Comparison of Psychological and Pharmacological Treatments for Pain Due to Temporomandibular Joint Disorder (TMD)

• Sponsor: Johns Hopkins University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00066937
• Collaborator: National Institute of Dental and Craniofacial Research (NIDCR) (NIH)
• Enrollment: 140
• Location: 1
• Arms: 4
• Duration (Months): 68
• Patients Per Site Per Month: 2.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether the combination of cognitive-behavioral treatment and nortriptyline are more effective than each treatment alone in reducing the pain and disability associated with TMD.

Condition or Disease	Intervention/Treatment	Phase
Temporomandibular Joint Disorders	Drug: Nortriptyline Oral Capsule; Drug: Benztropine Oral Product; Behavioral: CBT; Behavioral: Disease MGT	Phase 2

Detailed Description

This is a randomized, controlled trial evaluating pharmacological (nortriptyline vs. active placebo - benztropine) and psychological (cognitive-behavioral therapy vs. disease education) treatments for pain and disability due to temporomandibular joint disorder (TMD). Patients 18 to 65 years old meeting RDC criteria for TMD and other eligibility criteria complete a 3-week baseline monitoring phase prior to randomization. Active treatment consists of weekly visits for 8 week, then maintenance treatment for 6 months. Outcome measures include pain, physical and psychosocial function and are assessed at post-treatment, 3-months, and 6-months

Study Design

• Study Type: Interventional
• Actual Enrollment: 140 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Pain Management in Temporomandibular Joint Disorders
• Study Start Date: Nov 1, 2002
• Actual Primary Completion Date: Jun 1, 2008
• Actual Study Completion Date: Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nortriptyline Oral Capsule/CBT Nortriptyline taken at bedtime titrated to a dose up to 150 mg. Study participants also receive 6 sessions of CBT.	Drug: Nortriptyline Oral Capsule; Nortriptyline will be titrated up from 25 mg qhs to a maximum dose of 150 mg qhs based on treatment response and side effect profile.; Behavioral: CBT; Six in-person, individual sessions of cognitive-behavioral therapy for pain management include relaxation training, pain coping skills training, cognitive therapy for negative and dysfunctional thoughts, and diaries for monitoring relaxation, goals, and negative thinking.
Experimental: Benztropine Oral Product/CBT Benztropine will be titrated up from .125 mg qhs to a maximum dose of .750 mg qhs based on treatment response and side effect profile. Study participants also receive 6 sessions of CBT.	Drug: Benztropine Oral Product; Benztropine will be titrated up from .125 mg qhs to a maximum dose of .750 mg qhs based on treatment response and side effect profile.; Behavioral: CBT; Six in-person, individual sessions of cognitive-behavioral therapy for pain management include relaxation training, pain coping skills training, cognitive therapy for negative and dysfunctional thoughts, and diaries for monitoring relaxation, goals, and negative thinking.
Experimental: Nortriptyline Oral Capsule/Disease MGT Nortriptyline taken at bedtime titrated to a dose up to 150 mg. Study participants also receive 6 sessions of TMD disease management.	Drug: Nortriptyline Oral Capsule; Nortriptyline will be titrated up from 25 mg qhs to a maximum dose of 150 mg qhs based on treatment response and side effect profile.; Behavioral: Disease MGT; Six in-person, individual sessions of temporomandibular joint disorder (TMD) disease management (MGT) that include information about the jaw and good oral habits, diet, sleep, and general stress management.
Active Comparator: Benztropine Oral Product/Disease MGT Benztropine will be titrated up from .125 mg qhs to a maximum dose of .750 mg qhs based on treatment response and side effect profile. Study participants also receive 6 sessions of TMD disease management.	Drug: Benztropine Oral Product; Benztropine will be titrated up from .125 mg qhs to a maximum dose of .750 mg qhs based on treatment response and side effect profile.; Behavioral: Disease MGT; Six in-person, individual sessions of temporomandibular joint disorder (TMD) disease management (MGT) that include information about the jaw and good oral habits, diet, sleep, and general stress management.

