INSPIRE: Integrated Services for Pain: Interventions to Reduce Pain Effectively

• ClinicalTrials.gov Identifier: NCT03454555
• Recruitment Status: Recruiting
• First Posted: March 6, 2018
• Last Update Posted: January 28, 2020
• Sponsor: RTI International
• Collaborators: Patient-Centered Outcomes Research Institute; University of North Carolina Health Care System; Duke University Health System; Vanderbilt University Health System
• Information provided by (Responsible Party): RTI International

Study Description

Brief Summary:

Up to one-third of Americans suffer from chronic noncancer pain (CNCP)(Institute of Medicine, 2011). Opioids are often used to treat CNCP. Once on chronic opioid therapy (COT), individuals often continue for months or years(Martin et al., 2011; Vanderlip et al., 2014). Evidence for the effectiveness of COT to treat CNCP is insufficient, exposing individuals to known risk. Strategies are needed to reduce/eliminate COT in patients who are not benefiting from opioids while ensuring access for those who are.

The researchers will employ a multisite pragmatic trial using real-time randomization to examine the comparative effectiveness of 2 approaches: a guideline-concordant pharmacotherapy approach integrated with shared decision making (SDM) (Arm 1) compared with a guideline-concordant pharmacotherapy approach integrated with motivational interviewing (MI) and cognitive behavioral therapy for chronic pain (CBT-CP) (Arm 2).

The researchers will examine the impact of the 2 approaches on several outcomes. The study will examine which set of patients have greater opioid dose reduction, improved functioning, and/or lower pain scores. Clinical outcomes will be assessed using electronic health record data at 4 timepoints: baseline, 6 months, 12 months, and 18 months. Patient-reported outcomes, including physical functioning and level of pain, will be measured via patient survey at 3 timepoints: baseline, 6 months, and 12 months.

The study will include patients from North Carolina and Tennessee. The researchers will enroll 530 patients in each study arm for a total enrollment of 1,060. This sample size will provide robust power to detect clinically important differences in reduction of opioid use between the two study arms.

Analyses will include longitudinal (mixed effects) models to compare the change in outcomes from baseline to each timepoint between the two study arms. The project team will explore differences in the intervention effect according to participant characteristics such as age, sex, baseline pain level, baseline opioid dose, physical comorbidities, mental health comorbidities, and a history of substance abuse. Qualitative research methods will be used to obtain patient input on their experiences.

Condition or disease	Intervention/treatment	Phase
Chronic Pain	Behavioral: Shared Decision Making; Behavioral: Motivational Interviewing and Cognitive Behavioral Therapy for Chronic Pain	Not Applicable

Detailed Description:

Study Design and Approach This is a large-scale randomized pragmatic trial implementing pharmacotherapy guidelines and behavioral interventions in real-world settings.

In this trial, the researchers will examine the comparative effectiveness of two approaches to reducing opioid dosages for chronic non-cancer patients (CNCP) who are on chronic opioid therapy (COT): shared decision making (SDM) and guideline-concordant pharmacotherapy (Arm 1) compared with cognitive behavioral therapy for chronic pain and motivational interviewing (CBT-CP+MI) and guideline-concordant pharmacotherapy (Arm 2).

Rationale:

• Up to one-third of Americans suffer from chronic noncancer pain (CNCP) (Institute of Medicine, 2011).
• Opioids are often used to treat CNCP. Once on chronic opioid therapy (COT), individuals often continue with this class of medication for years (Martin et al., 2011; Vanderlip et al., 2014).
• Evidence for the effectiveness of COT to treat CNCP is limited, exposing individuals to known risks (Chou et al., 2014).
• Modified or novel pharmacological and nonpharmacological strategies are needed to improve pain management and promote informed decision making regarding possible opioid dose reduction.
• This project will evaluate two nonpharmacologic approaches to pain management and opioid reduction in primary care and specialty pain clinics.
• The approaches are designed to educate medical care providers and patients currently being treated for CNCP, help patients address pain and pain coping skills, and enhance patient motivation to reduce or discontinue opioid use
• This study will determine the feasibility, effectiveness and potential scalability of these interventions in reducing opioid use in patients who are using ≥ 20 morphine equivalent doses [MED]).
• The study will also assess patient acceptability of the interventions including involvement in their implementation and willingness to incur out-of-pocket costs associated with the visits.

