Study on the Effect of Granisetron on Myofascial Pain in the Orofacial Muscles

Study Overview
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Brief Summary
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The aim of this study is to to investigate if local treatment with intramuscular injections of granisetron are effective in alleviating pain in patients with chronic myofascial pain in the orofacial muscles The study hypothesis is that local administration of granisetron reduces pain and allodynia/hyperalgesia in patients with chronic myofascial pain in the orofacial muscles and that this effect of granisetron on pain is larger than the effect from placebo

Detailed Description
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This randomized, placebo-controlled, double blind trial (RCT) is carried out during the period of May 2006 to December 2014 as a multicenter study. The two participating centers are the Section of Orofacial Pain and Jaw Function, Department of Dental Medicine, Karolinska Institutet, Sweden and Department of Clinical Oral Physiology at the Eastman Institute, Folktandvården Stockholms län AB, Stockholm, Sweden. The patients are divided randomly into two groups that receive either granisetron or placebo. The randomization is performed by computer (www.randomization.com) by a research assistant not participating in data collection. The study comprise seven visits; V1) Screening for study participation, V2) First treatment, V3) Second treatment, V4) Third treatment, and V5 to V7) Follow-ups at 1, 2 and 12 months (Fig. Y1) V1 (baseline) include a general health questionnaire, the RDC/TMD Axis II questionnaires (25), the McGill Pain Questionnaire (MPQ) (27), pain drawings of the lateral side of the head (each side separately), and a 1-week pain diary. In addition, a clinical examination according to the RDC/TMD Axis I is performed, including registration of the maximum voluntary mouth opening capacity (MUMO), and also registration of the pressure pain threshold (PPT) as well as blood sampling. V2-V4 include a shortened clinical examination according to RDC including registration of MUMO and PPT, treatment with intramuscular injections of study substance and a 1-week pain diary. At V3 and V4 a patient's global assessment of treatment outcome questionnaire is also included. V5-V7 include the RDC/TMD Axis II questionnaires, the McGill Pain Questionnaire (MPQ), pain drawings of the lateral side of the head (each side separately), a 1-week pain diary, a patient's global assessment of treatment outcome questionnaire, a clinical examination according to the RDC/TMD Axis I including registration of MUMO and PPT, and registration of adverse events. Three orofacial pain specialists (N.C., L.F., B.H.M.) and one dentist attending a specialist training program (S.O.) will be calibrated in the RDC/TMD examination technique to a gold standard examiner (M.E.) during one day, and will perform the study. They and the patients are blinded to group assignment (i.e. study substance) during the entire trial and the substances used will not be revealed until the last patient has undergone the last follow-up.

Official Title
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The Serotonin Receptor Type 3 Antagonist Granisetron as a New Treatment Approach for Patients With Chronic Myofascial Pain in the Orofacial Muscles

Conditions
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Myofascial Pain, Temporomandibular Disorders

Intervention / Treatment
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* Drug: Granisetron
* Drug: Control (placebo)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age ≥ 18 years a diagnosis of myofascial pain according to the research diagnostic criteria for TMD Axis I (RDC/TMD) duration of TMD pain ≥ 3 months self-assessed average myofascial-TMD pain intensity of ≥ 30 mm on a 100-mm visual analogue scale (VAS) during one week prior to examination familiar pain upon digital palpation of the masseter and/or the temporalis muscles. The patients remain included with one or several co-diagnoses of; a) disc displacement with or without reduction, b) osteoarthrosis in the any of the temporomandibular joints (TMJ), and c) episodic or chronic tension type headache Exclusion Criteria: diagnosed systemic muscular or joint diseases (e.g. fibromyalgia, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis) whiplash associated disorder neuropathic pain or neurological disorders (e.g. myasthenia gravis, orofacial dystonia) history of psychiatric disorders pain of dental origin use of muscle relaxants or any medication that might influence the response to pain pregnancy or lactation known hypersensitivity to granisetron

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Granisetron<br>Granisetron (Kytril®; 1 mg/mL, Roche, Stockholm, Sweden) is injected into a maximum of six muscle sites in each patient. The most painful sites to palpation of the masticatory muscles is chosen, either in the same muscle (maximum 3 sites per muscle) or in a different. The injected volume into each site is0.5 mL, hence the maximum dose of granisetron a patient can receive is 3 mg per treatment. This is repeated after one and two weeks. | Drug: Granisetron<br>* If the patient does not have any pain after the first or second injection of granisetron (Kytril®; 1 mg/mL, Roche, Stockholm, Sweden), there will be no more injections but the patient will still come for the follow ups.<br>* Other names: Kytril (Roche);|
| Placebo Comparator: Control (placebo)<br>Placebo (isotonic saline (NaCl); 0.9 mg/mL, Fresenius Kabi, Uppsala, Sweden) is injected into a maximum of six muscle sites in each patient. The most painful sites to palpation of the masticatory muscles is chosen, either in the same muscle (maximum 3 sites per muscle) or in a different. The injected volume into each site is 0.5 mL. This is repeated after one and two weeks. | Drug: Control (placebo)<br>* If the patient does not have any pain after the first or second injection of granisetron (isotonic saline (NaCl); 0.9 mg/mL, Fresenius Kabi, Uppsala, Sweden), there will be no more injections but the patient will still come for the follow ups.<br>* Other names: Isotonic saline 9%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensity | Change of the median weekly pain intensity compared to baseline A 100-mm VAS is used for each day of the week | 8 weeks after treatment | 
| Pain intensity | Change of the median weekly pain intensity compared to baseline A 100-mm VAS is used for each day of the week | 6 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical and emotional functioning | Assessed with Axis II of the RDC/TMD (research diagnostic criteria for temporomandibular disorders), including the questionnaires: Graded Chronic Pain Scale SCL-90R | 8 weeks after treatment | 
| Physical and emotional functioning | Assessed with Axis II of the RDC/TMD (research diagnostic criteria for temporomandibular disorders), including the questionnaires: Graded Chronic Pain Scale SCL-90R | 6 months after treatment | 
| Adverse events | Any possible adverse event is registered | 1 week after the first injection | 
| Adverse events | Any possible adverse event is registered | 1 week after the second injection | 
| Adverse events | Any possible adverse event is registered | 1 week after the third injection | 
| Adverse events | Any possible adverse event is registered | 8 weeks after the third injection | 
| Adverse events | Any possible adverse event is registered | 6 months after the third injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myofascial pain, TMD, 5-HT3, Granisetron, Placebo-controlled, Patients, Randomized, Double-blind