Outcome Measures

Primary Outcome Measures

1. Average Pain [baseline, post-treatment, 3 months, 6 months]

   0 (no pain) to 10 (pain as bad as could be) rating of average pain during the past week; higher scores indicate greater pain

2. Change in Pain-related Interference [baseline, post-treatment, 3 months, 6 months]

   Multidimensional Pain Inventory: Pain interference subscale score; average score computed from 12 items rated on scale from 0=no interference to 6=extreme interference; higher scores indicate greater pain-related interference

Secondary Outcome Measures

1. Worst Pain [baseline, post-treatment, 3 months, 6 months]

   0 (no pain) to 10 (pain as bad as could be) rating of worst pain during the past week

2. Mental Health as Assessed by the Short Form 36 Healthy Survey [baseline, post-treatment, 3 months, 6 months]

   The Mental Health Component score from the Short Form (36) Health Survey, which is a 36-item, patient-reported survey of patient health. The mental health component score is calculated from responses to the general health, mental health, vitality, physical and emotional role limitations, and social functioning subscales, with higher scores indicating better mental health. The scale ranges from zero (equivalent to maximum disability) to 100 (no disability).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion:

• Age >= 18 and <= 65

• Pain >= 3 months duration due to temporomandibular joint disorder

• Pain due to TMD is primary if other pain conditions present

Exclusion:

• Continuous, chronic painful non-reducing disc displacement of TMJ and patient can't open mouth

• Unstable or acute severe pain from another pain condition

• Patient is pregnant

• Presence of a medical condition that contraindicates nortriptyline: angle-closure glaucoma,symptomatic orthosis

• EKG: first degree heart block or QTc > 450 msec

• Unstable angina or a history of a myocardial infarction within the past 3 months

• Current treatment with an antidepressant which cannot be withdrawn

• Current use of a medication that interacts with nortriptyline to raise blood levels, such as selective serotonin reuptake inhibitors (e.g.,paroxetine), systemic anti-fungal agents (fluconazole), antiarrhythmics (e.g., quinidine), antipsychotics (e.g., haloperidol), and antibiotics (e.g., erythromycin).

• Presence of dementia, psychosis or other disorder of cognition that impairs ability to participate in minimal contact intervention

• Beck Depression Inventory (BDI) score >= 35 OR BDI Item #9 (suicide item) is scored > 1

• Patient has a terminal illness with a life expectancy of less than six months

• History of arthrotomy of temporomandibular joint

• History of allergic reaction to nortriptyline or benztropine

• History of a therapeutic trial with nortriptyline (dose >= 100 mg for at least 3 weeks)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Maryland, Dental School	Baltimore	Maryland	United States	21201

Sponsors and Collaborators

• Johns Hopkins University
• National Institute of Dental and Craniofacial Research (NIDCR)

Investigators

• Principal Investigator: Jennifer A Haythornthwaite, Ph.D, Johns Hopkins University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT00066937
• Other Study ID Numbers: RPN 00-03-21-02; R01DE013906
• First Posted: Aug 8, 2003
• Last Update Posted: Jul 24, 2017
• Last Verified: Jul 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Joint Diseases; Temporomandibular Joint Disorders; Temporomandibular Joint Dysfunction Syndrome; Benztropine; Nortriptyline

Study Results

Participant Flow

Arm/Group Title	Nortriptyline Oral Capsule/CBT	Benztropine Oral Product/CBT	Nortriptyline Oral Capsule/Disease MGT	Benztropine Oral Product/Disease MGT
Arm/Group Description	Nortriptyline taken at bedtime titrated to a dose up to 150 mg. Study participants also receive 6 sessions of CBT.	Benztropine will be titrated up from .125 mg qhs to a maximum dose of .750 mg qhs based on treatment response and side effect profile. Study participants also receive 6 sessions of CBT.	Nortriptyline taken at bedtime titrated to a dose up to 150 mg. Study participants also receive 6 sessions of TMD disease management.	Benztropine will be titrated up from .125 mg qhs to a maximum dose of .750 mg qhs based on treatment response and side effect profile. Study participants also receive 6 sessions of TMD disease management.
Period Title: Treatment Phase
STARTED	41	38	37	24
COMPLETED	38	33	26	19
NOT COMPLETED	3	5	11	5
Period Title: Treatment Phase
STARTED	38	33	26	19
COMPLETED	33	32	25	15
NOT COMPLETED	5	1	1	4
Period Title: Treatment Phase
STARTED	33	32	25	15
COMPLETED	26	29	22	14
NOT COMPLETED	7	3	3	1

