An Internet-based Multimodal Pain Program for Chronic Temporomandibular Disorder Pain
Condition: Chronic Pain; Temporomandibular Disorder
MeSH terms: Temporomandibular Joint Disorders; Temporomandibular Joint Dysfunction Syndrome; Chronic Pain
Study type: Interventional

Summary: 
      Background Chronic temporomandibular disorders (TMD) pain is an undertreated condition in
      Sweden despite the fact that national guidelines includes effective treatment options. These
      guidelines recommend multimodal treatment with a behavioral approach. Internet-based
      intervention is an appealing modality for multimodal TMD treatment, enabling more patients to
      be reached and treated.

      Objective To investigate the treatment effect of an internet-based multimodal pain program
      (iMPP) on chronic TMD pain. As the study progressed, it also became a measure to evaluate the
      feasibility of running a larger randomized controlled trial.
    

Detailed description: 
      BACKGROUND Chronic temporomandibular disorders (TMD) pain is an undertreated condition in
      Sweden despite the fact that national guidelines includes effective treatment options. These
      guidelines recommend multimodal treatment with a behavioral approach. Internet-based
      intervention is an appealing modality for multimodal TMD treatment, enabling more patients to
      be reached and treated.

      Objective To investigate the treatment effect of an internet-based multimodal pain program
      (iMPP) on chronic TMD pain. As the study progressed, it also became a measure to evaluate the
      feasibility of running a larger randomized controlled trial.

      STUDY DESIGN An unblinded parallel-arm RCT pilot study with equal allocation was conducted.
      Participants were randomized to the iMPP or to an active control. They were recruited from a
      general dental care clinic (Fäladstorget) within the National Dental Care Skåne, Sweden.
      Examination and allocated treatment were free of charge for participants and no other
      financial compensation was given. This study is part of a large research project with the
      primary objective to study changes in the brain after treatment in patients with chronic TMD
      pain. Therefore, participants went through magnetic resonance imaging (MRI) of the brain pre-
      and post-treatment. The study was approved by the Ethics Review Board in Lund, Sweden (No.
      2016/6). This study was not registered in a public trials registry due to its feasibility
      character.

      PARTICIPANTS Participants had to fulfill the following criteria: (1) age between 18 and 75
      years; (2) at least one of the TMD pain diagnoses myalgia, myofascial pain with referral,
      headache attributed to TMD or arthralgia according to the Diagnostic Criteria for
      Temporomandibular Disorders (DC/TMD) {Schiffman, 2014 #4}; (3) chronic TMD pain (≥3 months),
      experienced once a week or more often, with an intensity of ≥3 on an 0-10 numeric rating
      scale (NRS); (4) access to a computer with an internet connection and a mobile phone; (5)
      sufficient computer literacy and (6) mastery of the Swedish language. Exclusion criteria
      were: (1) chronic inflammatory systemic disease; (2) all psychiatric disorders except
      depression and anxiety (due to high comorbidity); (3) occlusal splint therapy in the past 12
      months; (4) ongoing extensive dental treatment; and (5) conditions contradicting MRI
      examination.

      Recruitment of participants started in April 2016 and ended in December 2017. Screening was
      paused during holiday periods (June-August) and during February-April in 2017 due to
      technical issues with the MRI machine.

      PROCEDURE To identify potential participants, all consecutive adult patients visiting for a
      regular dental check-up were screened. If eligible for the inclusion examination and
      interested in participation oral and written information about the study was given and a new
      appointment was booked. The inclusion examination was performed and written informed consent
      was received. Permuted block randomization with a fixed block size of ten was used. If
      allocated to iMPP, the participants received working material by mail and the URL to the
      program was sent by email. Treatment start was assisted by phone. If allocated to treatment
      with occlusal splint, alginate impressions and index were prepared at the same appointment as
      the inclusion examination and a new appointment was booked for delivering the splint.
      Follow-up was performed at three and six months after treatment start by questionnaires sent
      by mail. Participants also went through an MRI of the brain at baseline (after randomization
      but before treatment start) and at six months after treatment start at Skåne University
      Hospital, Malmö, Sweden.

