A Double Blind Study Comparing Hyaluronic Acid, Corticosteroid and Placebo During Arthrocentesis for Temporomandibular Joint (TMJ) Dysfunction

• Sponsor: Emory University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01524913
• Collaborator: University of California, Los Angeles (Other), Oregon Health and Science University (Other), University of Minnesota (Other), University of Cincinnati (Other), University of Pennsylvania (Other)
• Enrollment: 102
• Locations: 5
• Arms: 3
• Duration (Months): 51
• Patients Per Site: 20.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether the administration of hyaluronic acid or corticosteroid during arthrocentesis of the temporomandibular joint provides additional pain relief and improved function.

The overall hypothesis for the study is that hyalgan will result in a 30% reduction in the mean visual analogue scale (VAS) at one month when compared to celestone and placebo.

Condition or Disease	Intervention/Treatment	Phase
Temporomandibular Joint Dysfunction; Pain; Arthrocentesis	Drug: Hyaluronic acid; Drug: Corticosteroid; Drug: Lactated Ringers	Phase 4

Detailed Description

This study will enroll patients with temporomandibular joint dysfunction who are deemed appropriate candidates for irrigation of their jaw joints secondary to pain or limited opening. At the completion of the joint irrigation subjects will be injected by one of three different products to determine if the additional injection results in a further decrease in jaw joint pain and improved opening. Subjects will be followed for 3 months. Those who do not show improvement may be candidates for additional treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 102 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double Blind Randomised Study Comparing Hyaluronic Acid, Corticosteroid and Placebo During Arthrocentesis for Temporomandibular Joint Dysfunction
• Study Start Date: Jan 1, 2012
• Actual Primary Completion Date: Dec 1, 2015
• Actual Study Completion Date: Apr 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Hyaluronic acid	Drug: Hyaluronic acid; 1 cc hyalgan to be injected into superior joint space
Active Comparator: Corticosteroid	Drug: Corticosteroid; 1cc celestone (6 mg/cc) will be injected into the joint space
Placebo Comparator: Saline	Drug: Lactated Ringers; 1 cc lactated ringers solution will be injected into the joint space

Outcome Measures

Primary Outcome Measures

1. Change in Pain Between Baseline and Month 1 Scores [Baseline (preoperation), Month 1]

   The change in pain level was assessed using a single-item visual analogue pain scale at Baseline (preoperatively) and at Month 1. Participants indicate their level on pain on a scale of 0 (no pain) to 10 (worst pain imaginable). The right and left side of each participant's jaw was evaluated separately. The change in pain score was obtained by subtracting the Month 1 score from the Baseline score and a negative value indicates a reduction in pain level.

Secondary Outcome Measures

1. Change in Maximum Incisal Opening (MIO) Between Baseline, Month 1, and Month 3 [Baseline (preoperation), Month 1, Month 3]

   Range of motion was assessed at Baseline (preoperatively) and again at Months 1 and 3 using a millimeter ruler for maximum incisal opening. MIO was measurements were taken for maximum opening without and with pain.

2. Jaw Function Limitation Scale (JFLS) Score [Month 1]

   The Jaw Function Limitation Scale (JFLS) is an 8 item survey where respondents indicate the presence or absence of problems with chewing, drinking, eating hard food, eating soft food, smiling or laughing, yawning, swallowing, and talking. Responses of "no" are scored as "0" and responses of "yes" are scored as "1". The total score categorizes jaw limitation as: none (0), mild (1-3), moderate (4-6), and severe (7-8).

3. Jaw Function Limitation Scale (JFLS) Score [Month 3]

   The Jaw Function Limitation Scale (JFLS) is an 8 item survey where respondents indicate the presence or absence of problems with chewing, drinking, eating hard food, eating soft food, smiling or laughing, yawning, swallowing, and talking. Responses of "no" are scored as "0" and responses of "yes" are scored as "1". The total score categorizes jaw limitation as: none (0), mild (1-3), moderate (4-6), and severe (7-8).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• age greater than 18 years

• arthralgia of one or both temporomandibular joints

• Wilkes II to IV internal derangement of the symptomatic joint OR

• limited opening of <35 mm

Exclusion Criteria:

