Pain Reprocessing Therapy in Post-Operative Knee Pain

Phase 2

Recruiting

• Conditions: Pain, Chronic; Knee Pain Chronic

• Registration Number: NCT06800209
• Lead Sponsor: University of Colorado, Denver

Brief Summary

The goal of this clinical trial is to learn whether Pain Reprocessing Therapy (PRT) can help adults with knee pain after knee replacement surgery. The study is comparing PRT to usual care (the regular treatment people get after surgery) to see which works better for relieving pain.

The main questions the study aims to answer are:

1. Does PRT help lower pain in people who have chronic knee pain after knee surgery?

2. How do the effects of PRT compare with usual care in terms of pain relief and other factors such as anxiety, depression, and sleep?

3. How does PRT impact the brain?

Participants will:

1. Be randomly assigned to receive either PRT or usual care.

2. Complete questionnaires about their pain and health.

3. If in the PRT group, have eight weekly therapy sessions over video calls with a therapist.

4. If interested, may also take part in an optional EEG test to measure brain activity related to pain.

Detailed Description

Investigators recently developed a novel psychological treatment called Pain Reprocessing Therapy (PRT). Using a combination of cognitive, exposure-based, and somatic psychotherapy techniques, PRT aims to promote patients' reconceptualization of pain as due to reversible, non-dangerous brain activity rather than peripheral pathology. Critically, PRT aims to reduce or eliminate pain, rather than merely increase functioning.

In the first trial of PRT (N = 151), 66% of patients randomized to PRT were pain-free or nearly pain-free at post-treatment, compared to fewer than 20% of those in the placebo and usual care control groups. This trial was limited to chronic back pain and the efficacy and mechanisms of PRT for chronic post-operative knee pain are unknown. Additionally, how the effects of PRT will generalize to telehealth treatment is not known.

Developing scalable, effective, non-pharmacological chronic pain treatments and testing their efficacy in underserved populations is an urgent societal need. Accordingly, this study also tests a remotely delivered PRT intervention.

Aim 1 of this study is to test the comparative efficacy of PRT vs. usual care on pain intensity and other pain-related outcomes at post-treatment and longitudinal follow-up.

Aim 2 of this study is to test hypothesized psychological and neurobiological mechanisms of PRT with mediation analyses and longitudinal EEG neuroimaging.

Study Timeline

• Study First Submitted: 2025-01-23
• Study First Submitted QC: 2025-01-23
• Study First Posted: 2025-01-29
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-30
• Study Start: 2025-06-01
• Last Update Posted: 2025-06-04
• Primary Completion: 2025-09-30
• Study Completion: 2026-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 110

Inclusion Criteria

• Patients are deemed eligible at 3 months post-operatively if: The patient completed a primary knee replacement [surgery completed without complication and patient exhibits full mechanical joint function, as determined by the treating physician (good range of motion, stability, and wound healing; absence of swelling)] and patient reports last week average knee pain ≥ 4 of 10 on Numeric Rating Scale (NRS).
• Reported pre-operative chronic knee pain of at least 6 months duration prior to surgery
• The procedure was a primary (not a revision) knee replacement
• Proficient in English

Exclusion Criteria

• Patients who are not willing to participate in a telehealth visit.

• Patients with pre-op chronic pain but who do not have post-operative pain after the three month time period.

• Major surgery for lower extremity or spine within 1 year of the current primary TKA.

• Active suicidal ideation with intent, recent history of suicide attempt, or self-harm behaviors within the past 5 years (including non-suicidal self-harm).

• Recent history of inpatient psychiatric hospitalization within the past 5 years.

• Active, current psychosis or mania.

• Active, current substance abuse, or problems with substance abuse within the past 2 years.

• Instability in living conditions or major interfering life events:

  • Major surgery or other major medical event planned in coming 6 months.
  • Uncertain whether they will have suitable conditions for telehealth appointments over the next 2 months, including access to a computer or tablet, reliable high-speed internet, and a quiet, comfortable room that is consistently available.
  • Major, interfering changes in employment or housing anticipated over the next 6 months.

• Neurological conditions (e.g., Alzheimer's, dementia, mild cognitive impairment, Huntington's disease, multiple sclerosis, cerebral palsy). This will be case-by-case decision made by PI to determine if the condition may interfere with treatment and warrant exclusion.

• Self-reported diagnosis of an autoimmune disease (e.g., rheumatoid arthritis, polymyalgia rheumatica, scleroderma, lupus, polymyositis, or another autoimmune disorder).

• Currently or plan to be involved in lawsuits related to pain in next 6 months, currently or plan to apply for any disability payments related to the pain in next 6 months, or received legal settlement or other disability payments related to the pain over past 2 years.

EEG Exclusion Criteria (patients can still be enrolled as long as they meet all other eligibility criteria; however, they will not undergo EEG testing):

• Are unable or uncomfortable with completing a dry cap EEG.
• Has had a history of abnormal EEGs.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Pain intensity	Approximately 12, 18, and 26 weeks post-randomization	Last-week average pain intensity is assessed using the 5-item pain subscale of the 12-item shortened version (ShortMAC) of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The ShortMAC assesses pain severity and its impact on functioning. It consists of 12 total items, including 5 pain items and 7 pain interference items. The 5 pain items measure pain on a scale of 0-4, with 0 indicating no pain and 4 indicating extreme pain.

Secondary Outcome Measures

Name	Time	Method
Pain interference	Approximately 12, 18, and 26 weeks post-randomization	Pain interference is assessed using the 7-item pain interference subscale of the 12-item shortened version (ShortMAC) of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The ShortMAC assesses pain severity and its impact on functioning. It consists of 12 total items including 5 pain items and 7 pain interference items. The 7 pain interference items measure pain interference in the last week on a scale of 0-4, with 0 indicating no difficulty and 4 indicating extreme difficulty or inability to perform an activity.
Depression	Approximately 12, 18, and 26 weeks post-randomization	Depression is assessed using the 8-item depression subscale of the Patient-Reported Outcome Measurement Information System Short Form (PROMIS-SF). The PROMIS scale as a whole monitors the physical, mental, and social health of adults and children. Each item in the PROMIS-SF depression subscale is rated on a 5-point scale of 1 (never) to 5 (always).
Anxiety	Approximately 12, 18, and 26 weeks post-randomization	Anxiety is assessed using the 8-item anxiety subscale of the Patient-Reported Outcome Measurement Information System Short Form (PROMIS-SF). The PROMIS scale as a whole monitors the physical, mental, and social health of adults and children. Each item in the PROMIS-SF anxiety subscale is rated on a 5-point scale of 1 (never) to 5 (always).
Fatigue	Approximately 12, 18, and 26 weeks post-randomization	Fatigue is assessed using the 8-item sleep disturbance subscale of the Patient-Reported Outcome Measurement Information System Short Form (PROMIS-SF). The PROMIS scale as a whole monitors the physical, mental, and social health of adults and children. 7 of the 8 items in the PROMIS-SF sleep disturbance subscale are rated on a 5-point scale of 1 (not at all) to 5 (very much) while 1 item is rated on a 5-point scale of 1 (very poor) to 5 (very good).
Opioid Use	Approximately 12, 18, and 26 weeks post-randomization	Opioid Use is assessed via patient-reported medication logs

Trial Locations

Locations (2)

University of Colorado Anschutz Medical Campus; 🇺🇸 Aurora, Colorado, United States

Hospital for Special Surgery; 🇺🇸 New York, New York, United States