Chronic Pain
Conditions
Keywords
non-opioid pain medication, psychoeducational treatments, chronic musculoskeletal pain
Brief summary
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
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.
Interventions
DRUGduloxetine
All participants will receive duloxetine 30 mg once daily for one week and 60 mg once daily for 24 weeks.
BEHAVIORALWeb-based Cognitive Behavioral Therapy (CBT)
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.
OTHERNurse-delivered Motivational Interviewing
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.
Sponsors
National Institute of Nursing Research (NINR)
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The project manager, who is blinded of treatment group assignment, has the primary responsibility of collecting outcome data throughout the study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brief Pain Inventory (BPI) Total Pain Severity | Baseline | BPI score ranges from 0 to 10 with a higher score denoting a higher pain severity. |
| Brief Pain Inventory (BPI) | week 25 of treatment phase | BPI score ranges from 0 to 10 with a higher score denoting a higher pain severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient-Reported Outcomes Measurement Information System (PROMIS) - Physical Function | week 25 of treatment phase | Adult Self-Reported Measures on physical function. The values of the response to each physical function 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. |
| Patient Health Questionnaire 8-Item Depression Scale (PHQ-8) | week 25 of treatment phase | 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. |
| Generalized Anxiety Disorder 7-item Scale (GAD-7) | week 25 of treatment phase | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Behavioral Intervention, Nurse Support Plus Medication Subjects randomized to this arm will receive duloxetine, web-based Cognitive Behavioral Therapy (CBT) and nurse support.
duloxetine: All participants will receive duloxetine 30 mg once daily for one week and 60 mg once daily for 24 weeks.
Web-based Cognitive Behavioral Therapy (CBT): 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.
Nurse-delivered Motivational Interviewing: 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. | 93 |
| Behavioral Intervention Plus Medication Subjects randomized to this arm will receive duloxetine and web-based Cognitive Behavioral Therapy (CBT).
duloxetine: All participants will receive duloxetine 30 mg once daily for one week and 60 mg once daily for 24 weeks.
Web-based Cognitive Behavioral Therapy (CBT): 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. | 93 |
| Medication Only Subjects randomized to this arm will receive duloxetine only.
duloxetine: All participants will receive duloxetine 30 mg once daily for one week and 60 mg once daily for 24 weeks. | 94 |
| Total | 280 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 8 | 9 | 5 |
| Overall Study | missed appointment | 7 | 4 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 1 | 3 |
Baseline characteristics
| Characteristic | Behavioral Intervention, Nurse Support Plus Medication | Behavioral Intervention Plus Medication | Medication Only | Total |
|---|---|---|---|---|
| Age, Continuous | 54 years STANDARD_DEVIATION 3.2 | 56 years STANDARD_DEVIATION 3.2 | 54 years STANDARD_DEVIATION 3.1 | 55 years STANDARD_DEVIATION 3.2 |
| Brief Pain Inventory (BPI) total pain severity | 6.1 units on a scale STANDARD_DEVIATION 1.6 | 5.7 units on a scale STANDARD_DEVIATION 2.1 | 5.8 units on a scale STANDARD_DEVIATION 1.8 | 5.9 units on a scale STANDARD_DEVIATION 1.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 39 Participants | 38 Participants | 39 Participants | 116 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 4 Participants | 4 Participants | 11 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 51 Participants | 51 Participants | 51 Participants | 153 Participants |
| Region of Enrollment United States | 93 participants | 93 participants | 94 participants | 280 participants |
| Sex: Female, Male Female | 65 Participants | 64 Participants | 60 Participants | 189 Participants |
| Sex: Female, Male Male | 28 Participants | 29 Participants | 34 Participants | 91 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 93 | 0 / 93 | 0 / 94 |
| other Total, other adverse events | 0 / 93 | 0 / 93 | 0 / 94 |
| serious Total, serious adverse events | 0 / 93 | 0 / 93 | 0 / 94 |
Outcome results
Primary
Brief Pain Inventory (BPI)
BPI score ranges from 0 to 10 with a higher score denoting a higher pain severity.
