Open-label Placebo (COLP) for Pain in Adolescent Idiopathic Scoliosis (AIS) Surgery+Surgical Treatment of Idiopathic Scoliosis

Adolescent Idiopathic Scoliosis (AIS) Clinical Trial

Official title:

Effectiveness of Conditioning + Open-label Placebo for the Management of Pain in Children Who Undergo Surgical Treatment of Idiopathic Scoliosis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06365892
• Other study ID #: 22-36548
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: May 1, 2024
• Est. completion date: January 1, 2026

Study information

• Verified date: April 2024
• Source: University of California, San Francisco
• Contact: Mohammad Diab, MD
• Phone: 415-514-1519
• Email: mohammad.diab[@]ucsf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to investigate the effects of conditioning with open-label placebos on standard postoperative treatment for patients undergoing surgery for idiopathic scoliosis in a randomized controlled, 6-week trial with 64 AIS patients randomly assigned to one of two arms: Open-label Placebo (COLP) + treatment as usual TAU / TAU control. The study involves collecting data from your child's medical record. At each regular clinic visit, the patient clinical data will be collected by the research coordinator. Surveys will be collected including:• PROMIS for the age group 10 to 18 years.

Description:

Interventional (clinical trial): Subject will be randomly assigned using permuted blocks (block size of 4). Before usage, random assignments will be created, stored in sealed envelopes, and numbered (1, 2, etc.). There will be stratified randomization: Later on, stratification will be incorporated into the analysis. 32 people will be in the group taking the placebo pills in addition to standardized treatment and 32 people will be in the group with standardized treatment alone.

Hypothesis: Open-label Placebo (COLP) < treatment as usual (TAU) control. Secondary Aims Analysis Plan: There are three secondary aims in this study.

Aim 1. To determine whether 6 weeks of Open-label Placebo (COLP) results in significantly reduced opioid consumption compared to treatment as usual. To test this aim, the investigators will conduct a t-test comparing mean opioid use over the 6 weeks of follow up. In secondary analyses, the investigators will adjust for any baseline factors including gender, age, symptom severity or type of surgery that could be a confounding variable.

1a. To determine if 6 weeks of Open-label Placebo (COLP) results in reduced opioid consumption compared to treatment as usual. Hypothesis: Open-label Placebo (COLP) < treatment as usual (TAU) control.

Secondary Aims Analysis Plan: There are three secondary aims in this study.

Secondary Aim 1: Determine if there are significant differences in time to independence with physical therapy, length of stay, time to return to school, urinary retention, constipation, oxygen requirement, and number of contacts with medical team in Open-label Placebo (COLP) compared to treatment as usual (TAU).

Secondary Aim 2: Determine if there is an association between preoperative pain catastrophization, kinesiophobia, positive/negative affect, anxiety, and/or depression and response to Open-label Placebo (COLP) and/or treatment as usual (TAU).

Secondary Aim 3: Determine if there is an association between postoperative PROMIS scores, anxiety, and/or depression in open-label placebo (COLP) compared to treatment as usual (TAU).

Primary Objectives The primary objectives of this study are to: (1) to determine whether 6 weeks of conditioning with open-label placebo (COLP) results in reduced opioid consumption (amount and duration) compared to treatment as usual (TAU) control and (2) to determine whether 6 weeks of Open-label Placebo (COLP) compared to treatment as usual (TAU) results in different clinical outcomes.

Secondary Objectives

• To determine whether open-label placebo (COLP) affects anxiety and/or depression.

• To determine whether open-label placebo (COLP) affects length of stay, opioid side effects, time to independence with physical therapy, and/or number of contacts with medical team.

• To determine if there is an association between pain catastrophizing, kinesiophobia, and clinical outcomes.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 64
• Est. completion date: January 1, 2026
• Est. primary completion date: January 1, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 10 Years to 18 Years

Eligibility

Inclusion Criteria:

To be eligible for enrollment, patients must meet all of the following inclusion criteria:

1. Diagnosis of idiopathic spine deformity.

2. Age >10 and <18 years.

3. Primary procedure.

4. Guardian provides signed and dated informed consent and understand the nature of the study sufficiently to allow completion of all study assessments.