Baseline Characteristics

Arm/Group Title	Nortriptyline Oral Capsule/CBT	Benztropine Oral Product/CBT	Nortriptyline Oral Capsule/Disease MGT	Benztropine Oral Product/Disease MGT	Total
Arm/Group Description	Nortriptyline taken at bedtime titrated to a dose up to 150 mg. Study participants also receive 6 sessions of CBT.	Benztropine will be titrated up from .125 mg qhs to a maximum dose of .750 mg qhs based on treatment response and side effect profile. Study participants also receive 6 sessions of CBT.	Nortriptyline taken at bedtime titrated to a dose up to 150 mg. Study participants also receive 6 sessions of TMD disease management.	Benztropine will be titrated up from .125 mg qhs to a maximum dose of .750 mg qhs based on treatment response and side effect profile. Study participants also receive 6 sessions of TMD disease management.	Total of all reporting groups
Overall Participants	41	38	37	24	140
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.7 (12.0)	38.4 (12.5)	37.2 (11.5)	33.3 (11.3)	36.4 (11.9)
Sex: Female, Male (Count of Participants)
Female	31 75.6%	29 76.3%	28 75.7%	17 70.8%	105 75%
Male	10 24.4%	9 23.7%	9 24.3%	7 29.2%	35 25%
Region of Enrollment (participants) [Number]
United States	41 100%	38 100%	37 100%	24 100%	140 100%

Outcome Measures

1. Primary Outcome

Title	Average Pain
Description	0 (no pain) to 10 (pain as bad as could be) rating of average pain during the past week; higher scores indicate greater pain
Time Frame	baseline, post-treatment, 3 months, 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nortriptyline Oral Capsule/CBT	Benztropine Oral Product/CBT	Nortriptyline Oral Capsule/Disease MGT	Benztropine Oral Product/Disease MGT
Arm/Group Description	Nortriptyline taken at bedtime titrated to a dose up to 150 mg. Study participants also receive 6 sessions of CBT.	Benztropine will be titrated up from .125 mg qhs to a maximum dose of .750 mg qhs based on treatment response and side effect profile. Study participants also receive 6 sessions of CBT.	Nortriptyline taken at bedtime titrated to a dose up to 150 mg. Study participants also receive 6 sessions of TMD disease management.	Benztropine will be titrated up from .125 mg qhs to a maximum dose of .750 mg qhs based on treatment response and side effect profile. Study participants also receive 6 sessions of TMD disease management.
Measure Participants	38	33	26	19
baseline	4.7 (2.2)	4.4 (2.1)	4.5 (2.2)	5.0 (1.8)
post treatment	2.8 (2.6)	2.7 (2.1)	2.0 (1.4)	2.8 (2.1)
3 months	2.1 (1.6)	2.4 (2.2)	2.2 (2.1)	2.5 (2.1)
6 months	2.0 (1.7)	2.0 (2.1)	1.4 (1.6)	2.2 (2.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nortriptyline Oral Capsule/CBT, Benztropine Oral Product/CBT, Nortriptyline Oral Capsule/Disease MGT, Benztropine Oral Product/Disease MGT
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<.05
	Comments
	Method	ANOVA
	Comments	Repeated measures ANOVAs compared baseline to each timepoint