• myofascial pain as the primary source of pain

• cervical pain as the primary source of pain

• systemic arthropathy

• fibromyalgia

• use of NSAIDS within 48 hours

• allergy to study medications

• edentulous subjects

• pregnancy or breast feeding

• current physical therapy, muscle relaxants or antiseizure medications

• current use of a splint issued within last 12 weeks

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University California Los Angeles	Los Angeles	California	United States	90024
2	Emory University	Atlanta	Georgia	United States	30322
3	University of Cinncinati	Cinncinati	Ohio	United States	45219
4	Oregon Health Sciences University	Portland	Oregon	United States	97239
5	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• Emory University
• University of California, Los Angeles
• Oregon Health and Science University
• University of Minnesota
• University of Cincinnati
• University of Pennsylvania

Investigators

• Principal Investigator: Gary F Bouloux, MD, DDS, Emory University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gary F Bouloux MD, DDS, MDSc, FRACDS, FRACDS, National PI, Emory University
• ClinicalTrials.gov Identifier: NCT01524913
• Other Study ID Numbers: IRB00018682; Arthrocentesis
• First Posted: Feb 2, 2012
• Last Update Posted: May 5, 2017
• Last Verified: Mar 1, 2017

• Additional relevant MeSH terms: Joint Diseases; Temporomandibular Joint Disorders; Temporomandibular Joint Dysfunction Syndrome; Hyaluronic Acid

Study Results

Participant Flow

Recruitment Details	Participants were recruited from patients referred to the oral and maxillary surgery services at Emory University, the University of Pennsylvania, the University of California - Los Angeles, the University of Cincinnati, and the Oregon Health Science University. All patients were referred for management of temporomandibular joint (TMJ) pain.
Pre-assignment Detail	A total of 105 patients were screened; three did not meet inclusion and exclusion criteria, resulting in 102 participants who were randomized and began the study treatment.

Arm/Group Title	Corticosteroid	Hyaluronic Acid	Saline Placebo
Arm/Group Description	Participants in this group received 1 milliliter (mL) of Celestone (6mg/mL) injected into the the superior joint space.	Participants in the group received 1milliliter (mL) of Hyalgan (10 mg/mL) injected into the superior joint space.	Participants in this group received 1 milliliter (mL) of lactated Ringer's solution injected into the superior joint space.
Period Title: Overall Study
STARTED	35	36	31
COMPLETED	31	36	31
NOT COMPLETED	4	0	0

Baseline Characteristics

Arm/Group Title	Corticosteroid	Hyaluronic Acid	Saline Placebo	Total
Arm/Group Description	Participants in this group received 1mL of Celestone (6mg/mL) injected into the the superior joint space.	Participants in the group received 1mL of Hyalgan (10 mg/mL) injected into the superior joint space.	Participants in this group received 1mL of lactated Ringer's solution injected into the superior joint space.	Total of all reporting groups
Overall Participants	35	36	31	102
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.6 (18.4)	44.3 (17.2)	51.8 (17.2)	45.0 (18.1)
Sex: Female, Male (Count of Participants)
Female	31 88.6%	30 83.3%	28 90.3%	89 87.3%
Male	4 11.4%	6 16.7%	3 9.7%	13 12.7%
Race/Ethnicity, Customized (Count of Participants)
African American	6 17.1%	7 19.4%	6 19.4%	19 18.6%
White	25 71.4%	28 77.8%	23 74.2%	76 74.5%
Asian	1 2.9%	0 0%	1 3.2%	2 2%
Other	3 8.6%	1 2.8%	1 3.2%	5 4.9%
Region of Enrollment (participants) [Number]
United States	35 100%	36 100%	31 100%	102 100%
Headache (Count of Participants)
Yes	19 54.3%	17 47.2%	16 51.6%	52 51%
No	16 45.7%	19 52.8%	15 48.4%	50 49%
Migraine (Count of Participants)
Yes	12 34.3%	9 25%	7 22.6%	28 27.5%
No	23 65.7%	27 75%	24 77.4%	74 72.5%
Prior TMJ Surgery (Count of Participants)
Yes	5 14.3%	4 11.1%	1 3.2%	10 9.8%
No	30 85.7%	32 88.9%	30 96.8%	92 90.2%
Capsular Pain (Count of Participants)
Yes	26 74.3%	28 77.8%	24 77.4%	78 76.5%
No	9 25.7%	8 22.2%	7 22.6%	24 23.5%
Myofascial Pain (Count of Participants)
Yes	15 42.9%	24 66.7%	20 64.5%	59 57.8%
No	20 57.1%	12 33.3%	11 35.5%	43 42.2%
Cervical Pain (Count of Participants)
Yes	11 31.4%	13 36.1%	9 29%	33 32.4%
No	24 68.6%	23 63.9%	22 71%	69 67.6%
Clicking Jaw (Count of Participants)
Yes	14 40%	14 38.9%	9 29%	37 36.3%
No	21 60%	22 61.1%	22 71%	65 63.7%
Crepitus (Count of Participants)
Yes	5 14.3%	6 16.7%	2 6.5%	13 12.7%
No	30 85.7%	30 83.3%	29 93.5%	89 87.3%

