Moderators and Mediators (M & M Trial) of Psychosocial Treatments of Chronic Pain

Not Applicable

Recruiting

• Conditions: Back Pain; Chronic Pain; Neck Pain
• Interventions: Behavioral: Cognitive Behavioral Therapy; Behavioral: Emotional Awareness and Expression Therapy; Behavioral: Acceptance and Commitment Therapy; Other: Treatment as Usual

• Registration Number: NCT06044649
• Lead Sponsor: Rush University Medical Center

Brief Summary

Chronic musculoskeletal pain (CP) is a major public health concern. Psychosocial treatments have been shown to be efficacious when compared to largely inert control conditions, but they are characterized by modest effects on primary outcomes. One strategy to boost efficacy is to increase our understanding of treatment mediators. Studies of mediators that directly compare different treatments with each other are needed to determine which mediators are treatment-specific, which are shared across treatments, and which contribute the most to clinical outcomes. Another strategy is to identify the patient characteristics that moderate treatment responses. Research is needed that is guided by theoretical models and that tests moderators across multiple treatments. Identifying subgroups of patients more likely to respond to one or another treatment can advance precision medicine by informing a priori patient-treatment matches that can optimize treatment effects. To accomplish these goals, the authors will conduct a randomized clinical trial to compare the mediators and moderators of the clinical effects of Cognitive-Behavioral Therapy (CBT), Acceptance and Commitment Therapy (ACT), and Emotional Awareness and Expression Therapy (EAET) on adults with chronic spinal (axial) pain. Following baseline assessment of outcome variables as well as potential mediators and moderators, 460 participants will be randomized to CBT, ACT, EAET, or treatment-as-usual control (TAU). The three treatments will be conducted as individual therapy provided weekly for 8 weeks via telehealth. The researchers will conduct weekly assessments of both potential mediators and outcomes, as well as post-treatment and 6-month follow-up assessments. The goal of the study is to identify the most powerful treatment mechanisms - specific and shared -- and reveal for whom the mediator-outcome pathways are strongest.This project can increase the effects of our psychosocial chronic pain treatments by identifying the most effective treatment mechanisms and by informing patient-treatment matches that can optimize treatment effects.

Detailed Description

Chronic musculoskeletal pain (CP) is a major public health concern. A number of psychosocial treatments have emerged in recent decades to help address this problem. These interventions have been shown to be efficacious when compared to largely inert control conditions; however, recent meta-analyses indicate that most of these treatments are characterized by modest effects on primary outcomes. This is a critical shortcoming of these otherwise promising approaches. Rather than attempting to boost efficacy only by developing new and hopefully more powerful interventions, we can also look within our already proven treatments for ways to enhance the magnitude of treatment effects. One strategy is to increase our understanding of treatment mediators. Studies of mediators that directly compare different treatments with each other are needed to determine which mediators are treatment-specific, which are shared across treatments, and which contribute the most to clinical outcomes. The findings from such research could be used to inform adaptations to existing treatment that enhance their benefits. A second strategy for increasing the beneficial effects of existing treatments is to identify the patient characteristics that moderate treatment responses. Research is needed that is guided by theoretical models and that tests moderators across multiple treatments. Identifying subgroups of patients more likely to respond to one or another treatment can advance precision medicine by informing a priori patient-treatment matches that can optimize treatment effects. To accomplish these goals, we will conduct a randomized clinical trial to compare the mediators and moderators of the clinical effects of Cognitive-Behavioral Therapy (CBT), Acceptance and Commitment Therapy (ACT), and Emotional Awareness and Expression Therapy (EAET) on adults with chronic spinal (axial) pain. Following baseline assessment of outcome variables as well as potential mediators and moderators we will randomize 460 participants to CBT, ACT, EAET, or treatment-as-usual control (TAU). The three treatments will be conducted as individual therapy provided weekly for 8 weeks via telehealth. We will conduct weekly assessments of both potential mediators and outcomes, as well as post-treatment and 6-month follow-up assessments. In addition to comparing the three treatments to each other (and TAU) for overall efficacy, we focus on two specific aims: Aim 1 is to identify mediators that are specific to treatments and those that are shared across treatments. Aim 2 is to identify baseline moderators of specific treatments and general predictors across treatments. This project can increase the effects of our psychosocial chronic pain treatments by identifying the most powerful treatment mechanisms - specific and shared -- and revealing for whom the mediator-outcome pathways are strongest. Via increased understanding of mediator and moderators, more effective pain treatment approaches can be developed, tested, and implemented.

Study Timeline

• Study First Submitted: 2023-09-11
• Study First Submitted QC: 2023-09-13
• Study First Posted: 2023-09-21
• Study Start: 2023-11-15
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-24
• Last Update Posted: 2025-04-25
• Primary Completion: 2026-09-30
• Study Completion: 2027-03-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 460

Inclusion Criteria

• Back/neck is primary pain location (e.g., back/neck pain greater than leg pain)
• Pain for at least 3 months and experienced 4 or more days/week for the past 6 months
• Pain intensity last week is >= 3 (0 to 10 rating scale)
• Pain interference last week is >= 3 (0 to 10 rating scale)
• At least age 18
• Lives in United States
• Fluent in English
• Has personal computer/tablet and internet access
• Able to attend weekly sessions
• Willing to be randomized
• Seeking to improve their pain-related status via a psychological therapy

Exclusion Criteria

Past 2 years (treated for or having experienced):

• Complex regional pain syndrome
• Epilepsy/seizure disorder
• Autoimmune disease
• Liver disease
• Cancer
• Heart disease
• Substance dependence or use disorder
• Schizophrenia or other psychotic disorder
• Bipolar disorder
• Obsessive-compulsive disorder
• Borderline personality disorder
• Suicide attempt or suicide intention or impulse

Also:

• Major medical procedure scheduled within next 9 months
• Applied for/ litigating for pain-related disability/worker's compensation (past year).
• Major life event/stressor in past 6 months
• Cognitive impairment (screener score <=4)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cognitive Behavioral Therapy	Cognitive Behavioral Therapy	8-session, individual, Cognitive Behavioral Therapy delivered remotely by skilled CBT therapists
Emotional Awareness and Expression Therapy	Emotional Awareness and Expression Therapy	8-session, individual, Emotional Awareness and Expression Therapy delivered remotely by skilled EAET
Acceptance and Commitment Therapy	Acceptance and Commitment Therapy	8-session, individual, Acceptance and Commitment Therapy delivered remotely by skilled ACT therapists
Treatment As Usual	Treatment as Usual	In this control condition, participants will engage in their usual care for neck/back pain with no additional experimental intervention

Primary Outcome Measures

Name	Time	Method
Patient-Reported Outcome Measurement Information System (PROMIS) - Pain Interference - Short Form 8a	Baseline to post-treatment and 6-month follow-up, and weekly during treatment	8-item measure of pain interference over past week (range1 to 5; higher scores = more pain interference)
Brief Pain Inventory (BPI) - Pain Severity	Baseline to post-treatment and 6-month follow-up, and weekly during treatment	4-item measure of pain severity over past week (range 0 to 10; higher scores = worse pain severity)

