Procedural Framing and Epidural Steroid Injection Outcomes (PROFESS)

The Effect of Procedural Framing on Epidural Steroid Injection Outcomes: A Randomized Controlled Study

Back pain is the leading cause of disability and military medical boards across the globe. Epidural steroid injections (ESI) are the most commonly performed pain procedure in the world.

There is strong evidence that the placebo effect for all pain treatments, including ESI, is greater than the intrinsic effect. The placebo effect is highly dependent on a patient's 'expectations', and therefore how the procedure is framed.

This study aims to compare ESI when the procedure is framed very positively- as is often done in clinical practice vs. more neutrally (which is less commonly done in clinical practice but consistent with evidence). The placebo effect is also stronger for procedures than medications. The evidence on the benefits of ESI is highly dependent on whether it is compiled by interventional doctors who perform the procedure or non-interventional researchers.

In order to determine how 'framing' a treatment affects pain outcomes, the investigative team will conduct a 3-arm randomized trial comparing positive framing of ESI, neutral framing of ESI, and medications, in patients with lumbosacral radiculopathy.

Study Overview

• Status: Recruiting
• Conditions: Lumbosacral Radiculopathy
• Intervention / Treatment: Behavioral: Behavioral manipulation of ESI expectations; Other: No behavioral manipulation of ESI expectations; Other: No behavioral manipulation of pharmacotherapy expectations

Detailed Description

Two hundred and ten eligible individuals will be randomized in blocks of 10 in a 2:2:1 ratio to receive positive framing for ESI (treatment group), neutral framing for ESI (control group), or pharmacological therapy and instructions to exercise (active control group), respectively. There will suballocation based on whether the patient has unilateral or bilateral pain (i.e., whether the participant would receive a transforaminal ESI or an interlaminar ESI, respectively). This is because there may be differences in outcomes (transforaminal injections for unilateral pain may be more effective than an interlaminar injection for bilateral pain), as well as possible differences in side effects.

For the 84 individuals randomized to the study group (positive framing of ESI), the investigators will provide 5 slides with bullet points and images outlining peer-reviewed studies, reviews and guidelines on ESI that present the treatment in a more positive light (consistent with the views of most people who perform ESIs), but still consistent with evidence. These slides will contain references to high-quality articles and there will be an investigator present to answer questions. There is a very wide range in how a procedure is presented to patients, and this framework is consistent with how ESI are presented to patients by pain practitioners from all over the world. This material is all publicly available but has been compiled in presentation form.

For the 84 individuals in the ESI control group, the investigative team will provide a 1-slide overview on ESI that is slightly less optimistic, consistent with how many non-pain-physicians view ESI including that the evidence for surgery reduction is questionable.

For the 42 individuals in the active control group who will receive a first-line medication for neuropathic and non-structured instructions to exercise, the investigators will provide a 1-side overview that presents the raw, neutral facts on adjuvants for sciatica (some guidelines recommend them, others do not, but some recommend a trial of conservative care for back pain before interventions; there are no medications across the globe approved for lumbosacral radiculopathy).

• Study Type: Interventional
• Enrollment (Estimated): 210
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jordan Wood, BS; Phone Number: 312-695-2500; Email: Jordan.Wood1@northwestern.edu
• Study Contact Backup: Name: Steven P Cohen, MD; Phone Number: 312-695-2500; Email: steven.cohen@northwestern.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University
      • Contact: Jordan Wood, BS; Phone Number: 3126952500; Email: Jordan.Wood1@northwestern.edu
      • Contact: Steven P Cohen, MD; Phone Number: 312-695-2500; Email: steven.cohen@northwestern.edu
  • Maryland
    • Bethesda, Maryland, United States, 20814
      • Enrolling by invitation
      • Walter Reed National Military Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age > 18
• Lumbosacral radicular pain based on history and physical exam (e.g. pain radiating into one or both lower extremities, sensory loss, muscle weakness, positive straight leg raising test etc.)
• Duration of pain >6 weeks
• NRS leg pain score > 4 (or if 3/10, greater or equal to back pain)
• MRI evidence of spinal pathology consistent with symptoms
• Candidates for ESI and pharmacotherapy

