Botulinum Toxin Versus Placebo Injections to Temporalis and Masseter Muscles

NCT03223298 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 1607017383
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 2

Brief Summary

This study aims to determine whether the injection of botulinum toxin A or placebo (unpreserved 0.9% sodium chloride) into the masseter and temporalis muscles provides pain relief and improved jaw function in those who suffer from myofascial pain disorder. The study hypothesis is that botulinum toxin A injection is superior to placebo. The specific research questions are:

1. 1.Is the injection of botulinum toxin A superior to placebo for the improvement in pain?
2. 2.Is the injection of botulinum toxin A superior to placebo for the improvement in function or quality of life (QOL)?
3. 3.Are there any adverse effects that result from injection of botulinum toxin A or placebo into the masseters and temporalis muscles? Limited data exists to support the use of botulinum toxin A in the management of myofascial pain disorder of the masticatory region. Botulinum toxin A is not FDA approved for intra-muscular injection within the masticatory region. Its use in the masticatory region is considered off-label but performed without significant known complications. This study will provide the opportunity to quantitate and qualitate any complications in a large prospective sample of patients.

Conditions

Pain, Head; Pain Syndrome; Temporomandibular Disorder; Myofascial Pain Syndrome; Myofascial Pain

Keywords

Myofascial Pain; Myofascial Pain Disorder; Maxillofacial Pain; Masseter Muscle; Temporalis Muscle; Botulinum Toxin

Outcome Measures

Primary Outcomes (1)

• Change in Jaw Pain as Reported by Patient on Visual Analog Scale (VAS)

  Visual Analog Scale ranging from "no pain (0)" to "pain as bad as it could possibly be (100)"

  Pre-intervention, Change at 1 month post-intervention, Change at 2 months post-intervention, Change at 3 months post-intervention

Secondary Outcomes (3)

• Jaw Function as Measured by Jaw Function Limitation Scale

  Pre-intervention, 1 month post-intervention, 2 months post-intervention, 3 months post-intervention

• Change in Jaw Function as Measured by Maximum Interincisal Opening (MIO)

  Pre-intervention, Change at 1 month post-intervention, Change at 2 months post-intervention, Change at 3 months post-intervention

• Change in Objectively Assessed Quality of Life as Measured by Short Form 36

  Pre-intervention, Change at 1 month post-intervention, Change at 2 months post-intervention, Change at 3 months post-intervention

Study Arms (2)

Botulinum Toxin Type A

EXPERIMENTAL

The intramuscular injections will be performed with the patient awake in the oral and maxillofacial surgery clinic. Three injection sites into bilateral masseter muscles and two injection sites into bilateral temporalis muscles will be identified by having the patient clench. The sites will be marked with a surgical pen prior to injections. The skin at the injection sites will be cleaned with an alcohol swab. Via a 1cc TB syringe and a 30-gauge needle, the subject will then receive 100 units of reconstituted botulinum toxin A. 37.5 units will be injected into each masseter muscle and 12.5 units into each temporalis muscle. A written post-operative instruction sheet will be provided to all patients.

Drug: Botulinum toxin type A

0.9% Sodium Chloride Injection

PLACEBO COMPARATOR

The intramuscular injections will be performed with the patient awake in the oral and maxillofacial surgery clinic. Three injection sites into bilateral masseter muscles and two injection sites into bilateral temporalis muscles will be identified by having the patient clench. The sites will be marked with a surgical pen prior to injections. The skin at the injection sites will be cleaned with an alcohol swab. Via a 1cc TB syringe and a 30-gauge needle, the subject will then receive unpreserved 0.9% sodium chloride. A written post-operative instruction sheet will be provided to all patients.

Drug: 0.9% Sodium Chloride Injection

Interventions

Botulinum toxin type A DRUG

37.5 units injected into each masseter muscle and 12.5 units into each temporalis muscle

Also known as: Botulinum, Botox, Allergan, Botulinum Toxin A

Botulinum Toxin Type A

0.9% Sodium Chloride Injection DRUG

1cc syringe

Also known as: Saline, Placebo

0.9% Sodium Chloride Injection

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age
• Ability to give informed consent
• Myofascial pain of masticatory muscles as defined according to the RDC/TMD criteria
• Baseline pain measured by the subject ≥3.5/10 on visual analog scale

You may not qualify if:

• Baseline pain measured by the subject \<3.5/10 on visual analog scale
• Central/Neuropathic pain disorder affecting the masticatory muscles
• Temporomandibular Joint Arthralgia that is more severe than the myofascial pain disorder affecting the masticatory muscles
• Previous Temporomandibular Joint Surgery
• Systemic arthropathies
• Fibromyalgia
• Allergy to study medications
• Traumatic injury of masticatory muscles or temporomandibular joint within last 12 months
• Mandibular fracture within last 12 months
• Pregnancy or breast feeding
• Cervical radiculopathy or surgery
• Prior botox injection in the masticatory muscles
• Initiation of additional treatment of MPD within the past 3 months