Time frame: week 25 of treatment phase
Population: 18 participants in the intervention/nurse/med group did not complete week 25 visit, 14 participants from the intervention/med group did not complete week 25 visit, 9 participants from the med only group did not complete week 25 visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Behavioral Intervention, Nurse Support Plus Medication | Brief Pain Inventory (BPI) | 3.5 score on a scale | Standard Error 0.26 |
| Behavioral Intervention Plus Medication | Brief Pain Inventory (BPI) | 3.7 score on a scale | Standard Error 0.25 |
| Medication Only | Brief Pain Inventory (BPI) | 3.6 score on a scale | Standard Error 0.25 |
Primary
Brief Pain Inventory (BPI) Total Pain Severity
BPI score ranges from 0 to 10 with a higher score denoting a higher pain severity.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Behavioral Intervention, Nurse Support Plus Medication | Brief Pain Inventory (BPI) Total Pain Severity | 6.1 score on a scale | Standard Deviation 1.6 |
| Behavioral Intervention Plus Medication | Brief Pain Inventory (BPI) Total Pain Severity | 5.7 score on a scale | Standard Deviation 2.1 |
| Medication Only | Brief Pain Inventory (BPI) Total Pain Severity | 5.8 score on a scale | Standard Deviation 1.8 |
Primary
Brief Pain Inventory (BPI) Total Pain Severity
BPI score ranges from 0 to 10 with a higher score denoting a higher pain severity.
Time frame: week 13 of treatment phase
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Behavioral Intervention, Nurse Support Plus Medication | Brief Pain Inventory (BPI) Total Pain Severity | 3.7 score on a scale | Standard Error 0.26 |
| Behavioral Intervention Plus Medication | Brief Pain Inventory (BPI) Total Pain Severity | 3.8 score on a scale | Standard Error 0.25 |
| Medication Only | Brief Pain Inventory (BPI) Total Pain Severity | 3.8 score on a scale | Standard Error 0.25 |
Secondary
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.
Time frame: week 25 of treatment phase
Population: 18 participants in the intervention/nurse/med group did not complete week 25 visit, 14 participants from the intervention/med group did not complete week 25 visit, 9 participants from the med only group did not complete week 25 visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Behavioral Intervention, Nurse Support Plus Medication | Generalized Anxiety Disorder 7-item Scale (GAD-7) | 3.8 score on a scale | Standard Error 0.41 |
| Behavioral Intervention Plus Medication | Generalized Anxiety Disorder 7-item Scale (GAD-7) | 3.7 score on a scale | Standard Error 0.4 |
| Medication Only | Generalized Anxiety Disorder 7-item Scale (GAD-7) | 4.0 score on a scale | Standard Error 0.39 |
Secondary
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.
Time frame: week 25 of treatment phase
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Behavioral Intervention, Nurse Support Plus Medication | Patient Health Questionnaire 8-Item Depression Scale (PHQ-8) | 5.7 score on a scale | Standard Error 0.52 |
| Behavioral Intervention Plus Medication | Patient Health Questionnaire 8-Item Depression Scale (PHQ-8) | 6.6 score on a scale | Standard Error 0.5 |
| Medication Only | Patient Health Questionnaire 8-Item Depression Scale (PHQ-8) | 6.1 score on a scale | Standard Error 0.49 |
Secondary
Patient-Reported Outcomes Measurement Information System (PROMIS) - Physical Function
Adult Self-Reported Measures on physical function. The values of the response to each physical function 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.
Time frame: week 25 of treatment phase
Population: 18 participants in the intervention/nurse/med group did not complete week 25 visit, 14 participants from the intervention/med group did not complete week 25 visit, 9 participants from the med only group did not complete week 25 visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Behavioral Intervention, Nurse Support Plus Medication | Patient-Reported Outcomes Measurement Information System (PROMIS) - Physical Function | 39.73 T score | Standard Error 0.82 |
| Behavioral Intervention Plus Medication | Patient-Reported Outcomes Measurement Information System (PROMIS) - Physical Function | 40.2 T score | Standard Error 0.79 |
| Medication Only | Patient-Reported Outcomes Measurement Information System (PROMIS) - Physical Function | 41.0 T score | Standard Error 0.77 |