5. Patient provides assent.

6. Fusion and fusionless instrumented spine surgery.

Exclusion Criteria:

If any of the following exclusion criteria are met, the patient is not eligible for the study:

1. Non-idiopathic scoliosis, such as neuromuscular or syndrome.

2. Revision procedure.

3. Self-reported pregnancy or planned pregnancy within the next two months.

4. Have a history of drug, excluding nicotine or caffeine, or alcohol abuse within 2 years of entry into the study

5. Already taking opioids.

6. Abnormal physical examination.

7. Inability to speak or read English

8. Patient declines participation.

Related Conditions & MeSH terms

• Adolescent Idiopathic Scoliosis (AIS)
• Scoliosis

Intervention

Drug:
• open-label placebo
Placebo will be supplied as a 330mg tablet (manufactured by Consolidated Midland Corporation). Patients will take placebo with each oral opioid intake and 3 additional times per day beginning on POD 1.

Other:
• Treatment as usual
Each oral opioid dose is a 5mg Oxycodone tablet. Investigator shall never prescribe ibuprofen. Investigator shall always prescribe Tylenol 625mg every 8hrs (PRN).

Locations

Country	Name	City	State
United States	University of California, San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Francisco

Country where clinical trial is conducted

United States, 

References & Publications (10)

Allahabadi S, Wu HH, Allahabadi S, Woolridge T, Kohn MA, Diab M. Concurrent and overlapping surgery: perspectives from surgeons on spinal posterior instrumented fusion for adolescent idiopathic scoliosis. J Child Orthop. 2021 Dec 1;15(6):589-595. doi: 10.1302/1863-2548.15.210142. — View Citation

Hung NJ, Theologis AA, Courtier JL, Harmon D, Diab M. Ureteral injury following anterior thoracolumbar spinal instrumented fusion for adolescent idiopathic scoliosis: a case report with CT angiography analysis of surgically relevant anatomy. Spine Deform. 2021 Nov;9(6):1691-1698. doi: 10.1007/s43390-021-00363-x. Epub 2021 Jun 1. — View Citation

Iriondo C, Mehany S, Shah R, Bharadwaj U, Bahroos E, Chin C, Diab M, Pedoia V, Majumdar S. Institution-wide shape analysis of 3D spinal curvature and global alignment parameters. J Orthop Res. 2022 Aug;40(8):1896-1908. doi: 10.1002/jor.25213. Epub 2021 Nov 29. — View Citation

O'Donnell JM, Gornitzky AL, Wu HH, Furie KS, Diab M. Anterior vertebral body tethering for adolescent idiopathic scoliosis associated with less early post-operative pain and shorter recovery compared with fusion. Spine Deform. 2023 Jul;11(4):919-925. doi: 10.1007/s43390-023-00661-6. Epub 2023 Feb 21. — View Citation

Oeding JF, Siu J, O'Donnell J, Wu HH, Allahabadi S, Saggi S, Flores M, Brown K, Baldwin A, Diab M. Combined Anterior Thoracic Vertebral Body Tethering and Posterior Lumbar Tethering Results in Quicker Return to Sport and Activity Compared to Posterior Spinal Instrumented Fusion in Patients with Adolescent Idiopathic Scoliosis. Global Spine J. 2023 Dec 14:21925682231222887. doi: 10.1177/21925682231222887. Online ahead of print. — View Citation

Siu JW, Wu HH, Saggi S, Allahabadi S, Katyal T, Diab M. Perioperative Outcomes of Open Anterior Vertebral Body Tethering and Instrumented Posterior Spinal Fusion for Skeletally Immature Patients With Idiopathic Scoliosis. J Pediatr Orthop. 2023 Mar 1;43(3):143-150. doi: 10.1097/BPO.0000000000002320. Epub 2022 Dec 6. — View Citation

Siu JW, Wu HH, Saggi S, Allahabadi S, Katyal T, Diab M. Radiographic and perioperative outcomes following anterior thoracic vertebral body tethering and posterior lumbar spine tethering: a pilot series. Spine Deform. 2023 Nov;11(6):1399-1408. doi: 10.1007/s43390-023-00717-7. Epub 2023 Jun 25. — View Citation

Theologis AA, Wu HH, Diab M. Thoracic posterior spinal instrumented fusion vs. thoracic anterior spinal tethering for adolescent idiopathic scoliosis with a minimum of 2-year follow-up: a cost comparison of index and revision operations. Spine Deform. 2023 Mar;11(2):359-366. doi: 10.1007/s43390-022-00586-6. Epub 2022 Sep 21. — View Citation

