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

NCT ID: NCT02230371

Last Updated: 2021-03-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-03-31

Study Completion Date

2014-12-31

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.

Conditions

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Myofascial Pain Temporomandibular Disorders

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Granisetron

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.

Group Type EXPERIMENTAL

Granisetron

Intervention Type DRUG

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)

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.

Group Type PLACEBO_COMPARATOR

Control (placebo)

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type DRUG

Other Intervention Names

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Kytril (Roche) Isotonic saline 9%

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Folktandvården Stockholms län AB

OTHER_GOV

Sponsor Role collaborator

Karolinska Institutet

OTHER

Sponsor Role lead

Responsible Party

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Nikolaos Christidis

Assistant professor, PhD, DDS, Senior Consultant

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Nikolaos Christidis, PhD, DDS

Role: PRINCIPAL_INVESTIGATOR

Karolinska Institutet, Department of Dental Medicine

Locations

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Karolinska Institutet, Department of Dental Medicine

Huddinge, , Sweden

Site Status

Countries

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Sweden

References

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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.

Reference Type BACKGROUND
PMID: 15661432 (View on PubMed)

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. doi: 10.1097/AJP.0b013e318058abb1.

Reference Type BACKGROUND
PMID: 17575485 (View on PubMed)

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. doi: 10.1016/s0304-3959(99)00221-3.

Reference Type BACKGROUND
PMID: 10666539 (View on PubMed)

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. doi: 10.1016/s0304-3959(99)00233-x.

Reference Type BACKGROUND
PMID: 10692600 (View on PubMed)

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. doi: 10.1016/s0024-3205(99)00250-7.

Reference Type BACKGROUND
PMID: 10447217 (View on PubMed)

Farber L, Stratz T, Bruckle W, Spath M, Pongratz D, Lautenschlager J, Kotter I, Zoller B, Peter HH, Neeck G, Alten R, Muller 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. doi: 10.1080/030097400446643.

Reference Type BACKGROUND
PMID: 11028832 (View on PubMed)

Spath M, Stratz T, Neeck G, Kotter I, Hammel B, Amberger CC, Haus U, Farber L, Pongratz D, Muller W. Efficacy and tolerability of intravenous tropisetron in the treatment of fibromyalgia. Scand J Rheumatol. 2004;33(4):267-70. doi: 10.1080/03009740410005818.

Reference Type BACKGROUND
PMID: 15370724 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15515414 (View on PubMed)

Muller 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.

Reference Type BACKGROUND
PMID: 15515413 (View on PubMed)

Christidis N, Omrani S, Fredriksson L, Gjelset M, Louca S, Hedenberg-Magnusson B, Ernberg M. Repeated tender point injections of granisetron alleviate chronic myofascial pain--a randomized, controlled, double-blinded trial. J Headache Pain. 2015;16:104. doi: 10.1186/s10194-015-0588-3. Epub 2015 Dec 3.

Reference Type DERIVED
PMID: 26634569 (View on PubMed)

Other Identifiers

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2005-006042-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NC3

Identifier Type: -

Identifier Source: org_study_id

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