Pain Response Evaluation of a Combined Intervention to Cope Effectively

Study Overview
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Brief Summary
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The purpose of this research is is to determine if the combination of non-opioid medication (duloxetine) and web-based pain-coping skills training (PCST) is beneficial for individuals with chronic musculoskeletal pain (CMP).

Detailed Description
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With this study, the study team hopes to address two important unanswered questions: (1) Does combination treatment consisting of duloxetine and web-based Cognitive Behavioral Therapy (CBT) optimize treatment outcomes? (2) Would adherence-focused guidance delivered by nurse clinician using motivational interviewing (MI) techniques enhance treatment effectiveness? This study is significant because the study team aims to optimize pain-related treatment outcomes at the primary care level where most patients with pain are managed. Importantly, the use of nurse clinician providing adherence-focused guidance (as opposed to content-focused guidance) on the continued practice (or use) of pain coping skills increases the likelihood that the study's intervention is scalable in the future. Effective, accessible and scalable psychoeducational treatments are needed to manage CMP in real world clinic settings.

Official Title
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Pain Response Evaluation of a Combined Intervention to Cope Effectively (PRECICE)

Conditions
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Chronic Pain

Intervention / Treatment
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* Drug: duloxetine
* Behavioral: Web-based Cognitive Behavioral Therapy (CBT)
* Other: Nurse-delivered Motivational Interviewing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients at the primary care clinic with daily pain for 3 months or longer affecting the low back, neck, hip, knee or widespread pain; at least moderate in BPI global pain severity Exclusion Criteria: uncontrolled hypertension (because duloxetine rarely increases blood pressure) active suicidal ideation planned elective surgery during the study period (to avoid the confounding effect of possible complicated post-surgery recovery course on the primary outcome) ongoing unresolved disability claims inflammatory arthritis (e.g., lupus and ankylosing spondylitis) cancer-related musculoskeletal pain pregnancy history of bipolar disorder or schizophrenia narrow angle glaucoma severe renal impairment (creatinine clearance <30) current use of duloxetine current use of any of the following medications (to avoid adverse drug-to-drug interactions): tricyclic antidepressant > 25 mg daily dose, monoamine oxidase inhibitors, fluoxetine, sertraline, paroxetine, citalopram, escitalopram, venlafaxine, milnacipran, mirtazapine, gabapentin or aripiprazole, serotonin precursors (e.g., tryptophan), and strong CYP1A2 inhibitors (e.g., ciprofloxacin, other fluoroquinolones, fluvoxamine and verapamil)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: behavioral intervention, nurse support plus medication<br>Subjects randomized to this arm will receive duloxetine, web-based Cognitive Behavioral Therapy (CBT) and nurse support. | Drug: duloxetine<br>* All participants will receive duloxetine 30 mg once daily for one week and 60 mg once daily for 24 weeks.<br>* Other names: Cymbalta;Behavioral: Web-based Cognitive Behavioral Therapy (CBT)<br>* The web-based CBT program is an automated program (i.e., users learn skills with interactive, personalized training without any therapist contact) that includes 8, 35- to 45-minute training sessions, each of which provides an educational rationale and training in cognitive or behavioral pain coping skill drawn from face-to-face CBT.<br>Other: Nurse-delivered Motivational Interviewing<br>* Subjects randomized to the duloxetine and web-based Cognitive Behavioral Therapy (CBT) with nurse support will receive 6 phone calls from MI trained nurse at week 3, 6, 10, 14, 18 and 22. Telephone sessions may run for 20 minutes on the average.<br>|
| Experimental: behavioral intervention plus medication<br>Subjects randomized to this arm will receive duloxetine and web-based Cognitive Behavioral Therapy (CBT). | Drug: duloxetine<br>* All participants will receive duloxetine 30 mg once daily for one week and 60 mg once daily for 24 weeks.<br>* Other names: Cymbalta;Behavioral: Web-based Cognitive Behavioral Therapy (CBT)<br>* The web-based CBT program is an automated program (i.e., users learn skills with interactive, personalized training without any therapist contact) that includes 8, 35- to 45-minute training sessions, each of which provides an educational rationale and training in cognitive or behavioral pain coping skill drawn from face-to-face CBT.<br>|