Secondary Outcome Measures

Name	Time	Method
Patient Global Impression of Change	Weekly during treatment to post-treatment and 6-month follow-up	1-item measure of overall health change since the start of the study (range 1 to 7; higher scores = more health improvement)
Positive and Negative Affect Schedule (PANAS) - Positive Affect - Short Form	Baseline to post-treatment and 6-month follow-up, and weekly during treatment	5-item measure of positive affect in the past week (range 1 to 5; higher scores = more positive affectivity)
Posttraumatic Stress Disorder Checklist (PCL) - Short Form	Baseline to post-treatment and 6-month follow-up, and weekly during treatment	5-item measure of trauma symptoms in the past week (range 1 to 4; higher scores = worse PTSD symptoms)
Pain Stages of Change Questionnaire (PSOCQ): Preparation and action	Baseline to post-treatment and 6-month follow-up, and weekly during treatment	13-item measure on current readiness to adopt self-management for pain, Preparation and Action items only (range 1 to 5; higher scores = more ready to change)
Patient Health Questionnaire - Depression	Baseline to post-treatment and 6-month follow-up, and weekly during treatment	8-item measure of depression symptoms in the past week (range 0 to 3; higher scores = more depression symptoms)
Patient-Reported Outcome Measurement Information System (PROMIS) - Sleep Disturbance - Short Form	Baseline to post-treatment and 6-month follow-up, and weekly during treatment	4-item measure of sleep disturbance in the past week (range 1 to 5; higher scores = more sleep disturbance)
Patient-Reported Outcome Measurement Information System (PROMIS) - Physical Function - Short Form 10a	Baseline to post-treatment and 6-month follow-up, and weekly during treatment	4-item measure of current physical function (range 1 to 5; higher scores = poorer physical function)
Patient-Reported Outcome Measurement Information System (PROMIS) - Emotional Distress - Anxiety - Short Form	Baseline to post-treatment and 6-month follow-up, and weekly during treatment	4-item measure of anxiety symptoms in the past week (range 1 to 5; higher scores = more anxiety symptoms)
Patient-Reported Outcome Measurement Information System (PROMIS) - Emotional Distress - Depression - Short Form	Baseline to post-treatment and 6-month follow-up, and weekly during treatment	4-item measure of depression symptoms in the past week (range 1 to 5; higher scores = more depression symptoms)
Employment	Baseline to post-treatment and 6-month follow-up	3-item measure on current employment (options for current status and qualitative responses)
Levels of Emotional Awareness Scale (LEAS) - Forms A and B	Baseline	10-item measure of current emotional awareness (includes qualitative responses); responses coded for levels of emotional awareness; higher = greater awareness; Form A baseline and Form B at post-treatment
Inventory of Interpersonal Problems (IIP)	Baseline to post-treatment and 6-month follow-up	32-item measure of current interpersonal problems (range 0 to 4; higher scores = more interpersonal problems)
The Tobacco, Alcohol, Prescription medications, and other Substance (TAPS) Tool - Part II	Baseline to post-treatment and 6-month follow-up	9-item measure on substance use in the past week (yes/no responses); higher scores = more use
Patient-Reported Outcome Measurement Information System (PROMIS) - Fatigue - Short Form	Baseline to post-treatment and 6-month follow-up, and weekly during treatment	4-item measure of fatigue in the past week (range 1 to 5; higher scores = more fatigue)
Patient-Reported Outcome Measurement Information System (PROMIS) - Emotional Distress - Anger - Short Form 5a	Baseline to post-treatment and 6-month follow-up, and weekly during treatment	5-item measure of anger in the past week (range 1 to 5; higher scores = more anger)
Opioid Use	Baseline to post-treatment and 6-month follow-up, and weekly during treatment	1-item measure on opioid use in past 7 days (range 1 to 7; higher scores = more days)
Post-Treatment Satisfaction Questionnaire	Post-Treatment to 6-Month Follow-Up	8-item measure on patient post-treatment satisfaction (range 1 to 10; higher scores = more satisfied - also included qualitative responses)
Other Pain Treatments and Health Care Use	Baseline to post-treatment and 6-month follow-up	2-item measure of health care currently, the past 6 months, and the past 4 weeks (2 items with yes/no responses and remaining range 0 to 4; higher scores = more treatment)
American College of Rheumatology (ACR) Fibromyalgia Diagnostic Criteria - 2011	Baseline to post-treatment and 6-month follow-up	8-item measure on fibromyalgia symptoms in the past week (items with yes/no responses, a checklist, and remaining range 0 to 3; higher scores = worse fibromyalgia symptoms)
Posttraumatic Stress Disorder Checklist (PCL)	Baseline to post-treatment and 6-month follow-up	20-item measure of PTSD symptoms in the past month (range 0 to 4; higher scores = worse PTSD symptoms)
Psychological Flexibility Scale (PSYFlex)	Baseline to post-treatment and 6-month follow-up	6-item measure of psychological flexibility in the past week (range 0 to 5; higher scores = higher psychological flexibility)

Trial Locations

Locations (2)

Wayne State University; 🇺🇸 Detroit, Michigan, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States