Pragmatic Comparative Effectiveness Trial of Evidence-based, On-demand, Digital Behavioral Treatments for Chronic Pain

Not Applicable

Completed

Conditions: Chronic Pain

Registration Number: NCT04933474

Lead Sponsor: Cedars-Sinai Medical Center

Brief Summary: This study compared two available, evidence-based, at-home digital pain treatment programs. The goal is to see if one approach is better than the other, and whether certain patients respond to one more than the other. Study participants will be randomly assigned to receive one of two treatment programs: Skills-Based VR or painTRAINER. VR devices and painTRAINER manuals will be delivered to the participant's home with instructions for use via FedEx; participants will receive remote technical support. They will be followed for 12 weeks and complete Patient Reported Outcome (PRO) questionnaires to assess functional status, pain levels, and use of pain medications (including opioids). Participants will also be asked to provide consent/authorization to access medical records from their treating facility.

Detailed Description: We performed a two-arm, multi-center, virtual randomized controlled trial (vRCT) in a geographically diverse group of patients with mixed-etiology chronic pain. Using a random number generator, patients were allocated in a 1:1 ratio between two self-administered, remotely deployed CBT delivery platforms, stratified by site: (1) a 2D mHealth app called PainTRAINER; and (2) 3D virtual reality (VR) app called EaseVRx+. The primary analysis compared changes in pain intensity over two months upon completion of the standardized 8-week digital CBT protocols. Secondary outcomes include pain catastrophizing, anxiety, pain interference, self-efficacy, and opioid use. Patient blinding is not possible in VR versus non-VR studies; however, researchers exhibited equipoise when describing the competing interventions, Investigators and data analysts were blinded to patient allocation; coordinators administering the intervention were unblinded in order onboard participants to their assigned program and troubleshoot any difficulties throughout the study.

The population eligible for the study include individuals with any of more than 130 ICD codes for chronic pain conditions, including somatic, musculoskeletal, neuropathic, and visceral pain who also recorded an average pain intensity of 4 or greater on a standard 0-10 numeric rating scale (NRS) over the past week. Patients were recruited from three major sites: (1) Cedars-Sinai Health System (CSHS); (2) Ochsner Health; (3) UAB. All sites used search tools to identify participants within their respective electronic health record (EHR) with at least one of the inclusionary chronic pain ICD codes and who did not meet several coded ineligibility criteria, included but not limited to ongoing end-of-life care and an age less than 13 years old. Patients meeting preliminary eligibility were chart reviewed for confirmation, then contacted through methods approved by each respective site's IRB, which included combinations of email, physical mail, and patient-portal notifications. Patients were offered an opportunity to opt-in or opt-out, and those who do not respond were contacted by phone call to assess interest and eligibility.

This trial was conducted remotely using patient identification, screening, and monitoring processes developed by the study team and applied in many trials involving virtual reality, including other NIH-sponsored trials using VR therapies for pain (NCT04409353, NCT04907643). Participants who provided eConsent and completed a 7-day "screener week" on REDCap were randomized and sent study materials by mail. Study onboarding was performed over the phone and did not require in-person interactions with the study team.

We employed a biopsychosocial conceptual framework for monitoring outcomes in the trial, focusing on pain intensity as the primary outcome, and included a range of other relevant PROs selected in partnership with our patient partners. PROs were collected via REDCap. Pain intensity was measured using a standard 11-point numeric rating scale (NRS) with a 24-hour recall. Consistent with NIH Helping to End Addiction Long-Term (HEAL) guidance, we measured daily pain NRS for 7-days during baseline (week 0), and again during the final week of the digital program study (week 8). Intention-to-Treat (ITT) analysis of the primary endpoint involved comparing the proportion of individuals who recorded a minimally clinically importance difference (MCID) of two on the average pain NRS recorded between Week 8 and Week 0. Secondary outcomes include the 4-item short form pain catastrophizing scale, 4-item NIH PROMIS Anxiety scale, 4-item NIH PROMIS Pain Interference scale, 2-item Pain Self-Efficacy Questionnaire, and average opioid usage derived from total morphine milligram equivalents (MMEs) in self-reported medication use. In addition, VR presence and cybersickness at the start of intervention use using the Presence Scale and Simulator Sickness Questionnaire (SSQ), respectively.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 330

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Change From Baseline to Week 8 in Daily Pain Intensity	From baseline to end of treatment at Week 8	\[Alternative Title: Proportion of Participants with \>=2 Change in Average of 7 Daily Pain Intensity Questionnaires\] The change from study baseline to week 8 in daily pain intensity was measured using the standard 11-point numeric rating scale (NRS) with a 24-hour recall. Daily pain NRS was measured for 7-days during baseline and again during the final week of the study (week 8). This outcome is the baseline vs. week 8 difference-in-difference in 7-day average NRS pain intensity scores, dichotomized into if the minimally clinically importance difference (MCID) of 2 is achieved. NRS is positively scored, where higher scores indicate worse pain intensity. The difference from baseline is reported as Baseline - Week 8, therefore a higher difference corresponds to improvement of symptoms (reduced pain intensity). The difference-in-difference is dichotomized into if the MCID of 2 is achieved, reported as the proportion of participants by arm.

