, 18 to 80 years of age.
2. Has history of chronic migraine (with or without aura) according to the criteria proposed by the Headache Classification Committee of the International Headache Society for at least 3 months prior to enrollment.
3. Has onset of migraine before age 50.
4. Is able to differentiate migraine from any other headache they may experience (e.g., tension-type headache).
5. Is not currently taking a migraine preventive or has been taking preventive for at least 30 days prior to screening and agrees to not start, stop, or change medication and/or dosage during the study period.

6. If female of childbearing potential, agrees to use, for the duration of the study, a medically acceptable form of contraception as determined by the Investigator.

   1. Complete abstinence from intercourse from 2 weeks prior to administration of study drug throughout the study, and for a time interval after completion or premature discontinuation from the study to account for elimination of the study drug; or,
   2. Surgically sterile (hysterectomy or tubal ligation or otherwise incapable of pregnancy); or,
   3. Sterilization of male partner; or,
   4. Intrauterine device with published data showing lowest expected failure rate is less than 1% per year; or,
   5. Double barrier method (i.e., 2 physical barriers OR 1 physical barrier plus spermicide) for a least 1 month prior to Visit 1 and throughout study; or,
   6. Hormonal contraceptives for at least 3 months prior to Visit 1 and throughout study.
7. Has pain presentation in frontal, temporal, ophthalmic, maxillary, mandibular, facial, or intraoral location.

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Michigan
Michigan Head Pain & Neurological Institute
Ann Arbor, Michigan, United States, 48104
United States, Missouri
Clinvest/A Division of Banyan Group, Inc.
Springfield, Missouri, United States, 65807

Sponsors and Collaborators

Tian Medical Inc.

Clinvest

Investigators

Principal Investigator:	Tian Xia, MD	Tian Medical Inc.

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Instructions for use and device training 

Publications:

Tepper SJ. A pivotal moment in 50 years of headache history: the first American Migraine Study. Headache. 2008 May;48(5):730-1; discussion 732. doi: 10.1111/j.1526-4610.2008.01117_1.x.

Piagkou M, Demesticha T, Troupis T, Vlasis K, Skandalakis P, Makri A, Mazarakis A, Lappas D, Piagkos G, Johnson EO. The pterygopalatine ganglion and its role in various pain syndromes: from anatomy to clinical practice. Pain Pract. 2012 Jun;12(5):399-412. doi: 10.1111/j.1533-2500.2011.00507.x. Epub 2011 Sep 29. Review. Erratum in: Pain Pract. 2012 Nov;12(8):673.

Oluigbo CO, Makonnen G, Narouze S, Rezai AR. Sphenopalatine ganglion interventions: technical aspects and application. Prog Neurol Surg. 2011;24:171-9. doi: 10.1159/000323049. Epub 2011 Mar 21. Review.

Windsor RE, Jahnke S. Sphenopalatine ganglion blockade: a review and proposed modification of the transnasal technique. Pain Physician. 2004 Apr;7(2):283-6.

Rosenberg M, Phero JC. Regional anesthesia and invasive techniques to manage head and neck pain. Otolaryngol Clin North Am. 2003 Dec;36(6):1201-19. Review.

Wood PB. Role of central dopamine in pain and analgesia. Expert Rev Neurother. 2008 May;8(5):781-97. doi: 10.1586/14737175.8.5.781. Review.

Boivie J. Chapter 48 Central post-stroke pain. Handb Clin Neurol. 2006;81:715-30. doi: 10.1016/S0072-9752(06)80052-7.

Stankewitz A, Voit HL, Bingel U, Peschke C, May A. A new trigemino-nociceptive stimulation model for event-related fMRI. Cephalalgia. 2010 Apr;30(4):475-85. doi: 10.1111/j.1468-2982.2009.01968.x. Epub 2010 Feb 1.

Herrera Tolosana S, Fernández Liesa R, Escolar Castellón Jde D, Pérez Delgado L, Lisbona Alquezar MP, Tejero-Garcés Galve G, Guallar Larpa M, Ortiz García A. [Sphenopalatinum foramen: an anatomical study]. Acta Otorrinolaringol Esp. 2011 Jul-Aug;62(4):274-8. doi: 10.1016/j.otorri.2011.01.009. Epub 2011 Mar 22. Spanish.

Rusu MC. Microanatomy of the neural scaffold of the pterygopalatine fossa in humans: trigeminovascular projections and trigeminal-autonomic plexuses. Folia Morphol (Warsz). 2010 May;69(2):84-91.

Oomen KP, Ebbeling M, de Ru JA, Hordijk GJ, Bleys RL. A previously undescribed branch of the pterygopalatine ganglion. Am J Rhinol Allergy. 2011 Jan-Feb;25(1):50-3. doi: 10.2500/ajra.2011.25.3550.

Siéssere S, Vitti M, Sousa LG, Semprini M, Iyomasa MM, Regalo SC. Anatomic variation of cranial parasympathetic ganglia. Braz Oral Res. 2008 Apr-Jun;22(2):101-5.

Gronseth G, Cruccu G, Alksne J, Argoff C, Brainin M, Burchiel K, Nurmikko T, Zakrzewska JM. Practice parameter: the diagnostic evaluation and treatment of trigeminal neuralgia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the European Federation of Neurological Societies. Neurology. 2008 Oct 7;71(15):1183-90. doi: 10.1212/01.wnl.0000326598.83183.04. Epub 2008 Aug 20. Review.

Yang lY, Oraee S. A novel approach to transnasal sphenopalatine ganglion injection. Pain Physician. 2006 Apr;9(2):131-4.

Kanai A, Suzuki A, Kobayashi M, Hoka S. Intranasal lidocaine 8% spray for second-division trigeminal neuralgia. Br J Anaesth. 2006 Oct;97(4):559-63. Epub 2006 Aug 1.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Cady RK, Saper J, Dexter K, Cady RJ, Manley HR. Long-term efficacy of a double-blind, placebo-controlled, randomized study for repetitive sphenopalatine blockade with bupivacaine vs. saline with the Tx360 device for treatment of chronic migraine. Headache. 2015 Apr;55(4):529-42. doi: 10.1111/head.12546. Epub 2015 Mar 31.

Cady R, Saper J, Dexter K, Manley HR. A double-blind, placebo-controlled study of repetitive transnasal sphenopalatine ganglion blockade with tx360(®) as acute treatment for chronic migraine. Headache. 2015 Jan;55(1):101-16. doi: 10.1111/head.12458. Epub 2014 Oct 23.

Responsible Party:	Tian Medical Inc.
ClinicalTrials.gov Identifier:	NCT01709708 History of Changes
Other Study ID Numbers:	12-004TI
First Posted:	October 18, 2012
Results First Posted:	October 20, 2014
Last Update Posted:	January 26, 2018
Last Verified:	January 2018

Keywords provided by Tian Medical Inc.:

Migraine; Headache; Chronic Migraine; Marcaine; Tx360

Additional relevant MeSH terms:

Migraine Disorders; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Bupivacaine	Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents