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

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Pain
• Intervention / Treatment: Drug: duloxetine; Behavioral: Web-based Cognitive Behavioral Therapy (CBT); Other: Nurse-delivered Motivational Interviewing

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.

• Study Type: Interventional
• Enrollment (Estimated): 280
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Judy Hooker; Phone Number: 336-716-0186; Email: jhooker@wakehealth.edu
• Study Contact Backup: Name: Dennis C Ang, MD; Phone Number: 336-713-4504; Email: dang@wakehealth.edu

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health Department of Rheumatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: behavioral intervention, nurse support plus medication; Subjects randomized to this arm will receive duloxetine, web-based Cognitive Behavioral Therapy (CBT) and nurse support.	Drug: duloxetine; All participants will receive duloxetine 30 mg once daily for one week and 60 mg once daily for 24 weeks.; Other Names: Cymbalta; Irenka; Behavioral: 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.; Other: 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.
Experimental: behavioral intervention plus medication; Subjects randomized to this arm will receive duloxetine and web-based Cognitive Behavioral Therapy (CBT).	Drug: duloxetine; All participants will receive duloxetine 30 mg once daily for one week and 60 mg once daily for 24 weeks.; Other Names: Cymbalta; Irenka; Behavioral: 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.
Active Comparator: medication only; Subjects randomized to this arm will receive duloxetine only.	Drug: duloxetine; All participants will receive duloxetine 30 mg once daily for one week and 60 mg once daily for 24 weeks.; Other Names: Cymbalta; Irenka

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Investigators: Principal Investigator: Dennis C Ang, MD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2021
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: May 15, 2020
• First Submitted That Met QC Criteria: May 15, 2020
• First Posted (Actual): May 20, 2020

Study Record Updates

• Last Update Posted (Estimated): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: chronic musculoskeletal pain; non-opioid pain medication; psychoeducational treatments
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Chronic Pain; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Duloxetine Hydrochloride
• Other Study ID Numbers: IRB00065428

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Protecting the rights and privacy of our study participants is our first priority. After Internal Review Board approval for data sharing is obtained, a dataset that is de-identified and in accordance with HIPAA and other state and federal right to privacy laws will be developed by the investigators. Data obtained during the study will be made available beginning after publication of the main findings of the study. Notification of availability of de-identified data will be made in the acknowledgement section of all subsequent publications resulting from the study. Data will be provided in standard SAS format. Investigators interested in obtaining de-identified study data will be instructed to send a blank compact disc to the primary investigator for copying.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No