Clinical trial NCT01794624: Biobehavioral Pain Management in TMD
Official title: Biobehavioral Pain Management in TMD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Temporomandibular Joint Disorder
Keywords: TMD
TMJD
Temporomandibular Joint Disorders
Sleep Continuity Disturbance
Pain Catastrophizing
Cognitive Therapy
Behavioral Therapy
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Institute of Dental and Craniofacial Research (NIDCR)
name: University of Maryland
First posted: 2013-02-20
Enrollment: 300
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Detailed description: Temporomandibular Joint Disorder (TMJD) is a poorly understood chronic pain disorder characterized by pain and dysfunction in the jaw joint and the muscles that control jaw movement. TMJD affects up to 15% of the adult population, differentially impacts women, is linked to greater healthcare utilization, and is associated with multiple pain-related co-morbidities. Pain-related catastrophizing (i.e., the tendency to exaggerate the threat value of pain and negatively evaluate one's ability to deal with pain; CAT) and sleep continuity disturbance (i.e., disturbance in the speed with which sleep is initiated and the degree to which it is consolidated; SCD) are two well established modifiable risk factors for TMJD and other idiopathic pain conditions. SCD is defined in this protocol as at least moderate trouble initiating or maintaining sleep, which significantly impacts daytime function. SCD is common in chronic pain, including TJMD, and poor sleep predicts both the development and exacerbation of pain. CAT, a negative cognitive-emotional predilection and response to pain, prospectively predicts the onset and exacerbation of pain, as well as numerous pain-related outcomes. Surprisingly, neither the causal status nor the neurobiological mechanisms by which these factors exert their effects on clinical pain have been established. Preliminary data from our group and others suggest that CAT and SCD are independently associated with alterations in laboratory indices of pain modulation, exaggerated pain-evoked pro-inflammatory cytokine responses and amplified clinical pain.

While the effects of CAT and SCD are independent of depression and psychological distress, no longitudinal or experimental studies have evaluated the potential interplay between CAT and SCD and how this interplay contributes to pain outcomes. There is a strong theoretical reason to hypothesize interplay between these seemingly disparate constructs among patients with chronic pain. We have developed a novel, integrated theoretical framework positing that CAT and SCD influence clinical pain through shared alterations in pain modulation and key neurobiological pathways, including amplified inflammatory activity, sympathetic activity, and adrenocortical functioning. Beyond these shared mechanisms, however, we propose to determine whether presleep CAT increases autonomic and cortical arousal during sleep measured by polysomnography (PSG)-derived indices of Heart Rate Variability (HRV) and average relative power in the alpha and beta bands on quantitative electroencephalography (QEEG). 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.

In this 5 year study, 300 women with chronic TMJD and reporting at least mild trait catastrophizing and at least mild sleep continuity disturbance will complete a randomized, parallel group experiment comparing cognitive therapy for catastrophizing (CT-CAT) and behavior therapy for sleep disturbance (BT-SCD) to TMJD disease education (TMJD-ED). Subjects will be randomized in a ratio of 1:1:1 to one of the three interventions. Each subject will participate in the study for up to 30 weeks. The study includes three phases: 1) screening and baseline (up to 10 weeks), 2) intervention (approximately 7 weeks), and 3) follow-up (ends approximately 12 weeks after the final intervention visit). Assessments of outcome measures (inflammatory activity, pain modulation, clinical pain, pre-sleep cognitive arousal, cortical and autonomic arousal) will be made during the interventions and after completion of the interventions, and will be compared with baseline assessments. It is anticipated that enrollment will be completed over four years.

Eligibility criteria: Inclusion Criteria:

* 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
* Is able to understand and willing to comply with all study procedures and is available for the duration of the study

Exclusion Criteria:

* 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
* Anything that, in the opinion of the investigator, would place the subject at increased risk or preclude the subject's full compliance with or completion of the study

Primary outcomes:
measure: To investigate a proposed causal chain for TMJD pain based on changes in pain modulation, inflammatory profile and clinical pain.
timeFrame: Pain modulation and Inflammatory profile: Visit 6-8; Clinical Pain: Visit 8 to 3 month follow up
Secondary outcomes:
measure: Impact of pre-sleep cognitive arousal on autonomic and cortical arousal during sleep
timeFrame: at end of 5 year long study
measure: Determine if manipulation of TMJD pain risk factors (SCD and CAT) reduces autonomic/cortical arousal.
timeFrame: at Visit 8 per participant (day 63 +/- 1 week)
measure: Determine if BT-SCD and CT-CAT treatments alter clinical pain and inflammatory activity relative to control.
timeFrame: at Visit 6 (Day 35 +/- 2 weeks) to Visit 8 (Day 63 +/- 2 weeks) per participant
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: University of Maryland Dental School: Brotman Facial Pain Clinic
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Meidical Center: Behavioral Medicine Research Laboratory
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Jennifer A Haythornthwaite
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: Michael T Smith
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Maryland, School of Dentistry
name: Jaime Brahim
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.