      SCREENING The TMD screening tool 2Q/TMD was used to check for initial eligibility {Lövgren,
      2016 #293} {Lövgren, 2016 #277}. The screening questions were (Q1) "Do you have pain in your
      temple, face, jaw or jaw joint once a week or more?" and (Q2) "Do you have pain once a week
      or more when you open your mouth or chew?". Participants had to answer yes to at least one of
      the questions and also not fulfill any of the exclusion criteria previously mentioned to be
      eligible for the inclusion examination.

      INCLUSION EXAMINATION All participants underwent a standardized examination according to the
      DC/TMD to control for eligibility and to collect baseline data. The DC/TMD includes a
      clinical examination and questionnaires described below {Schiffman, 2014 #4}. Demographic
      data and pre-treatment expectancies on allocated treatment were also assessed.

      CLINICAL EXAMINATION The clinical DC/TMD examination comprises a standardized assessment of
      pain and headache locations, mouth opening capacity, pain on mandibular movement, pain on
      palpation, including the presence of referred pain on palpation and temporomandibular joint
      noises. The clinical examinations were carried out by one of two general dentists calibrated
      by the DC/TMD Training and Calibration Center at Malmö University, Sweden {Vilanova, 2015
      #1}. Re-calibration of the dentists was performed mid-way through the recruitment phase.

      The DC/TMD Symptom Questionnaire was used to assess pain symptoms involving the jaw, jaw
      noise and locking and headache. Data from this questionnaire were combined with the findings
      in the clinical examination for diagnosis according to DC/TMD {Schiffman, 2014 #4}.

      QUESTIONNAIRES Pain The Graded Chronic Pain Scale was used to assess the subdomains
      characteristic pain intensity (CPI; mean of pain intensity for reported worst, current and
      average pain) and pain-related disability (DS; mean of how much facial pain changed the
      patient's ability to participate in daily activities, social activities and work). The
      questionnaire includes the assessment of pain intensity and pain-related disability that are
      scored on a 0-10 NRS (modified from{Von Korff, 2011 #279}).

      A full-body pain drawing was used to assess pain locations and distribution {Pain, 2020
      #278}. The pain distribution was categorized as local (in face area), (iii) regional pain
      (pain in the neck area in addition to local pain) and (iv) widespread pain (pain at any other
      site of the body in addition to local or regional pain.

      Physical functioning The Jaw Functional Limitation Scale (JLFS-8) was used to assess the
      overall functional limitation of the masticatory system {Ohrbach, 2008 #280}. The Oral
      Behaviors Checklist was used to assess the self-reported frequency of oral parafunctional
      behaviors during awake time {Markiewicz, 2006 #281}.

      Emotional functioning The Patient Health Questionnaire was used to assess depression and the
      Patient Health Questionnaire-15 was used to assess non-specific physical symptoms {Kroenke,
      2001 #282}{Kroenke, 2002 #283}. Anxiety was assessed with the Generalized Anxiety Disorders
      Assessment-7 {Spitzer, 2006 #285}. Stress was assessed with the Perceived Stress Scale-10 and
      the Pain Catastrophizing Scale was used to assess catastrophizing {Nordin, 2013
      #286}{Sullivan, 1995 #287}.

      Patient outcome expectancy A Swedish translation of the Stanford Expectations of Treatment
      Scale (SETS) was used to assess pre-treatment expectancies on allocated treatment {Younger,
      2012 #288}.

      TREATMENT ARMS INTERVENTION The iMPP is based on CBT and self-management principles that help
      patient cope with chronic TMD pain. It was developed by orofacial pain specialists at the
      Department of Orofacial Pain and Jaw Function, Malmö University, Sweden, in collaboration
      with Psykologpartners AB (a Swedish supplier of internet-based psychological treatment).

      The iMPP translates a face-to-face therapy to a software platform program. It can be reached
      through an URL wherever an internet connection is available and access requires a 2-factor
      authentication system. A paper-back workbook with homework assignments is included in
      addition to the internet program. The iMPP consists of seven treatment modules; each
      described in Table 1 and print screens of the program is shown in Figure 1. Recurrent in each
      module was a rating of pain frequency, stress levels and life satisfaction to keep track of
      progression (Fig. 1). Seven weeks was the intended treatment duration: 1 module/week; 40
      min/module online plus time for homework assignments. However, access to the program was not
      time-limited in this pilot study.