Objectives:

To conduct a multisite pragmatic trial of two active interventions: shared decision making (SDM) as compared with cognitive behavioral therapy for chronic pain with motivational interviewing (MI+CBT-CP).

Primary Objective

• To assess if the interventions result in opioid dose reduction and compare their effectiveness.

Secondary Objectives

• To examine the impact of the interventions on physical function.
• To examine the impact of the interventions on pain interference.

Timeline:

The project commenced in February 2018. Study recruitment began in June 2019.

Recruitment, Screening, Enrollment, and Randomization:

The proposed study will enroll 530 participants in each arm, from primary care and pain clinics at three medical centers. Participants must be receiving high-dose COT for chronic non-cancer pain (CNCP) as evidenced by current or most recent prescription of an average daily morphine-equivalent dose (MED) of 20 mg or greater for CNCP.

Patient recruitment will occur on a rolling basis beginning in June 2019 and will last for up to 26 months. Delivery of the intervention will also occur on a rolling basis with the recruitment process. Patients who are potentially eligible will be identified through electronic health records (EHRs) and contacted with an invitation to participate. Interested patients will be met at their next clinic visit by a Research Coordinator to complete screening, enrollment, and randomization.

The study will use real-time randomization to limit participant loss prior to treatment. Eligible patients will be randomized using a stratified, permuted-block design, as this constrained randomization approach ensures balance between treatment groups within each of the 3 clinical institutions (our only stratification factor) at the completion of each block. Patients will be provided study information based on their treatment assignment.

Interventions:

In Arm 1, patients and clinicians will engage in Shared Decision Making (SDM). In Arm 2, patients will participate in cognitive behavioral therapy for chronic pain (CBT-CP) and motivational interviewing (MI).

Patients in both study arms will receive guideline-concordant pharmacotherapy treatment, based on clinical guidelines for opioid therapy for CNCP.

Data Collection We will employ a comprehensive, multi-mode data collection method that includes the collection of patient-reported outcomes through Web-based and phone-based surveys, and that leverages existing harmonized EHR data. We will use validated measures to measure the impact of the interventions.

We will assess our primary outcomes using EHR data from 4 timepoints: baseline, 6 months, 12 months, and 18 months. Reduction of opioid use will be measured as prescribed milligrams of daily morphine equivalent.

We will measure our secondary outcomes using patient-reported outcomes. Patient-reported outcomes, including physical functioning and level of pain, will be measured via patient survey at 3 timepoints: baseline, 6 months, and 12 months.

Data Analysis and Reporting:

In a large pragmatic trial such as the one planned, the probability is small that the groups will have imbalance by age, sex, health behaviors, or other measured or unmeasured possible confounding factors. Nevertheless, researchers will assess whether randomization has successfully created comparable groups by descriptively comparing their baseline demographic characteristics and potential confounders, including baseline pain score, comorbidities, opioid dosage, and number and type of CNCP conditions.