2. Primary Outcome

Title	Change in Pain-related Interference
Description	Multidimensional Pain Inventory: Pain interference subscale score; average score computed from 12 items rated on scale from 0=no interference to 6=extreme interference; higher scores indicate greater pain-related interference
Time Frame	baseline, post-treatment, 3 months, 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nortriptyline Oral Capsule/CBT	Benztropine Oral Product/CBT	Nortriptyline Oral Capsule/Disease MGT	Benztropine Oral Product/Disease MGT
Arm/Group Description	Nortriptyline taken at bedtime titrated to a dose up to 150 mg. Study participants also receive 6 sessions of CBT.	Benztropine will be titrated up from .125 mg qhs to a maximum dose of .750 mg qhs based on treatment response and side effect profile. Study participants also receive 6 sessions of CBT.	Nortriptyline taken at bedtime titrated to a dose up to 150 mg. Study participants also receive 6 sessions of TMD disease management.	Benztropine will be titrated up from .125 mg qhs to a maximum dose of .750 mg qhs based on treatment response and side effect profile. Study participants also receive 6 sessions of TMD disease management.
Measure Participants	38	33	26	19
Change in score from baseline to post-treatment	0.9 (0.9)	0.5 (0.9)	0.5 (0.7)	1.0 (0.9)
Change in score from baseline to 3 months	0.8 (0.9)	0.8 (0.9)	1.0 (0.9)	1.1 (1.2)
Change in score from baseline to 6 months	0.8 (0.8)	0.7 (1.2)	0.7 (0.8)	0.8 (1.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nortriptyline Oral Capsule/CBT, Benztropine Oral Product/CBT, Nortriptyline Oral Capsule/Disease MGT, Benztropine Oral Product/Disease MGT
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<.05
	Comments
	Method	ANOVA
	Comments	Repeated measures ANOVAs compared baseline scores to each period of follow-up (post-treatment, 3-months, 6 months)

3. Secondary Outcome

Title	Worst Pain
Description	0 (no pain) to 10 (pain as bad as could be) rating of worst pain during the past week
Time Frame	baseline, post-treatment, 3 months, 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nortriptyline Oral Capsule/CBT	Benztropine Oral Product/CBT	Nortriptyline Oral Capsule/Disease MGT	Benztropine Oral Product/Disease MGT
Arm/Group Description	Nortriptyline taken at bedtime titrated to a dose up to 150 mg. Study participants also receive 6 sessions of CBT.	Benztropine will be titrated up from .125 mg qhs to a maximum dose of .750 mg qhs based on treatment response and side effect profile. Study participants also receive 6 sessions of CBT.	Nortriptyline taken at bedtime titrated to a dose up to 150 mg. Study participants also receive 6 sessions of TMD disease management.	Benztropine will be titrated up from .125 mg qhs to a maximum dose of .750 mg qhs based on treatment response and side effect profile. Study participants also receive 6 sessions of TMD disease management.
Measure Participants	38	33	26	19
baseline	6.7 (2.3)	6.1 (2.2)	6.3 (2.4)	7.2 (1.9)
post-treatment	4.0 (2.9)	4.1 (2.8)	3.2 (2.1)	4.4 (2.6)
3 months	3.6 (2.4)	3.3 (2.3)	3.4 (2.7)	4.1 (2.9)
6 months	3.3 (2.1)	3.1 (2.7)	2.7 (2.2)	3.4 (2.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nortriptyline Oral Capsule/CBT, Benztropine Oral Product/CBT, Nortriptyline Oral Capsule/Disease MGT, Benztropine Oral Product/Disease MGT
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<.05
	Comments
	Method	ANOVA
	Comments	Repeated measures ANOVAs compared baseline scores to each period of follow-up (post-treatment, 3-months, 6 months)

