Secondary Headache DisorderEarly Phase 1NCT03346252
The Effect of Botulinum Toxin A on Headache Attributed to TMD
A Early Phase 1 study testing Botulinum Toxin type A in people with Secondary Headache Disorder, run by State University of New York at Buffalo at 1 site in United States.
Trial summary
This study will evaluate the effect of of botulinum toxin on the treatment of Headache Attributed to TMD. Read more about this study
- Who is it for?
- Ages 18 to 74 years, women only
- Conditions the study is for
- Secondary Headache Disorder
- What is being tested?
- Botulinum Toxin type A
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 8 May 2017to 15 Mar 2021
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 74 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Botulinum Toxin A (BOTOX®) on Headache Attributed to TMD - An Open Label Trial
This study will evaluate the effect of of botulinum toxin on the treatment of Headache Attributed to TMD.
Read the 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.
- Conditions
- Secondary Headache Disorder
- Being tested
- Botulinum Toxin type A
- Medical subject headings
- Headache Disorders, Secondary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called Botox
All the participants meeting the inclusion criteria will be seen for a total of 4 visits and 3 phone interviews. Participants will complete a set of self-reporting questionnaires, assessing the disability associated with Headaches Attributed to TMD, and other pain-related TMD diagnoses, the impact of headaches on the quality of life, and psychosocial distress questionnaires.
In addition, they will undergo 3 cycles of treatment, each 12 weeks apart.
| Study group | Role | What they receive |
|---|---|---|
| Botulinum Toxin type A | Experimental | Participants will be injected intramuscularly with total of 50 Units, 25 units of Botulinum A per temporalis muscle. The BTX injection will be prepared by dissolving 100 U vial in 2 ml of 0.9 % of Sodium Chloride (NaCl), yielding 25 U/ml. Each participant will receive 0.1 ml of BTX/NaCl mixture in 5 spots per temporalis muscle. Receives: Drug: Botulinum Toxin type A |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction in number of Headaches Attributed to TMD (HA)
Self-report
Measured: Every 12 weeks up to 1 year
Reduction in Headache Impact Test-6 score (HIT-6)
Self-report.
Measured: Every 12 weeks up to 1 year
Pressure Pain Threshold
Using algometer at the temporalis and masseter muscles
Measured: Every 12 weeks up to 1 year
Secondary outcomes (3)
Graded Chronic Pain Scale (GCPS), 1 and 6 months score
This scale provides the characterization of chronic pain as well as disability associated to the chronic pain. This scale includes 3 items for pain intensity and 4 items for function, one item for number of days of pain.
Characteristic Pain Intensity (CPI): compute mean of items 2-4(pain right now, worst pain, average pain), and multiply by 10.
Interference Score: compute mean of items 6-8 (daily activities, social activities, work activities), and multiply by 10.
Interpretation Determination of Chronic Pain Grade Grade 0: (no pain, no disability)
I Low intensity pain, without disability: (Less than 50 points in CPI and less than 3 point in disability)
II: High Intensity pain, without disability: (Greater than or equal to 50 points in CPI and less than 3 point in disability
III: Moderately limiting: N/A in CPI and 3-4 points in disability
IV: Severely limiting: N/A in CPI and 5-6 points in disability
Measured: Every 12 weeks up to 1 year
Jaw Functional Limitation Scale
Comprised within a 20-item instrument. a single global score of "jaw functional limitation" can be computed as the mean of the available items. Sub-scale scores for each type of functional limitation are computed, as follows: Mastication: mean of items 1-6. Mobility: mean of items 7-10. Verbal and non-verbal communication: mean of items 13-20. Norms have not yet been established for this instrument.
Measured: Every 12 weeks up to 1 year
Migraine Disability Assessment/ HA-TMD
This self reported instruments comprise 6 items and based on the number of days of disability a MIDAS level is calculated as follows:
0 to 5- MIDAS Grade I, Little or no disability 6 to 10- MIDAS Grade II, Mild disability 11 to 20- MIDAS Grade III, Moderate disability 21+ MIDAS Grade IV, Severe disability
Measured: Every 12 weeks up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2017
- Study start8 May 2017
- Primary completion15 Mar 2021
- Study completion15 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Secondary Headache DisorderStudies of the same condition, open and under way.
- More trials run by State University of New York at BuffaloThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open Label.
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- State University of New York at Buffalo
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yoly M. Gonzalez-Stucker, State University of New York at Buffalo
- Investigators
- Yoly M Gonzalez-Stucker, DDS, MS, MPH, Principal investigator, University at Buffalo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03346252
- Sponsor's protocol ID
- STUDY00000054
- Status last verified
- Sep 2022
- First submitted
- 31 Jul 2017
- Last updated
- 4 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 24482784
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Botulinum Toxin A (BOTOX®) on Headache Attributed to TMD - An Open Label Trial
- ClinicalTrials.gov ID
- NCT03346252
- Acronym / sponsor ID
- STUDY00000054
- Conditions
- Secondary Headache Disorder
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- State University of New York at BuffaloUniversity, hospital or other
- Study start
- 8 May 2017 (actual)
- Primary completion
- 15 Mar 2021 (actual)
- Study completion
- 15 Mar 2021 (actual)
- First posted
- 17 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open Label.
| Arm | Type | Receives |
|---|---|---|
| Botulinum Toxin type A | Experimental | Drug: Botulinum Toxin type AParticipants will be injected intramuscularly with total of 50 Units, 25 units of Botulinum A per temporalis muscle. The BTX injection will be prepared by dissolving 100 U vial in 2 ml of 0.9 % of Sodium Chloride (NaCl), yielding 25 U/ml. Each participant will receive 0.1 ml of BTX/NaCl mixture in 5 spots per temporalis muscle. |
Who may qualify
- Ages
- 18 to 74 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Botulinum Toxin type AAlso: BotoxAll the participants meeting the inclusion criteria will be seen for a total of 4 visits and 3 phone interviews. Participants will complete a set of self-reporting questionnaires, assessing the disability associated with Headaches Attributed to TMD, and other pain-related TMD diagnoses, the impact of headaches on the quality of life, and psychosocial distress questionnaires. In addition, they will undergo 3 cycles of treatment, each 12 weeks apart. | Drug | Botulinum Toxin type A |
Primary outcome
Reduction in number of Headaches Attributed to TMD (HA)
Time frame: Every 12 weeks up to 1 year
Self-report
Reduction in Headache Impact Test-6 score (HIT-6)
Time frame: Every 12 weeks up to 1 year
Self-report.
Pressure Pain Threshold
Time frame: Every 12 weeks up to 1 year
Using algometer at the temporalis and masseter muscles
3 secondary outcomes
Graded Chronic Pain Scale (GCPS), 1 and 6 months score
Time frame: Every 12 weeks up to 1 year
Jaw Functional Limitation Scale
Time frame: Every 12 weeks up to 1 year
Migraine Disability Assessment/ HA-TMD
Time frame: Every 12 weeks up to 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2022.
- Background: PubMed 24482784Schiffman 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yoly M Gonzalez-Stucker, DDS, MS, MPH principal investigator
University at Buffalo
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Botulinum Toxin type A in people with Secondary Headache Disorder, run by State University of New York at Buffalo at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reduction in number of Headaches Attributed to TMD (HA) (time frame: Every 12 weeks up to 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03346252, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2022.