| Active Comparator: medication only<br>Subjects randomized to this arm will receive duloxetine only. | Drug: duloxetine<br>* All participants will receive duloxetine 30 mg once daily for one week and 60 mg once daily for 24 weeks.<br>* Other names: Cymbalta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brief Pain Inventory (BPI) | BPI score ranges from 0 to 10 with a higher score denoting a higher pain severity. | Baseline | 
| Brief Pain Inventory (BPI) | BPI score ranges from 0 to 10 with a higher score denoting a higher pain severity. | week 13 of treatment phase | 
| Brief Pain Inventory (BPI) | BPI score ranges from 0 to 10 with a higher score denoting a higher pain severity. | week 25 of treatment phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient-Reported Outcomes Measurement Information System (PROMIS) | Adult Self-Reported Measures on physical health (fatigue, pain intensity, pain interference, physical function, sleep disturbance, pain behavior and sleep-related impairment) and social health (ability to participate in social roles and activities). The values of the response to each question will be summed in order to determine the raw score. This must then be converted to the T-score. T-scores are standardized with a mean of 50 and a standard deviation of 10. I.e. a T-score of 40 would be one standard deviation lower than the mean. A higher PROMIS T-score represents more of the concept being measured. For positively-worded concepts like Physical Function a T-score of 60 is one standard deviation better than average. By comparison, a Physical Function T-score of 40 is one SD worse than average. | week 13 of treatment phase, week 25 of treatment phase | 
| The Pain Catastrophizing Scale (PCS) | 13-item scale that describes the catastrophic thoughts and feelings that people may have in response to pain. The total score ranges 0 (no catastrophizing) to 52 (severe catastrophizing). | Baseline, week 13 of treatment phase, week 25 of treatment phase | 
| Global Rating of Change | Score ranges from -5 through 5 with 5 denoting a better outcome; 0 denotes no change | Baseline, week 13 of treatment phase, week 25 of treatment phase | 
| Patient Health Questionnaire 8-Item Depression Scale (PHQ-8) | Score is the sum of the 8 items. Score ranges from 0-24. A score of 10 or greater is considered major depression, 20 or more is severe major depression. | Baseline, week 13 of treatment phase, week 25 of treatment phase | 
| Generalized Anxiety Disorder 7-item scale (GAD-7) | Score ranges from 0-24. Scores of 5, 10, and 15 are the respective cut-offs for mild, moderate, and severe anxiety. Further evaluation is recommended when a score of 10 or greater is recorded. | Baseline, week 13 of treatment phase, week 25 of treatment phase | 
| Patient Health Quality Anxiety-Depression Scale (PHQ-ADS) | PHQ-ADS is a single measure for assessing psychological distress in clinical practice and research. Scores range from 0-30. PHQ-ADS cut points of 10, 20 and 30 were shown to represent mild, moderate, and severe levels of psychological distress, respectively. | Baseline, week 13 of treatment phase, week 25 of treatment phase | 
| Frequency of Practicing Pain Coping Skills | Study team will ask participants how many days they practiced pain coping skills in the past 2 weeks (maximum of 14) | week 13 of treatment phase, week 25 of treatment phase | 
| Opioid Morphine Equivalent (OME) | The study will use self-reported opioid type, medical record-based dosage and self-reported daily frequency to calculate the OME, reported in milligrams per day. The OME is calculated by multiplying dosage by daily frequency by a conversion factor for each opioid based on opioid strength. | Baseline, week 13 of treatment phase, week 25 of treatment phase | 
| relevant concomitant medication use--non-steroidal anti-inflammatory drugs (NSAIDS) | Number of subjects who use NSAIDS between visits will be collected | week 13 of treatment phase, week 25 of treatment phase | 
| relevant concomitant medication use--muscle relaxants | Number of subjects who use muscle relaxants between visits will be collected | week 13 of treatment phase, week 25 of treatment phase | 
| Number of Subjects who use Physical Therapy between visits |  | week 13 of treatment phase, week 25 of treatment phase | 
| Number of Subjects who use occupational therapy between visits |  | week 13 of treatment phase, week 25 of treatment phase | 
| Number of Subjects who use acupuncture between visits |  | week 13 of treatment phase, week 25 of treatment phase | 
| Number of Subjects who use massage between visits |  | week 13 of treatment phase, week 25 of treatment phase | 
| Number of Subjects who go to a chiropractor between visits |  | week 13 of treatment phase, week 25 of treatment phase | 
| Number of Subjects who go to a pain specialist between visits |  | week 13 of treatment phase, week 25 of treatment phase | 
| Number of Subjects who use pain psychologist between visits |  | week 13 of treatment phase, week 25 of treatment phase | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-opioid pain medication, psychoeducational treatments, chronic musculoskeletal pain