Secondary Outcome Measures

Name	Time	Method
Change in Patient-Reported Outcomes Measurement Information System Pain Interference 4a (PROMIS-PI) T-score	From baseline to end of treatment at Week 8	The Patient-Reported Outcomes Measurement Information System Pain Interference (PROMIS-PI) scale, version 4a, measures the consequences of pain on relevant aspects of one's life. This includes the extent to which pain hinders engagement with social, cognitive, emotional, physical, and recreational activities. Items are rated on a 5-point Likert scale from "not at all" (1) to "very much" (5), with a raw score calculated by a sum of the 4 items ranging from 4 to 20. Results are linked to a T-Score to standardize the results across a general population (a mean T-score of 50 and a standard deviation of 10). PROMIS-PI is positively scored, where higher scores indicate worse pain interference. The difference from baseline is reported as Week 8 - Baseline, therefore a negative difference corresponds to improvement of symptoms (reduced PI).
Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety T-score	From baseline to end of treatment at Week 8	The Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety scale, version 4, assesses self-reported perceptions of fear, anxious misery (worry, dread), hyperarousal, and somatic symptoms related to arousal. Items are rated Items are rated on a 5-point Likert scale from "never" (1) to "always" (5), with a raw score calculated by a sum of the 4 items ranging from 4 to 20. Results are linked to a T-Score (healthmeasures.net) to standardize the results across a general population (a mean T-score of 50 and a standard deviation of 10). PROMIS-Anxiety is positively scored, where higher scores indicate worse anxiety. The difference from baseline is reported as Week 8 - Baseline, therefore a negative difference corresponds to improvement of symptoms (reduced anxiety).
Change in 2-item Pain Self-Efficacy Questionnaire (PSEQ-2)	From baseline to end of treatment at Week 8	The Pain Self-Efficacy Questionnaire (PSEQ-2) is a two-item instrument designed to assess the extent to which people in pain believe they are presently able to work and live a normal life, despite pain. "Work" includes housework and paid and unpaid work. Items are rated on a 7-point Likert scale from "not confident at all" (0) to "completely confident" (6), with a raw score calculated by a sum of the 2 items ranging from 0 to 12. PSEQ-2 is positively scored, where higher scores indicate greater self-efficacy. The difference from baseline is reported as Week 8 - Baseline, therefore a positive difference corresponds to improvement of symptoms (greater self-efficacy).
Change in 4-item Pain Catastrophizing Scale (briefPCS)	From baseline to end of treatment at Week 8	Self-reported pain catastrophizing was measured using the 4-item Pain Catastrophizing Scale (briefPCS) questionnaire. Pain catastrophizing is a negative mental state regarding actual or anticipated pain, and includes aspects of rumination, magnification, and sense of helplessness. Pain catastrophizing is a highly potent prognostic indicator for acute analgesic use, and acute and chronic pain outcomes, yet is also highly modifiable with behavioral treatment that enhances pain self-regulation via evidence-based skills. Items are rated on a 5-point Likert scale from "not at all" (0) to "all the time" (4), with a raw score calculated by a sum of the 4 items, ranging from 0 to 16. briefPCS is positively scored, where higher scores indicate greater levels of pain catastrophizing. The difference from baseline is reported as Week 8 - Baseline, therefore a negative difference corresponds to improvement of symptoms (reduced pain catastrophizing).
Change in Weekly Opioid Use (Use or No Use)	From baseline to end of treatment at Week 8	Opioid medications are commonly prescribed for pain analgesia. Participants self-reported their prescription and over-the-counter pain medications, daily for 7 days, at baseline (days -6 to 0) and during Week 8 of the study (days 50-56). The questionnaire contains lists of opioids and non-opioids. Responses were categorized based on whether or not an individual reported the use of an opioid medication on at least one of the daily surveys during baseline and during week 8; responses are reported as the proportion of individuals who reported the use of an opioid and who completed at least 4 daily questionnaires during the specified time period, divided by the total number of individuals who completed at least 4 daily questionnaires during the time interval, by arm. A smaller proportion at week 8 corresponds to a decrease in the frequency of opioid use in the observed sample.

Trial Locations

Locations (1): Cedars-Sinai Medical Center
🇺🇸
Los Angeles, California, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States