Biobehavioral Pain Management in TMD

NCT01794624 | Completed DMC

• 2 other identifiers: NA_00070364R01DE019731
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 2

Brief Summary

TMD is a poorly understood chronic pain disorder that affects up to 15% of the adult population, notably impacting women, is linked to greater healthcare utilization, and associated with multiple pain-related co-morbidities. Pain-related catastrophizing (CAT) and sleep continuity disturbance (SCD) are well established modifiable risk factors for TMD and other idiopathic pain conditions. Neither the causal status nor the neurobiological mechanisms by which these factors exert their effects on clinical pain have been established. We propose that CAT and SCD influence clinical pain through shared alterations in pain modulation and key neurobiological pathways, including amplified inflammatory activity, autonomic activity, and adrenocortical functioning. Beyond these shared mechanisms, however, we propose to determine whether pre-sleep CAT increases cortical arousal during sleep. The cognitive dimensions of pre-sleep arousal, particularly rumination and negative sleep-related thoughts, are central to the phenomenology of insomnia. Extending this notion, we propose that CAT in those experiencing ongoing clinical pain fosters sleep disturbance owing to increased pre- and peri-sleep cognitive arousal. Moreover, we propose that pre-sleep CAT is related to subtle variations in objective indices of fragmented sleep (e.g., cortical arousal). We will examine key hypotheses derived from this framework using a brief, prospective randomized experiment, which will permit careful analysis of the temporal patterning of how changes in either CAT or SCD influence each other and contribute to alterations in pain modulatory systems, key nociceptive mechanisms, and clinical pain. Women experiencing at least moderate chronic TMD pain (N=225) who demonstrate at least mild trait catastrophizing and meet at least subclinical insomnia criteria (SCD) will be randomly assigned to: 1) cognitive therapy for catastrophizing (CT-CAT); 2) behavior therapy for sleep disturbance (BT-SCD); or 3) TMD education (Control). Assessments of clinical pain, sleep disturbance, catastrophizing, pain sensitivity and modulatory systems, and indices of inflammatory activity, adrenocortical function and autonomic balance will be completed at baseline, 4 weeks (mid-manipulation) and 8 weeks (post-manipulation). Clinical pain, sleep, catastrophizing and covariates will additionally be measured at 16 weeks (follow-up).

Conditions

Temporomandibular Joint Disorder

Keywords

TMD; TMJD; Temporomandibular Joint Disorders; Sleep Continuity Disturbance; Pain Catastrophizing; Cognitive Therapy; Behavioral Therapy

Outcome Measures

Primary Outcomes (1)

• To investigate a proposed causal chain for TMJD pain based on changes in pain modulation, inflammatory profile and clinical pain.

  Two interventions that experimentally manipulate TMJD pain risk factors (behavioral therapy focusing on sleep continuity disturbance \[BT-SCD\] and cognitive therapy focusing on pain-related catastrophizing \[CT-CAT\]) will be compared with a control (education about TMJD and its treatments), to assess changes in and temporal relationships of pain modulation, pain-evoked inflammatory activity and clinical pain. PAIN MODULATION: Mid change (Visit 6 to Visit 8) in temporal summation and Conditioned Pain Modulation (CPM) INFLAMMATORY PROFILE: Mid change (Visit 6 to Visit 8) in plasma levels of Interleukin-6(IL-6) in blood samples obtained before, during and after Quantitative Sensory Testing (QST) CLINICAL PAIN: Late change (Visit 8 to 3 month follow-up) in the Brief Pain Inventory (BPI) rating of pain severity

  Pain modulation and Inflammatory profile: Visit 6-8; Clinical Pain: Visit 8 to 3 month follow up

Secondary Outcomes (3)

• Impact of pre-sleep cognitive arousal on autonomic and cortical arousal during sleep

  at end of 5 year long study

• Determine if manipulation of TMJD pain risk factors (SCD and CAT) reduces autonomic/cortical arousal.

  at Visit 8 per participant (day 63 +/- 1 week)

• Determine if BT-SCD and CT-CAT treatments alter clinical pain and inflammatory activity relative to control.

  at Visit 6 (Day 35 +/- 2 weeks) to Visit 8 (Day 63 +/- 2 weeks) per participant

Study Arms (3)

Cognitive Therapy

ACTIVE COMPARATOR

Cognitive Therapy for Catastrophizing

Behavioral: Cognitive Therapy for Catastrophizing

Behavioral Therapy

ACTIVE COMPARATOR

Behavioral Therapy for Sleep Continuity Disturbance

Behavioral: Behavioral Therapy for Sleep Continuity Disturbance

TMJD Education

NO INTERVENTION

6-sessions of TMJD disease education/support control

Interventions

Cognitive Therapy for Catastrophizing BEHAVIORAL

Cognitive Therapy for Catastrophizing will involve a standardized, 6-session cognitive intervention, focusing on cognitive restructuring techniques for managing pain and reducing catastrophic thinking and includes some general coping skills training. Cognitive restructuring includes identifying patterns of dysfunctional thinking which can give rise to emotional distress, physiological arousal, or maladaptive behaviors. Patients are taught to identify and replace distorted thinking with balanced, realistic thinking. Patients learn to identify these thoughts as they occur in daily life and challenge their own negative thoughts.

Also known as: CT-CAT, CT, CAT

Cognitive Therapy

Behavioral Therapy for Sleep Continuity Disturbance BEHAVIORAL

Behavioral Therapy for Sleep Continuity Disturbance (BT-SCD) will involve 6-sessions of standardized interventions on sleep restriction therapy (SRT), stimulus control therapy (SCT), and sleep hygiene education. Sleep Restriction curtails the amount of time in bed so that it matches the average baseline amount of total sleep time. Stimulus Control Therapy re-establishes the bed and bedroom as cues for sleep by insuring the patient does not spend significant time in bed awake and/or engaging in sleep-incompatible behaviors. Sleep Hygiene Education uses motivational interviewing to teach subjects about environmental and behavioral factors which may influence sleep. SRT and SCT alone or combined have demonstrated overwhelming efficacy and effectiveness.