Theologis AA, Wu HH, Oeding JF, Diab M. Costs of revision operations for distal junctional kyphosis following thoracic posterior spinal fusion for adolescent idiopathic scoliosis. Eur Spine J. 2024 Feb 20. doi: 10.1007/s00586-024-08160-6. Online ahead of print. Erratum In: Eur Spine J. 2024 Apr 10;: — View Citation

Zaid M, Diab M. Surgeon Suicide Remains a Critical Issue for the Orthopaedic Profession. J Bone Joint Surg Am. 2021 Oct 20;103(20):e81. doi: 10.2106/JBJS.20.01125. No abstract available. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The total amount of opioids consumed in oral morphine equivalents (OMEs) following surgery	Oral morphine equivalents (OMEs) are values that represent the potency of an opioid dose relative to morphine. Using OMEs provides a standardized method for converting between various opiate medications. Each oral opioid dose is a 5mg Oxycodone tablet prescribed 6 times per day pro re nata. Participants will record the number of oral opioids taken each day for 6 weeks following surgery beginning on Post-op Day 1 (POD1). This data will be collected and converted into OMEs for comparison.	from admission to 6 weeks post-operatively
Secondary	Weekly level of mobility and change from baseline in mobility on the Patient-Reported Outcome Measurement Information System (PROMIS) Numeric Rating Scale Pediatric Mobility Short Form 7a at week 6.	the PROMIS Pediatric Mobility SF 7a is a validated, self-reported instrument that consists of 7 items rating mobility on average over the past 7 days from 4 (With no trouble) to 0 (not able to do). Weekly level of mobility = mobility score reported at each week Change = (Week 6 Score - Baseline Score).	weekly from admission to 6 weeks post-operatively
Secondary	Weekly level of anxiety and change from baseline in anxiety levels on the Patient-Reported Outcome Measurement Information System (PROMIS) Numeric Rating Scale Anxiety Short Form 8a at week 6.	the PROMIS Anxiety SF 8a is a validated, self-reported instrument that consists of 8 items rating anxiety on average over the past 7 days from 1 (never) to 5 (almost always). Weekly level of anxiety = anxiety score reported at each week Change = (Week 6 Score - Baseline Score).	weekly from admission to 6 weeks post-operatively
Secondary	Weekly level of depressive symptoms and change from baseline in depressive symptoms on the Patient-Reported Outcome Measurement Information System (PROMIS) Numeric Rating Scale Depressive Symptoms Short Form 8a at week 6.	the PROMIS Depressive Symptoms SF 8a is a validated, self-reported instrument that consists of 8 items rating depressive symptoms on average over the past 7 days from 1 (never) to 5 (almost always).; Weekly level of depressive symptoms = depressive symptoms score reported at each week Change = (Week 6 Score - Baseline Score).	weekly from admission to 6 weeks post-operatively
Secondary	The duration of time in days following surgery until patients establish Independence with Physical Therapy	Participants will be treated by physical therapy services after surgery until their physical therapist determines that they no longer require physical therapy services. Duration of time to independence with physical therapy is equal to the POD # where physical therapist determines formal PT is no longer required.	from admission to final physical therapy assessment, up to 6 weeks
Secondary	The length of time in days following surgery until discharge from the hospital	Participants will be admitted to the hospital following surgery until they are cleared for discharge from a medical standpoint.; Length of stay = POD # that patient is discharged	from admission to discharge, up to 6 weeks
Secondary	The length of time in days following surgery until participant returns to school	Participants will record the date on which they return to school after surgery. The POD # on date of return to school = the length of time to return to school. The amount of time it takes to return to school can be used as a proxy for whether participants are struggling with their pain or not.	from admission to date of return to school, up to 6 weeks post-operatively
Secondary	Whether participants experience urinary retention following surgery.	Participants will be assessed in hospital to determine whether or not they experience urinary retention post-surgery, a potential side effect of opioid consumption. The urinary retention determination will be a yes/no answer.	during hospitalization until discharge, up to 6 weeks
Secondary	Whether participants experience constipation measured by the number of days between surgery and first bowel movement	Participants will record the number of days between surgery and first bowel movement to assess whether they experience constipation, a potential side effect of opioid consumption.	from admission to date of first bowel movement, up to 6 weeks post-operatively
Secondary	Whether participants experience an oxygen requirement and the duration of the requirement following surgery.	Participants will be assessed in hospital for whether or not they have an oxygen requirement and the duration of requirement. The oxygen requirement will be a yes/no answer. If yes, the number of days that oxygen is required will be recorded for the duration.	during hospitalization until discharge, up to 6 weeks

External Links

•   Mohammad Diab, MD