Researchers will evaluate clinical outcomes and patient-reported outcomes using longitudinal analyses. Analyses will use longitudinal (mixed effects) models to compare opioid dose over 18 months between the two study arms. Researchers also will explore differences in the intervention effect according to participant characteristics, such as age, sex, baseline pain level, baseline opioid dose, and the presence of physical comorbidities, mental health comorbidities, or a history of substance abuse.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1060 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Participants will be randomly assigned to one of two intervention arms for the duration of the study. The study will use real-time randomization to limit participant loss prior to treatment. Eligible patients will be randomized using a stratified, permuted-block design, as this constrained randomization approach ensures balance between treatment groups within each of the 3 clinical institutions (our only stratification factor) at the completion of each block. Consequently, throughout the trial, the treatment arms will have approximately equal sample sizes both within a site and across the study.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Integrated Health Services to Reduce Opioid Use While Managing Chronic Pain
• Actual Study Start Date: June 21, 2019
• Estimated Primary Completion Date: September 30, 2022
• Estimated Study Completion Date: September 30, 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Arm 1; Arm 1 patients will receive guideline-concordant pharmacotherapy based on clinical guidelines for opioid therapy for chronic noncancer pain plus the Shared Decision-Making (SDM) intervention.	Behavioral: Shared Decision Making; The Shared Decision Making (SDM) intervention is a behavioral intervention to explore and compare treatment options, assess a patient's values and preferences, and reach a shared decision. The intervention will have both clinician and patient components. The content of the clinician component will be based on the AHRQ (Agency for Healthcare Research and Quality) SHARE Approach, which is a 5-step process for shared decision making that includes exploring and comparing the benefits, harms, and risks of each option through meaningful dialogue about what matters most to the patient (Agency for Healthcare Research and Quality, 2017) . Patients randomized to Arm 1 will have their study visits and opioid use managed by an SDM-trained clinician at their practice.
Active Comparator: Arm 2; Arm 2 patients will receive the guideline-concordant pharmacotherapy based on clinical guidelines for opioid therapy for chronic noncancer pain plus the Motivational Interviewing and Cognitive Behavioral Therapy for Chronic Pain (MI+CBT+CP) Intervention.	Behavioral: Motivational Interviewing and Cognitive Behavioral Therapy for Chronic Pain; The Motivational Interviewing and Cognitive Behavioral Therapy for Chronic Pain intervention is an empirically based behavioral pain management behavioral therapy intervention (Monticone et al., 2015), including MI to enhance motivation for opioid dose reduction or cessation and CBT-CP for pain coping skills enhancement. We anticipate one MI session that will focus on engaging, focusing, evoking, and planning. We anticipate 8 sessions of CBT-CP, as is standard, delivered in a group setting.

Outcome Measures

Primary Outcome Measures :

1. Reduction of opioid use [ Time Frame: Baseline ]
   Average daily opioid dose in milligrams of morphine equivalent. Briefly, total morphine equivalents for each prescription will be calculated by multiplying the quantity of each prescription by the strength of the prescription (milligrams of opioid per unit dispensed). The quantity-strength product is then multiplied by conversion factors derived from published sources to estimate the milligrams of morphine equivalent to the opioids dispensed in the prescription. The total average dose in morphine equivalents per day supplied is calculated by summing the morphine equivalents for each prescription filled during a given period, and dividing by the number of days supplied. Prescribing data are derived from electronic health records (EHRs).
2. Reduction of opioid use [ Time Frame: 6 months ]
   Average daily opioid dose in milligrams of morphine equivalent. Briefly, total morphine equivalents for each prescription will be calculated by multiplying the quantity of each prescription by the strength of the prescription (milligrams of opioid per unit dispensed). The quantity-strength product is then multiplied by conversion factors derived from published sources to estimate the milligrams of morphine equivalent to the opioids dispensed in the prescription. The total average dose in morphine equivalents per day supplied is calculated by summing the morphine equivalents for each prescription filled during a given period, and dividing by the number of days supplied. Prescribing data are derived from electronic health records (EHRs).
3. Reduction of opioid use [ Time Frame: 12 months ]
   Average daily opioid dose in milligrams of morphine equivalent. Briefly, total morphine equivalents for each prescription will be calculated by multiplying the quantity of each prescription by the strength of the prescription (milligrams of opioid per unit dispensed). The quantity-strength product is then multiplied by conversion factors derived from published sources to estimate the milligrams of morphine equivalent to the opioids dispensed in the prescription. The total average dose in morphine equivalents per day supplied is calculated by summing the morphine equivalents for each prescription filled during a given period, and dividing by the number of days supplied. Prescribing data are derived from electronic health records (EHRs).
4. Reduction of opioid use [ Time Frame: 18 months ]
   Average daily opioid dose in milligrams of morphine equivalent. Briefly, total morphine equivalents for each prescription will be calculated by multiplying the quantity of each prescription by the strength of the prescription (milligrams of opioid per unit dispensed). The quantity-strength product is then multiplied by conversion factors derived from published sources to estimate the milligrams of morphine equivalent to the opioids dispensed in the prescription. The total average dose in morphine equivalents per day supplied is calculated by summing the morphine equivalents for each prescription filled during a given period, and dividing by the number of days supplied. Prescribing data are derived from electronic health records (EHRs).

