Clinical trial NCT03346252: The Effect of Botulinum Toxin A on Headache Attributed to TMD
Official title: The Effect of Botulinum Toxin A (BOTOX®) on Headache Attributed to TMD - An Open Label Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Secondary Headache Disorder
Lead sponsor: State University of New York at Buffalo
Sponsor class: OTHER
First posted: 2017-11-17
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open Label.
Primary purpose: TREATMENT

Brief summary: This study will evaluate the effect of of botulinum toxin on the treatment of Headache Attributed to TMD.

Detailed description: Temporomandibular Disorders (TMD) is a collective term, embracing a number of clinical problems that involve the masticatory muscles, the temporomandibular joint (TMJ) and the associated structures. The prime manifestation consists of pain of a persistent, recurring, or chronic nature . Pain-related TMD can affect the individual's daily activities, psychosocial functioning, and quality of life . The prevalence of TMD is about 10 % in the general population, making it the second most common musculoskeletal condition, after chronic lower back pain, that results in pain and disability . It has been estimated that the annual TMD management cost in the USA, excluding diagnostic imaging, in the last decade was approximately $4 billion.

The pathophysiology of pain-related TMD is poorly understood. However, multiple risk factors have been identified, such as, gender, pain during jaw function and palpation, oral parafunctions, other pain conditions, pain sensitivity and psychosocial characteristics. Because of its multifactorial nature, a multimodal conservative treatment approach is recommended, including patient education, behavioral management, physical therapy, pharmacotherapy, and occlusal splints.

Among the pain-related TMD conditions are "Headaches Attributed to TMD". This diagnosis has replaced "Headaches or facial pain attributed to Temporomandibular Joint (TMJ) disorder" described in the International Classification of Headache Disorders II (ICHD-2). It is characterized by pain in the temple area secondary to pain-related TMD that is modified by function and parafunction affected by jaw movement, function, or parafunction.

In general, headache treatment is either abortive or prophylactic. Abortive treatment manages acute headache and prophylactic treatment aims to reduce the frequency and severity of the attacks. Intramuscular injections with Botulinum Toxin (BTX) are used in the prophylactic treatment of migraine and tension type headaches. The mechanisms by which the analgesic effects of BTX are mediated are not fully understood. One mechanism is the inhibition of neurogenic inflammation by blocking neurotransmitter release from sensitized nociceptors, thus reducing peripheral sensitization. In vitro, BTX has been found to inhibit Calcitonin Gene-Related Peptide (CGRP), and BTX reduces the vascular response to algogenic substances such as capsaicin applied to human skin. Other potential analgesic mechanisms include retrograde transport of BTX by sensory neurons and inhibition of neurotransmitter release by their central terminals.

In recent years, BTX has also been used in the treatment of myogenous-TMD with mixed results. Two randomized controlled trials (RCTs) showed therapeutic benefits of BTX in the management of myogenous -TMD, while another 3 RCTs reported no significant effect of BTX in chronic myogenous -TMD pain. Varying patient samples, methodologies, and sample sizes may explain the differences. Additionally, the results have been compromised by poor methodologies, such as insufficiently powered clinical trials, and open-labeled studies. More recently, a systematic review of randomized controlled trials concluded that no consensus could be reached on the therapeutic benefit of BTX on TMD. More so, no trial on the effectiveness of BTX on the prophylactic treatment of headaches attributed to TMD has been reported to date.

The purpose of this study is to determine the effectiveness of Botulinum toxin - A in the management of headaches attributed to TMD.

Study Design The study will be carried out in the clinics of TMD and Orofacial Pain, School of Dental Medicine, University at Buffalo. A prospective open label design will be used to assess the effectiveness of BTX in the management of Headaches Attributed to TMD.

Recruitment will be done through advertising throughout the clinic and the community.

Eligibility criteria: Inclusion Criteria:

* Adults age 18 to 74 years old.
* Participants with Headaches Attributed to TMD based on Diagnostic Criteria for TMD (DC-TMD) criteria.
* A minimum of 15 headaches/events per month, for the last 3 months.
* Average pain intensity in the last month of ≥5 (0 to 10 scale) where 0 is no pain and 10 is the worst pain ever.

Exclusion Criteria:

* Pregnancy
* Participants with a history of neurological/neuromuscular disorders and bleeding disorders.
* Participants taking prescribed analgesics, muscle relaxants, amino glycosides, or anticholinesterases.
* Participants currently under BTX treatment.
* Participants currently under active treatment for TMD during the last month, which includes physical therapy and pharmacological management.

Primary outcomes:
measure: Reduction in number of Headaches Attributed to TMD (HA)
timeFrame: Every 12 weeks up to 1 year
measure: Reduction in Headache Impact Test-6 score (HIT-6)
timeFrame: Every 12 weeks up to 1 year
measure: Pressure Pain Threshold
timeFrame: Every 12 weeks up to 1 year
Secondary outcomes:
measure: Graded Chronic Pain Scale (GCPS), 1 and 6 months score
timeFrame: Every 12 weeks up to 1 year
measure: Jaw Functional Limitation Scale
timeFrame: Every 12 weeks up to 1 year
measure: Migraine Disability Assessment/ HA-TMD
timeFrame: Every 12 weeks up to 1 year
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: University at Buffalo
state: New York
Study officials:
affiliation: University at Buffalo
name: Yoly M Gonzalez-Stucker, DDS, MS, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schiffman E, Ohrbach R, Truelove E, Look J, Anderson G, Goulet JP, List T, Svensson P, Gonzalez Y, Lobbezoo F, Michelotti A, Brooks SL, Ceusters W, Drangsholt M, Ettlin D, Gaul C, Goldberg LJ, Haythornthwaite JA, Hollender L, Jensen R, John MT, De Laat A, de Leeuw R, Maixner W, van der Meulen M, Murray GM, Nixdorf DR, Palla S, Petersson A, Pionchon P, Smith B, Visscher CM, Zakrzewska J, Dworkin SF; International RDC/TMD Consortium Network, International association for Dental Research; Orofacial Pain Special Interest Group, International Association for the Study of Pain. Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) for Clinical and Research Applications: recommendations of the International RDC/TMD Consortium Network* and Orofacial Pain Special Interest Groupdagger. J Oral Facial Pain Headache. 2014 Winter;28(1):6-27. doi: 10.11607/jop.1151.