Outcome Measures

1. Primary Outcome

Title	Change in Pain Between Baseline and Month 1 Scores
Description	The change in pain level was assessed using a single-item visual analogue pain scale at Baseline (preoperatively) and at Month 1. Participants indicate their level on pain on a scale of 0 (no pain) to 10 (worst pain imaginable). The right and left side of each participant's jaw was evaluated separately. The change in pain score was obtained by subtracting the Month 1 score from the Baseline score and a negative value indicates a reduction in pain level.
Time Frame	Baseline (preoperation), Month 1

Outcome Measure Data

Analysis Population Description

The population at this time point consists of study participants who received their assigned intervention and were not lost to follow up by the Month 1 assessment.

Arm/Group Title	Corticosteroid	Hyaluronic Acid	Saline Placebo
Arm/Group Description	Participants in this group received 1mL of Celestone (6mg/mL) injected into the the superior joint space.	Participants in the group received 1mL of Hyalgan (10 mg/mL) injected into the superior joint space.	Participants in this group received 1mL of lactated Ringer's solution injected into the superior joint space.
Measure Participants	31	36	31
Change in Pain - Right Side	-1.1 (2.8)	-1.7 (3.0)	-2.6 (2.8)
Change in Pain - Left Side	-2.0 (3.1)	-2.1 (3.1)	-2.3 (3.2)

2. Secondary Outcome

Title	Change in Maximum Incisal Opening (MIO) Between Baseline, Month 1, and Month 3
Description	Range of motion was assessed at Baseline (preoperatively) and again at Months 1 and 3 using a millimeter ruler for maximum incisal opening. MIO was measurements were taken for maximum opening without and with pain.
Time Frame	Baseline (preoperation), Month 1, Month 3

Outcome Measure Data

Analysis Population Description

The population for MIO analysis consists of participants having a measurement at each specified time point. The decline in the number of participants over time is due to participants who were lost to follow-up as the study progressed and one participant who attended the Month 3 visit but did not provide data for the MIO assessment.

Arm/Group Title	Corticosteroid	Hyaluronic Acid	Saline Placebo
Arm/Group Description	Participants in this group received 1mL of Celestone (6mg/mL) injected into the the superior joint space.	Participants in the group received 1mL of Hyalgan (10 mg/mL) injected into the superior joint space.	Participants in this group received 1mL of lactated Ringer's solution injected into the superior joint space.
Measure Participants	35	36	31
Baseline MIO without pain	28.3 (8.4)	27.9 (11.2)	25.7 (7.5)
Baseline MIO maximum	37.0 (8.5)	33.9 (10.3)	34.1 (7.8)
Month 1 MIO without pain	35.0 (9.4)	31.7 (11.4)	29.6 (10.6)
Month 1 MIO maximum	39.0 (10.5)	36.8 (11.2)	37.4 (6.7)
Month 3 MIO without pain	36.1 (11.3)	33.9 (11.7)	35.7 (5.0)
Month 3 MIO maximum	37.8 (15.0)	38.3 (13.2)	39.3 (5.3)