Secondary Outcome Measures :

1. Physical functioning [ Time Frame: Baseline ]
   PROMIS-PF (Patient-Reported Outcomes Measurement Information System Physical functioning). Assesses self-reported capability rather than actual performance of physical activities. Patient-reported outcome.
2. Physical functioning [ Time Frame: 6 months ]
   PROMIS-PF (Patient-Reported Outcomes Measurement Information System Physical functioning). Assesses self-reported capability rather than actual performance of physical activities. Patient-reported outcome.
3. Physical functioning [ Time Frame: 12 months ]
   PROMIS-PF (Patient-Reported Outcomes Measurement Information System Physical functioning). Assesses self-reported capability rather than actual performance of physical activities. Patient-reported outcome.
4. Pain interference on functioning [ Time Frame: Baseline ]
   PROMIS-PI (Pain Interference), 8-item Short Form. Assesses extent to which pain interferes with daily functioning. Items measured on 5-point Likert scale. Patient-reported outcome.
5. Pain interference on functioning [ Time Frame: 6 months ]
   PROMIS-PI (Pain Interference), 8-item Short Form. Assesses extent to which pain interferes with daily functioning. Items measured on 5-point Likert scale. Patient-reported outcome.
6. Pain interference on functioning [ Time Frame: 12 months ]
   PROMIS-PI (Pain Interference), 8-item Short Form. Assesses extent to which pain interferes with daily functioning. Items measured on 5-point Likert scale. Patient-reported outcome.
7. Pain Intensity [ Time Frame: Baseline ]
   PROMIS Pain Intensity Short Form, 3 items. Assesses intensity of pain over the past 7 days. Patient-reported outcome.
8. Pain Intensity [ Time Frame: 6 months ]
   PROMIS Pain Intensity Short Form, 3 items. Assesses intensity of pain over the past 7 days. Patient-reported outcome.
9. Pain Intensity [ Time Frame: 12 months ]
   PROMIS Pain Intensity Short Form, 3 items. Assesses intensity of pain over the past 7 days. Patient-reported outcome.
10. Emotional distress [ Time Frame: Baseline ]
    PROMIS Emotional Distress - Anxiety, 4-items Short Form. Assesses generalized anxiety/distress over the past 7 days. Items measured on 5-point Likert scale. Patient-reported outcome.
11. Emotional distress [ Time Frame: 6 months ]
    PROMIS Emotional Distress - Anxiety, 4-items Short Form. Assesses generalized anxiety/distress over the past 7 days. Items measured on 5-point Likert scale. Patient-reported outcome.
12. Emotional distress [ Time Frame: 12 months ]
    PROMIS Emotional Distress - Anxiety, 4-items Short Form. Assesses generalized anxiety/distress over the past 7 days. Items measured on 5-point Likert scale. Patient-reported outcome.
13. Depressive symptoms [ Time Frame: Baseline ]
    PROMIS Emotional Distress - Depression, 4-item Short Form. Assesses depressive symptoms over the past 7 days. Items measured on 5-point Likert scale. Patient-reported outcome.
14. Depressive symptoms [ Time Frame: 6 months ]
    PROMIS Emotional Distress - Depression, 4-item Short Form. Assesses depressive symptoms over the past 7 days. Items measured on 5-point Likert scale. Patient-reported outcome.
15. Depressive symptoms [ Time Frame: 12 months ]
    PROMIS Emotional Distress - Depression, 4-item Short Form. Assesses depressive symptoms over the past 7 days. Items measured on 5-point Likert scale. Patient-reported outcome.
16. Satisfaction with pain care [ Time Frame: Baseline ]
    Assesses current satisfaction with pain management, 1 item. Patient-reported outcome.
17. Satisfaction with pain care [ Time Frame: 6 months ]
    Assesses current satisfaction with pain management, 1 item. Patient-reported outcome.
18. Satisfaction with pain care [ Time Frame: 12 months ]