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• New York Presbyterian Hospital: collaborator
• Allergan: collaborator

Study Sites (2)

University of Illinois at Chicago

Chicago, Illinois, 60611, United States

Location

Weill Cornell Medical College - NewYork-Presbyterian Hospital

New York, New York, 10065, United States

Location

Related Publications (7)

• Botulinum Toxin A for Myofascial Pain Syndrome: A Review of the Clinical Effectiveness [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2014 Sep 22. Available from http://www.ncbi.nlm.nih.gov/books/NBK253364/

  PMID: 25392894 BACKGROUND

• Freund B, Schwartz M, Symington JM. Botulinum toxin: new treatment for temporomandibular disorders. Br J Oral Maxillofac Surg. 2000 Oct;38(5):466-71. doi: 10.1054/bjom.1999.0238.

  PMID: 11010775 BACKGROUND

• Freund B, Schwartz M, Symington JM. The use of botulinum toxin for the treatment of temporomandibular disorders: preliminary findings. J Oral Maxillofac Surg. 1999 Aug;57(8):916-20; discussion 920-1. doi: 10.1016/s0278-2391(99)90007-1.

  PMID: 10437718 BACKGROUND

• Guarda-Nardini L, Stecco A, Stecco C, Masiero S, Manfredini D. Myofascial pain of the jaw muscles: comparison of short-term effectiveness of botulinum toxin injections and fascial manipulation technique. Cranio. 2012 Apr;30(2):95-102. doi: 10.1179/crn.2012.014.

  PMID: 22606852 BACKGROUND

• Soares A, Andriolo RB, Atallah AN, da Silva EM. Botulinum toxin for myofascial pain syndromes in adults. Cochrane Database Syst Rev. 2014 Jul 25;2014(7):CD007533. doi: 10.1002/14651858.CD007533.pub3.

  PMID: 25062018 BACKGROUND

• von Lindern JJ, Niederhagen B, Berge S, Appel T. Type A botulinum toxin in the treatment of chronic facial pain associated with masticatory hyperactivity. J Oral Maxillofac Surg. 2003 Jul;61(7):774-8. doi: 10.1016/s0278-2391(03)00153-8.

  PMID: 12856249 BACKGROUND

• Reeve GS, Insel O, Thomas C, Houle AN, Miloro M. Does the Use of Botulinum Toxin in Treatment of Myofascial Pain Disorder of the Masseters and Temporalis Muscles Reduce Pain, Improve Function, or Enhance Quality of Life? J Oral Maxillofac Surg. 2024 Apr;82(4):393-401. doi: 10.1016/j.joms.2023.12.014. Epub 2023 Dec 28.

  PMID: 38228287 DERIVED

MeSH Terms

Conditions

Headache; Somatoform Disorders; Temporomandibular Joint Disorders; Myofascial Pain Syndromes

Interventions

Botulinum Toxins, Type A; Idoxuridine; Sodium Chloride

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Mental Disorders; Craniomandibular Disorders; Mandibular Diseases; Jaw Diseases; Musculoskeletal Diseases; Joint Diseases; Muscular Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors; Deoxyuridine; Uridine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Dr. Gwendolyn S. Reeve
• Organization: Weill Cornell Medicine

gsr9001@med.cornell.edu

(212) 746-5175

Study Officials

• Gwendolyn S Reeve, DMD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

• Michael Miloro, DMD

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Randomization will be carried out by the biostatistics team at Weill Cornell. This will provide assurance that there will be equal patient allocation to both study arms, at each participating site, in the event that the target sample size is not reached. The list will be maintained by the investigational pharmacy. A designated research assistant will be identified at each site to prepare the interventional medication (botulinum versus normal saline). The identity of the agent injected will be unknown to the surgeon as the agent will be drawn up by an assistant in a masked syringe immediately prior to each procedure and labeled with the patient's identifier. Only one assistant at each site will know the identity of the agents during the trial.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Study participants will be randomly allocated to one of two treatment arms (injection of botulinum versus placebo). Blocked randomization will be performed at each of the participating sites. They will be stratified based on study site.

Study Record Dates

• First Submitted: July 11, 2017
• First Posted: July 21, 2017
• Study Start: August 31, 2018
• Primary Completion: March 13, 2020
• Study Completion: March 13, 2020
• Last Updated: February 14, 2023
• Results First Posted: February 14, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)