3. Secondary Outcome

Title	Jaw Function Limitation Scale (JFLS) Score
Description	The Jaw Function Limitation Scale (JFLS) is an 8 item survey where respondents indicate the presence or absence of problems with chewing, drinking, eating hard food, eating soft food, smiling or laughing, yawning, swallowing, and talking. Responses of "no" are scored as "0" and responses of "yes" are scored as "1". The total score categorizes jaw limitation as: none (0), mild (1-3), moderate (4-6), and severe (7-8).
Time Frame	Month 1

Outcome Measure Data

Analysis Population Description

The population at this time point consists of study participants who received the intervention they were randomized to and were not lost to follow-up before the Month 1 visit.

Arm/Group Title	Corticosteroid	Hyaluronic Acid	Saline Placebo
Arm/Group Description	Participants in this group received 1mL of Celestone (6mg/mL) injected into the the superior joint space.	Participants in the group received 1mL of Hyalgan (10 mg/mL) injected into the superior joint space.	Participants in this group received 1mL of lactated Ringer's solution injected into the superior joint space.
Measure Participants	31	36	31
None	3 8.6%	5 13.9%	6 19.4%
Mild	18 51.4%	14 38.9%	14 45.2%
Moderate	9 25.7%	14 38.9%	9 29%
Severe	1 2.9%	3 8.3%	2 6.5%

4. Secondary Outcome

Title	Jaw Function Limitation Scale (JFLS) Score
Description	The Jaw Function Limitation Scale (JFLS) is an 8 item survey where respondents indicate the presence or absence of problems with chewing, drinking, eating hard food, eating soft food, smiling or laughing, yawning, swallowing, and talking. Responses of "no" are scored as "0" and responses of "yes" are scored as "1". The total score categorizes jaw limitation as: none (0), mild (1-3), moderate (4-6), and severe (7-8).
Time Frame	Month 3

Outcome Measure Data

Analysis Population Description

The population at this time point consists of study participants who received the intervention they were randomized to, were not lost to follow-up before the Month 3 visit, and completed assessments at the Month 3 visit (one participant did not provide JFLS data at the Month 3 time point).

Arm/Group Title	Corticosteroid	Hyaluronic Acid	Saline Placebo
Arm/Group Description	Participants in this group received 1mL of Celestone (6mg/mL) injected into the the superior joint space.	Participants in the group received 1mL of Hyalgan (10 mg/mL) injected into the superior joint space.	Participants in this group received 1mL of lactated Ringer's solution injected into the superior joint space.
Measure Participants	19	17	15
None	5 14.3%	5 13.9%	6 19.4%
Mild	8 22.9%	7 19.4%	5 16.1%
Moderate	5 14.3%	4 11.1%	4 12.9%
Severe	1 2.9%	1 2.8%	0 0%

Adverse Events

Time Frame	Adverse events were assessed up to three months after arthrocentesis. Allergic reactions were watched for during the procedure and during the 30 minute recovery period after the procedure. Post injection flare was monitored after 1 month. All other adverse events were monitored during for three months post-procedure.
Adverse Event Reporting Description	Adverse events were actively sought, including allergic reactions (anaphylaxis, angioedema, urticaria), post-injection flare, hospital admission, the need for additional procedures to prevent or limit permanent injury, and death and other life threatening events. Given the extensive safe track record of hyaluronic acid and the corticosteroid Celestone, no adverse events were expected to occur.
Arm/Group Title	Corticosteroid		Hyaluronic Acid		Saline Placebo
Arm/Group Description	Participants in this group received 1mL of Celestone (6mg/mL) injected into the the superior joint space.		Participants in the group received 1mL of Hyalgan (10 mg/mL) injected into the superior joint space.		Participants in this group received 1mL of lactated Ringer's solution injected into the superior joint space.
All Cause Mortality
	Corticosteroid		Hyaluronic Acid		Saline Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Corticosteroid		Hyaluronic Acid		Saline Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		0/36 (0%)		0/31 (0%)
Other (Not Including Serious) Adverse Events
	Corticosteroid		Hyaluronic Acid		Saline Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		0/36 (0%)		0/31 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.