    Assesses current satisfaction with pain management, 1 item. Patient-reported outcome.
19. Brief Pain Inventory [ Time Frame: Baseline ]
    Brief Pain Inventory (BPI) short form, 11 items. Asks for numeric ratings of pain intensity and pain interference. Patient-reported outcome.
20. Brief Pain Inventory [ Time Frame: 6 months ]
    Brief Pain Inventory (BPI) short form, 11 items. Asks for numeric ratings of pain intensity and pain interference. Patient-reported outcome.
21. Brief Pain Inventory [ Time Frame: 12 months ]
    Brief Pain Inventory (BPI) short form, 11 items. Asks for numeric ratings of pain intensity and pain interference. Patient-reported outcome.
22. Satisfaction with study health information [ Time Frame: 6 months ]
    Assesses satisfaction with and use of study intervention materials. 3 items. Patient-reported outcome.
23. Satisfaction with study health information [ Time Frame: 12 months ]
    Assesses satisfaction with and use of study intervention materials. 3 items. Patient-reported outcome.
24. Non-opioid treatments [ Time Frame: Baseline ]
    Assesses treatments used to manage physical pain, 18 items. Patient-reported outcome.
25. Non-opioid treatments [ Time Frame: 6 months ]
    Assesses treatments used to manage physical pain, 18 items. Patient-reported outcome.
26. Non-opioid treatments [ Time Frame: 12 months ]
    Assesses treatments used to manage physical pain, 18 items. Patient-reported outcome.
27. Intent to taper [ Time Frame: Baseline ]
    Assesses intent to reduce the amount of opioids taken, 2 items. Patient-reported outcome.
28. Intent to taper [ Time Frame: 6 months ]
    Assesses intent to reduce the amount of opioids taken, 2 items. Patient-reported outcome.
29. Intent to taper [ Time Frame: 12 months ]
    Assesses intent to reduce the amount of opioids taken, 2 items. Patient-reported outcome.
30. Relative opioid use [ Time Frame: 6 months ]
    Assesses overall use of opioids relative to baseline. 1 item. Patient-reported outcome.
31. Relative opioid use [ Time Frame: 12 months ]
    Assesses overall use of opioids relative to baseline. 1 item. Patient-reported outcome.
32. Patient-Centered Communication [ Time Frame: Baseline ]
    Patient-Centered Communication in Cancer Care, short form, 6 items (PCC-CA-6). Assesses patients' experiences with doctors and other health professionals in 6 domains. Patient-reported outcome.
33. Patient-Centered Communication [ Time Frame: 6 months ]
    Patient-Centered Communication in Cancer Care, short form, 6 items (PCC-CA-6). Assesses patients' experiences with doctors and other health professionals in 6 domains. Patient-reported outcome.
34. Patient-Centered Communication [ Time Frame: 12 months ]
    Patient-Centered Communication in Cancer Care, short form, 6 items (PCC-CA-6). Assesses patients' experiences with doctors and other health professionals in 6 domains. Patient-reported outcome.
35. Hospitalization [ Time Frame: 6 months ]
    Assesses hospitalization and emergency department visits related to overdose, withdrawal, or self-harm. Patient-reported outcome.
36. Hospitalization [ Time Frame: 12 months ]
    Assesses hospitalization and emergency department visits related to overdose, withdrawal, or self-harm. Patient-reported outcome.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Aged 18 to 85 years
• History of chronic non-cancer pain (CNCP)
• Receiving high-dose COT for chronic non-cancer pain (CNCP) as evidenced by current or most recent prescription of an average daily morphine-equivalent dose (MED) of 20 mg or greater for CNCP.
• Receiving care at a participating clinic from a participating provider, as evidenced by at least 1 in-person visit within the past 12 months.