4. Secondary Outcome

Title	Mental Health as Assessed by the Short Form 36 Healthy Survey
Description	The Mental Health Component score from the Short Form (36) Health Survey, which is a 36-item, patient-reported survey of patient health. The mental health component score is calculated from responses to the general health, mental health, vitality, physical and emotional role limitations, and social functioning subscales, with higher scores indicating better mental health. The scale ranges from zero (equivalent to maximum disability) to 100 (no disability).
Time Frame	baseline, post-treatment, 3 months, 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nortriptyline Oral Capsule/CBT	Benztropine Oral Product/CBT	Nortriptyline Oral Capsule/Disease MGT	Benztropine Oral Product/Disease MGT
Arm/Group Description	Nortriptyline taken at bedtime titrated to a dose up to 150 mg. Study participants also receive 6 sessions of CBT.	Benztropine will be titrated up from .125 mg qhs to a maximum dose of .750 mg qhs based on treatment response and side effect profile. Study participants also receive 6 sessions of CBT.	Nortriptyline taken at bedtime titrated to a dose up to 150 mg. Study participants also receive 6 sessions of TMD disease management.	Benztropine will be titrated up from .125 mg qhs to a maximum dose of .750 mg qhs based on treatment response and side effect profile. Study participants also receive 6 sessions of TMD disease management.
Measure Participants	38	33	26	19
baseline	50.5 (8.1)	49.2 (9.3)	51.2 (8.8)	48.0 (8.9)
post-treatment	50.8 (10.4)	48.4 (8.1)	52.6 (10.0)	53.3 (10.6)
3 months	51.5 (8.9)	50.2 (8.7)	52.6 (10.0)	53.8 (10.1)
6 months	52.2 (7.8)	53.3 (12.8)	52.3 (7.2)	53.6 (7.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nortriptyline Oral Capsule/CBT, Benztropine Oral Product/CBT, Nortriptyline Oral Capsule/Disease MGT, Benztropine Oral Product/Disease MGT
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<.05
	Comments
	Method	ANOVA
	Comments	Repeated measures ANOVAs compared baseline scores to each period of follow-up (post-treatment, 3-months, 6 months)

Adverse Events

Time Frame	Adverse event data were collected weekly during the treatment phase, then at 3- and 6-months
Arm/Group Title	Nortriptyline Oral Capsule/CBT		Benztropine Oral Product/CBT		Nortriptyline Oral Capsule/Disease MGT		Benztropine Oral Product/Disease MGT
Arm/Group Description	Nortriptyline taken at bedtime titrated to a dose up to 150 mg. Study participants also receive 6 sessions of CBT.		Benztropine will be titrated up from .125 mg qhs to a maximum dose of .750 mg qhs based on treatment response and side effect profile. Study participants also receive 6 sessions of CBT.		Nortriptyline taken at bedtime titrated to a dose up to 150 mg. Study participants also receive 6 sessions of TMD disease management.		Benztropine will be titrated up from .125 mg qhs to a maximum dose of .750 mg qhs based on treatment response and side effect profile. Study participants also receive 6 sessions of TMD disease management.
All Cause Mortality
	Nortriptyline Oral Capsule/CBT		Benztropine Oral Product/CBT		Nortriptyline Oral Capsule/Disease MGT		Benztropine Oral Product/Disease MGT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0%)		0/38 (0%)		0/37 (0%)		0/24 (0%)
Serious Adverse Events
	Nortriptyline Oral Capsule/CBT		Benztropine Oral Product/CBT		Nortriptyline Oral Capsule/Disease MGT		Benztropine Oral Product/Disease MGT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0%)		0/38 (0%)		0/37 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	Nortriptyline Oral Capsule/CBT		Benztropine Oral Product/CBT		Nortriptyline Oral Capsule/Disease MGT		Benztropine Oral Product/Disease MGT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/41 (78%)		24/38 (63.2%)		21/37 (56.8%)		15/24 (62.5%)
Gastrointestinal disorders
constipation	10/41 (24.4%)		7/38 (18.4%)		9/37 (24.3%)		4/24 (16.7%)
General disorders
drymouth	20/41 (48.8%)		14/38 (36.8%)		13/37 (35.1%)		9/24 (37.5%)
Nervous system disorders
sedation	7/41 (17.1%)		8/38 (21.1%)		7/37 (18.9%)		3/24 (12.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.