Also known as: BT-SCD, SCD, BT

Behavioral Therapy

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Provides a signed and dated informed consent form
• Is a female between 18 and 60 years of age
• Meets Research Diagnostic Criteria/ Temporomandibular Joint Disorders (RDC-TJMD)Axis I TMJD diagnosis at Visit 1
• Reports facial pain present for \> 3 months
• Reports facial pain present on \> 10 days of the last 30 days
• At Visit 1 (Screening visit), reports an average pain severity score over the past week of ≥3 on a numerical rating scale (0-10)
• Reports trouble initiating and/or maintaining sleep regularly (\> 3 days/week) for at least 1 month
• Scores \> 8 on the Insomnia Severity Scale at Visit 2
• Scores \> 8 on the Pain Catastrophizing Scale at Visit 2
• If using non-opioid medication for pain treatment:
• Has been on the same treatment regimen for the last 30 days prior to Visit 1
• Is willing to stay on the same treatment regimen for the duration of the study, with the addition of rescue medications (as needed use of opioid \< 3x/week, non-steroidal anti-inflammatory, acetaminophen, or aspirin). Use of rescue medications is restricted to use only more than 24 hours prior to QST.
• If using an opioid for pain treatment or a benzodiazepine/benzodiazepine receptor agonist or sedating tricyclic antidepressant (e.g., trazodone, amitriptyline, doxepin) for sleep \> 3 days/week, is willing to undergo a 4-week washout period prior to enrolling in the study.
• If of child-bearing potential, agrees at Visit 2 to use contraception throughout the study.
• If post-menopausal, has been so for at least 12 consecutive months prior to Visit 1

You may not qualify if:

• BMI \> 35 at Visit 2
• Resting systolic blood pressure \> 140 mm Hg and diastolic blood pressure \> 90 mm Hg at Visit 2
• History of any type of TMJ surgery or TMJ growth disturbances, neoplasm, or injury to the TMJ area within the past six months
• Scheduled for surgery for TMJ during study participation period.
• History of major medical disease known to impact sleep, the central nervous system (e.g., chronic obstructive pulmonary disease, seizure disorder, systemic lupus erythematosus, multiple sclerosis, cancer, congestive heart failure), or peripheral neuropathy.
• Diagnosis of Raynaud's Syndrome
• History of unstable major psychiatric disorder
• Active \[within 6 months\] substance or alcohol abuse
• Regular (≥ 3x/week) use of opioids, benzodiazepines/benzodiazepine receptor agonists, or sedating tricyclic antidepressants reported at Visit 1
• Stable preferred sleep phase between 10am and 10pm (i.e., night workers) or self-reported variability in sleep due to changes in work shift (i.e., nurses or emergency workers)
• Score ≥ 27 on Center for Epidemiologic Studies of Depression Scale (CES-D) or self-reported suicidal ideation
• Positive urine toxicology screening test (barbiturates, marijuana, alcohol, cocaine and other recreational drugs of abuse) at Visit 2
• Positive urine pregnancy test at Visit 2
• Respiratory Disturbance Index (RDI) \> 15 as determined from the Baseline PSG
• Periodic limb movement index with arousals \> 15 as determined from the Baseline PSG

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institute of Dental and Craniofacial Research (NIDCR): collaborator
• University of Maryland: collaborator

Study Sites (2)

University of Maryland Dental School: Brotman Facial Pain Clinic

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins Bayview Meidical Center: Behavioral Medicine Research Laboratory

Baltimore, Maryland, 21224, United States

Location

Related Publications (2)

• Mun CJ, Tsang S, Reid MJ, Tennen H, Haythornthwaite JA, Finan PH, Smith MT. Effects of sleep and circadian rest-activity rhythms on daily pain severity in women with temporomandibular disorders. Pain. 2025 Mar 28;166(7):1487-1496. doi: 10.1097/j.pain.0000000000003578.

  PMID: 40198735 DERIVED

• Lerman SF, Mun CJ, Hunt CA, Kunatharaju S, Buenaver LF, Finan PH, Campbell CM, Phillips J, Fernandez-Mendoza J, Haythornthwaite JA, Smith MT. Insomnia with objective short sleep duration in women with temporomandibular joint disorder: quantitative sensory testing, inflammation and clinical pain profiles. Sleep Med. 2022 Feb;90:26-35. doi: 10.1016/j.sleep.2022.01.004. Epub 2022 Jan 8.

  PMID: 35091170 DERIVED

MeSH Terms

Conditions

Temporomandibular Joint Disorders

Interventions

Cognitive Behavioral Therapy; Tomography Scanners, X-Ray Computed; Behavior Therapy

Condition Hierarchy (Ancestors)

Craniomandibular Disorders; Mandibular Diseases; Jaw Diseases; Musculoskeletal Diseases; Joint Diseases; Muscular Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Psychotherapy; Behavioral Disciplines and Activities; Equipment and Supplies

Study Officials

• Jennifer A Haythornthwaite

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Michael T Smith

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Jaime Brahim

  University of Maryland, School of Dentistry

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2013
• First Posted: February 20, 2013
• Study Start: April 1, 2013
• Primary Completion: April 1, 2018
• Study Completion: June 1, 2018
• Last Updated: July 19, 2018

Record last verified: 2018-07

Locations

US (2)