Exclusion Criteria:

• Not meeting the above inclusion criteria
• Opioid use is for pain directly related to an active cancer diagnosis
• Opioid use is for maintenance treatment of an opioid use disorder (OUD)
• Suicide attempt within the past 3 years
• Active suicidal ideation
• Currently receiving CBT
• Non-English speaking
• Other reason at the discretion of the investigator

Contacts and Locations

Contacts

Contact: Laura Wagner, MPH; 919-316-3802; lwagner@rti.org

Locations

United States, North Carolina

University of North Carolina Health Care System; Recruiting

Chapel Hill, North Carolina, United States, 27599

Contact: Audrina Bunton, MA, LPCS 919-843-3084 audrina_bunton@unc.edu

Principal Investigator: Paul Chelminski, MD,MPH,FACP

Sub-Investigator: Timothy Ives, PharmD,CPP,MPH

Duke University Health System; Recruiting

Durham, North Carolina, United States, 27701

Contact: Julia Jermyn 919-681-5757 Julia.jermyn@duke.edu

Principal Investigator: Li-Tzy Wu, RN, ScD, MA

Sub-Investigator: Rowena Dolor, MD, MHS

Sub-Investigator: Lynn Bowlby, MD

Sub-Investigator: Steven D Prakken, MD

United States, Tennessee

Vanderbilt University Health System; Recruiting

Nashville, Tennessee, United States, 27232

Contact: David Crenshaw, LMSW 615-343-1765 david.l.crenshaw@vumc.org

Principal Investigator: Kristin A Swygert, PhD, DPT

Sub-Investigator: Charlene Dewey, MD,Med,FACP

Sub-Investigator: Rogelio Coronado, PT, PhD

Sponsors and Collaborators

RTI International

Patient-Centered Outcomes Research Institute

University of North Carolina Health Care System

Duke University Health System

Vanderbilt University Health System

Investigators

• Principal Investigator: Lauren McCormack, PhD, MSPH; RTI International

More Information

Publications:

Agency for Healthcare Research and Quality. (2017, February). The SHARE Approach. Retrieved from http://www.ahrq.gov/professionals/education/curriculum-tools/shareddecisionmaking/index.html

Chou R, Deyo R, Devine B, Hansen R, Sullivan S, Jarvik JG, Blazina I, Dana T, Bougatsos C, Turner J. The Effectiveness and Risks of Long-Term Opioid Treatment of Chronic Pain. Evid Rep Technol Assess (Full Rep). 2014 Sep;(218):1-219. doi: 10.23970/AHRQEPCERTA218. Review.

Institute of Medicine of the National Academies. (2011). Relieving pain in America: a blueprint for transforming prevention, care, education, and research.

Martin BC, Fan MY, Edlund MJ, Devries A, Braden JB, Sullivan MD. Long-term chronic opioid therapy discontinuation rates from the TROUP study. J Gen Intern Med. 2011 Dec;26(12):1450-7. doi: 10.1007/s11606-011-1771-0. Epub 2011 Jul 13.

Monticone M, Ambrosini E, Cedraschi C, Rocca B, Fiorentini R, Restelli M, Gianola S, Ferrante S, Zanoli G, Moja L. Cognitive-behavioral Treatment for Subacute and Chronic Neck Pain: A Cochrane Review. Spine (Phila Pa 1976). 2015 Oct 1;40(19):1495-504. doi: 10.1097/BRS.0000000000001052. Review.

Vanderlip ER, Sullivan MD, Edlund MJ, Martin BC, Fortney J, Austen M, Williams JS, Hudson T. National study of discontinuation of long-term opioid therapy among veterans. Pain. 2014 Dec;155(12):2673-9. doi: 10.1016/j.pain.2014.09.034. Epub 2014 Sep 30.

• Responsible Party: RTI International
• ClinicalTrials.gov Identifier: NCT03454555
• Other Study ID Numbers: PCORI-OPD-1610-37006
• First Posted: March 6, 2018
• Last Update Posted: January 28, 2020
• Last Verified: January 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by RTI International:

Pragmatic Clinical Trial; Comparative Effectiveness Research; Analgesics, Opioid; Decision Making, Shared; Motivational Interviewing; Cognitive Therapy; Patient Reported Outcome Measures

Additional relevant MeSH terms:

Chronic Pain; Pain; Neurologic Manifestations