      The iMPP was designed to be used without HCP involvement, however, in this study, guidance
      was included in order to increase adherence. A dentist (JL) provided a start-up phone call,
      follow-up phone calls after each finished module and also sent reminders if necessary. The
      dentist was also available for additional support through the chat function in the program
      (asynchronous). At the start-up phone call, participants were guided through the functions in
      the program and informed about time requirements for the treatment. Follow-up phone calls
      involved individualized support and feedback; and if participants were unreachable at
      scheduled follow-up calls, a message through the chat function was sent with the prompt to
      get in touch. The dentist who guided the treatment had received a 2-day training on
      internet-based CBT treatment arranged by Psykologpartners AB.

      CONTROL CONDITION Participants randomized to active control received a hard Michigan-type
      stabilization splint placed in the upper jaw by one of two calibrated general dentists
      {Ramfjord, 1994 #276}. The splints were made of acrylic, covered all the maxillary teeth and
      had a smooth flat surface. Within 2-6 weeks after treatment start, a check-up appointment was
      booked. At this check-up appointment, the splint was controlled and, if needed, adjusted.
      Participants were also encouraged to continue using it.

      FOLLOW-UP Follow-up was performed with questionnaires comprising a short version of the
      DC/TMD axis II instruments.

      OUTCOME MEASURES PRELIMINARY EVALUATION OF PARTICIPANT RESPONSES TO INTERVENTION Measures
      specific to TMD included in the DC/TMD were used as outcome measures, as guided by the
      Initiative on Methods, Measurement and Pain Assessment in Clinical Trials (IMMPACT). Primary
      outcomes included characteristic pain intensity, pain-related disability and physical
      functioning (CPI, DS and JFLS-8). Secondary outcomes were depression and anxiety as measures
      of emotional functioning. In addition to the IMMPACT core domains, catastrophizing and stress
      were evaluated as secondary outcomes.

      FEASIBILITY Evaluation of the feasibility of the study concerned testing the study protocol
      and estimation of recruitment and attrition rates in the current research setting. With
      preliminary results, a post hoc power and sample size calculation were performed. With
      knowledge of recruitment and attrition rate together with a new estimated sample size, a
      decision of the feasibility of performing future larger RCT could be taken. The usage metrics
      of iMPP were not assessed.

      ADVERSE EFFECTS Adverse events for iMPP treatment were collected through the follow-up phone
      calls. Also, all participants randomized to iMPP were given written information at the
      3-month follow-up about the opportunity to withdraw from the study and receive rescue
      treatment if symptoms worsened or they were not satisfied with treatment outcome.

      STATISTICAL ANALYSIS Non-parametric statistics were used due to the characteristics of the
      pain-related variables. Post-hoc power analysis with CPI as the outcome measure was
      performed. The sample size required for a parametric test on between-group comparison was
      computed and then 15% additional subjects were added since non-parametric testing will be
      used in a future RCT {GraphPad Software, 2020 #289}.

      Estimation of required sample size was based on a previous neuroimaging study to detect
      statistically significant results in functional MRI {Gracely, 2002 #290}. According to this,
      20 participants in each group should be recruited.
    

Intervention name(s): Internet-based multimodal pain program; Occlusal splint
Intervention type(s): Behavioral; Device
Intervention description(s): A guided internet-based multimodal pain program for chronic TMD pain; Occlusal splint, standard
Other intervention name(s): Internet-based cognitive behavioral program; Michigan splint
Intervention MeSH terms: Salicylic Acid
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: An unblinded parallel-arm RCT pilot study with equal allocation was conducted. Participants were randomized to the iMPP or to an active control. They were recruited from a general dental care clinic (Fäladstorget) within the National Dental Care Skåne, Sweden. Examination and allocated treatment were free of charge for participants, and no other financial compensation was given. This study is part of a large research project with the primary objective to study changes in the brain after treatment in patients with chronic TMD pain. Therefore, participants went through magnetic resonance imaging (MRI) of the brain pre- and post-treatment. Results from neuroimaging data will be presented elsewhere, however, the feasibility of this additional examination will be addressed here. The study was approved by the Ethics Review Board in Lund, Sweden (No. 2016/6).
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Treatment