Exclusion Criteria:

• Untreated coagulopathy
• Previous spine surgery
• No MRI or non-concordant MRI study
• Leg pain > 15 years duration
• Epidural steroid injection within past 2 years
• Signs or symptoms of cauda equina syndrome
• Previous failed trials with gabapentin and pregabalin and tricyclic antidepressants and duloxetine
• Allergic reactions to contrast dye prohibiting injection (e.g., tranforaminal ESI), gabapentinoids, tricyclic antidepressants or duloxetine, and contraindications to all of the above medications
• Referrals from surgery for diagnostic injections for surgical evaluation
• Serious medical (e.g. congestive heart failure) or psychiatric (untreated depression) condition that might preclude optimal outcome
• Pregnancy
• Inability to understand basic English

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Positive framing- ESI; Patients will review around 5 slides detailing ESI in a very positive light and references, with study personnel available to answer questions.	Behavioral: Behavioral manipulation of ESI expectations; 5-slide summary of ESI portrayed in a positive light, accompanied by a study investigator.
Placebo Comparator: Neutral framing- ESI; Patients will review 1 slide that portrays ESI in a neutral light.	Other: No behavioral manipulation of ESI expectations; 1-slide summary of ESI portrayed in a neutral light.
Placebo Comparator: Pharmacotherapy with gabapentin, nortriptyline and/or duloxetine; Patients will review 1 slide that portrays adjuvant medications for neuropathic pain in a neutral light.	Other: No behavioral manipulation of pharmacotherapy expectations; 1-slide summary of medications for neuropathic pain portrayed in a neutral light.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean reduction in average leg pain	Mean reduction in average leg pain on a 0-10 numerical rating pain scale over the past week. This is the study's primary endpoint. 0=no pain, 10= worst pain imaginable.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average leg pain	Average leg pain on a 0-10 numerical rating scale over the past week	4 weeks
Average back pain	Average back pain on a 0-10 numerical rating scale over the past week	4 weeks
Worst leg pain	Worst leg pain on a 0-10 numerical rating scale over the past week	4 weeks
Worst back pain	Worst back pain on a 0-10 numerical rating scale over the past week	4 weeks
Analgesic medication reduction	>20% reduction in opioids or cessation of non-opioid analgesic	4 weeks
Patient global impression of change (PGIC)	Patient satisfaction with ESI on 1-7 Likert scale (1= no change, 3= a little better, 4= somewhat better 5= moderately better, 7= a great deal better)	4 weeks
Positive categorical outcome	>/=30% reduction in average leg pain (or worst leg pain if average leg pain </=4) with a PGIC >4	4 weeks
Average leg pain	Average leg pain on a 0-10 numerical rating scale over the past week	12 weeks
Average back pain	Average back pain on a 0-10 numerical rating scale over the past week	12 weeks
Worst leg pain	Worst leg pain on a 0-10 numerical rating scale over the past week	12 weeks
Worst back pain	Worst back pain on a 0-10 numerical rating scale over the past week	12 weeks
Oswestry Disability Index (ODI)	Oswestry Disability Index on 0-50 scale (converted to %)	12 weeks
Hospital Anxiety and Depression Scale (HADS)	Anxiety and Depression scores (0-21 for each subscale)	12 weeks
Athens Insomnia Scale	Measure of insomnia scored from 0-24	12 weeks
Analgesic medication reduction	>20% reduction in opioids or cessation of non-opioid analgesic	12 weeks
Patient global impression of change (PGIC)	Patient satisfaction with ESI on 1-7 Likert scale (1= no change, 3= a little better, 4= somewhat better 5= moderately better, 7= a great deal better)	12 weeks
Positive categorical outcome	>/=30% reduction in average leg pain (or worst leg pain if average leg pain </=4) with a PGIC >4	12 weeks
Patient satisfaction	Patient satisfaction with ESI on 1-5 Likert scale (1= very unsatisfied, 3= neutral, 5= very satisfied), recorded upon recovery area discharge	Up to 15 minutes after the procedure
Oswestry Disability Index (ODI)	Oswestry Disability Index on 0-50 scale (converted to %), with higher scores indicating greater back pain-related disability	4 weeks
Hospital Anxiety and Depression Scale (HADS)	Anxiety and Depression scores (0-21 for each subscale), with higher scores indicating greater disease burden (anxiety and depression)	4 weeks
Athens Insomnia Scale	Measure of insomnia scored from 0-24, with higher scores indicating greater sleep dysfunction	4 weeks
Leg pain at rest	Leg pain at rest on a 0-10 verbal rating scale while in the recovery area. 0=no pain, 10= worst pain imaginable.	Up to 15 minutes after the procedure
Leg pain with activity	Leg pain with walking and bending on a 0-10 verbal rating scale while in the recovery area	Up to 15 minutes after the procedure
Back pain at rest	Back pain at rest on a 0-10 verbal rating scale while in the recovery area	Up to 15 minutes after the procedure
Back pain with activity	Back pain with activity (walking, bending) on a 0-10 verbal rating scale while in the recovery area	Up to 15 minutes after the procedure

