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

Myofascial Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02230371
• Other study ID #: NC3
• Secondary ID: 2005-006042-41
• Status: Completed
• Phase: Phase 4
• Start date: March 2007
• Est. completion date: December 2014

Study information

• Verified date: March 2021
• Source: Karolinska Institutet
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: December 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Myofascial Pain
• Myofascial Pain Syndromes
• Temporomandibular Disorders
• Temporomandibular Joint Disorders
• Temporomandibular Joint Dysfunction Syndrome

Intervention

Drug:
• Granisetron
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.
• Control (placebo)
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.

Locations

Country	Name	City	State
Sweden	Karolinska Institutet, Department of Dental Medicine	Huddinge

Sponsors (2)

Lead Sponsor	Collaborator
Karolinska Institutet	Folktandvården Stockholms län AB

Country where clinical trial is conducted

Sweden, 

References & Publications (9)

Christidis N, Kopp S, Ernberg M. The effect on mechanical pain threshold over human muscles by oral administration of granisetron and diclofenac-sodium. Pain. 2005 Feb;113(3):265-270. doi: 10.1016/j.pain.2004.10.016. — View Citation

Christidis N, Nilsson A, Kopp S, Ernberg M. Intramuscular injection of granisetron into the masseter muscle increases the pressure pain threshold in healthy participants and patients with localized myalgia. Clin J Pain. 2007 Jul-Aug;23(6):467-72. — View Citation

Ernberg M, Hedenberg-Magnusson B, Alstergren P, Kopp S. The level of serotonin in the superficial masseter muscle in relation to local pain and allodynia. Life Sci. 1999;65(3):313-25. — View Citation

Ernberg M, Lundeberg T, Kopp S. Effect of propranolol and granisetron on experimentally induced pain and allodynia/hyperalgesia by intramuscular injection of serotonin into the human masseter muscle. Pain. 2000 Feb;84(2-3):339-46. — View Citation

Ernberg M, Lundeberg T, Kopp S. Pain and allodynia/hyperalgesia induced by intramuscular injection of serotonin in patients with fibromyalgia and healthy individuals. Pain. 2000 Mar;85(1-2):31-9. — View Citation

Ettlin T. Trigger point injection treatment with the 5-HT3 receptor antagonist tropisetron in patients with late whiplash-associated disorder. First results of a multiple case study. Scand J Rheumatol Suppl. 2004;119:49-50. — View Citation

Färber L, Stratz T, Brückle W, Späth M, Pongratz D, Lautenschläger J, Kötter I, Zöller B, Peter HH, Neeck G, Alten R, Müller W. Efficacy and tolerability of tropisetron in primary fibromyalgia--a highly selective and competitive 5-HT3 receptor antagonist. German Fibromyalgia Study Group. Scand J Rheumatol Suppl. 2000;113:49-54. — View Citation

Müller W, Stratz T. Local treatment of tendinopathies and myofascial pain syndromes with the 5-HT3 receptor antagonist tropisetron. Scand J Rheumatol Suppl. 2004;119:44-8. — View Citation

Späth M, Stratz T, Neeck G, Kötter I, Hammel B, Amberger CC, Haus U, Färber L, Pongratz D, Müller W. Efficacy and tolerability of intravenous tropisetron in the treatment of fibromyalgia. Scand J Rheumatol. 2004;33(4):267-70. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in pressure pain threshold	Assessed with a digital algometer (Somedic Sales, Hörby, Sweden)	8 weeks after treatment
Other	Changes in pressure pain threshold	Assessed with a digital algometer (Somedic Sales, Hörby, Sweden)	6 months after treatment
Primary	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
Primary	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	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
Secondary	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
Secondary	Adverse events	Any possible adverse event is registered	1 week after the first injection
Secondary	Adverse events	Any possible adverse event is registered	1 week after the second injection
Secondary	Adverse events	Any possible adverse event is registered	1 week after the third injection
Secondary	Adverse events	Any possible adverse event is registered	8 weeks after the third injection
Secondary	Adverse events	Any possible adverse event is registered	6 months after the third injection