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Any adverse event or complication	10-15 minutes (for ESI)
Adverse events	Any adverse event, attributed to treatments or not	4 weeks
Adverse events	Any adverse event, attributed to treatments or not, at all time points	12 weeks

Collaborators and Investigators

• Sponsor: Northwestern University
• Collaborators: Ramathibodi Hospital; Walter Reed National Military Medical Center; Phramongkutklao College of Medicine and Hospital
• Investigators: Principal Investigator: Steven P Cohen, MD, Northwestern University Feinberg School of Medicine

Publications and helpful links

General Publications

• Kaptchuk TJ, Stason WB, Davis RB, Legedza AR, Schnyer RN, Kerr CE, Stone DA, Nam BH, Kirsch I, Goldman RH. Sham device v inert pill: randomised controlled trial of two placebo treatments. BMJ. 2006 Feb 18;332(7538):391-7. doi: 10.1136/bmj.38726.603310.55. Epub 2006 Feb 1.
• Schmidt S, Loef M, Ostermann T, Walach H. Treatment effects in pharmacological clinical randomized controlled trials are mainly due to placebo. J Clin Epidemiol. 2025 Mar;179:111658. doi: 10.1016/j.jclinepi.2024.111658. Epub 2024 Dec 27.
• Sebastian A, Wyld L, Morgan JL. Examining the variation in consent in general surgery. Ann R Coll Surg Engl. 2024 Feb;106(2):140-149. doi: 10.1308/rcsann.2023.0020. Epub 2023 May 23.
• Kern A, Kramm C, Witt CM, Barth J. The influence of personality traits on the placebo/nocebo response: A systematic review. J Psychosom Res. 2020 Jan;128:109866. doi: 10.1016/j.jpsychores.2019.109866. Epub 2019 Nov 7.
• Kang H, Miksche MS, Ellingsen DM. Association between personality traits and placebo effects: a preregistered systematic review and meta-analysis. Pain. 2023 Mar 1;164(3):494-508. doi: 10.1097/j.pain.0000000000002753. Epub 2022 Aug 10.

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2026
• Primary Completion (Estimated): March 25, 2028
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: March 23, 2026
• First Submitted That Met QC Criteria: March 23, 2026
• First Posted (Actual): March 27, 2026

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Sciatica; Back pain; Placebo effect; Lumbar radiculopathy; Epidural steroid injection; Positive framing
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia; Mononeuropathies; Sciatic Neuropathy; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Back Pain; Radiculopathy; Sciatica
• Other Study ID Numbers: STU00225684

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Military (U.S. and Thai) will require special permission to shar.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No