Reduction of Opioid Dose Using Conditioning & Open-Label Placebo (COLP) in Intensive Rehabilitation (COLP)

Reduction of Opioid Dose Using Conditioning & Open-Label Placebo (COLP) in Patients With Spinal Cord Injury, Polytrauma and Burn Injury: A Pilot Study

The use of conditioning open-label placebo (COLP) will be studied as a dose extension method to lower opioid dosage in patients with spinal cord injury, polytrauma, and burn injury. The goal is to provide the same level of pain relief with a reduced opioid dose to diminish adverse effects as well as the risk of addiction associated with narcotic treatment.

Study Overview

• Status: Completed
• Conditions: Pain Management; Spinal Cord Injuries; Burn Injury; Polytrauma
• Intervention / Treatment: Drug: Placebo; Drug: Oxycodone; Other: Essential Oil

Detailed Description

The investigators will conduct an assessor blind controlled clinical trial, participants in the COLP group will be fully informed about the interventions the participants will be allocated for. As this study is designed to be a proof-of-concept, only an authorized member of the study staff will be conducting the assessments. Suppose the subject has been approved to participate by the treating physician. In that case, the co-investigator will discuss the study's details and answer questions both before and during the first study visit.

Study Design and Flow:

This study contains one experimental arm and one control group. The experiment will run in a parallel design, with each subject having six days of participation. Each group will have evaluations before starting the trial (Baseline) and assessments after the six days of study participation. Subjects will be evaluated using the following tools: Morphine Equivalent Dose Conversion (MEDC); Modified Brief Pain Inventory (BPI); Spinal Cord Injury - Quality of Life measurement system (SCI-QOL); and Numerical Opioid Side Effects (NOSE). The investigators will also record medication changes, side effects, and pain levels as measured by the Visual Analog Scale (VAS) daily for each patient.

For this open placebo- opioid dose reduction study. The investigators will enroll a total of 60 subjects with SCI, polytrauma, and burn injury patients from the Comprehensive Rehabilitation Program at Spaulding Rehabilitation Hospital and ongoing neuropathic or nociceptive pain. Experimental treatments will take place at either Spaulding Rehabilitation Hospital (SRH). The investigators will coordinate with the appropriate care outlets to ensure that the study's procedures will not interfere with their standard of care at Spaulding. This includes, but is not limited to: physicians, therapists, and nurses working with the patient. The investigators will schedule inpatients as their clinical schedule allows.

After enrollment, subjects will be randomized to receive COLP treatment or to receive standardized opioid dosage.

Oxycodone Intervention and Rescue Medication:

All patients enrolled in this study will receive oxycodone as primary opioid medication for pain control. The treating physician will prescribe a short-acting form of oxycodone 3-4 times per day. The accepted range dosage for this medication will be from 10 to 50 mg PO per day (Q24H), treating physicians will decide the oxycodone dosage to control pain effectively. The investigators expect patients enrolled in this study to take an average of 30-40 mg of oxycodone per day (Q24H).

If a subject requires rescue medication, it will be determined by clinical staff.

Baseline assessments will be performed by the investigators. Subjects on the COLP group will undergo three consecutive days of opioid conditioning paired with taste and odorous placebos (pill and smell), followed by three days of the evoked response phase, where the active opioid medication will be alternated with full placebo dosages to decrease the therapeutic opioid dose by 50%. Females of childbearing age-eligible to participate in the study will be tested for pregnancy using a serum human chorionic gonadotropin (hCG) test.

The treatment regime and schedule for patients in the COLP group will include a short-acting opioid prescribed on a program of 3-4 times per day. This will be considered the active agent for the pharmaco-conditioning intervention; subjects will have access and receive rescue medication if necessary (PRN). Other forms of analgesics (NSAIDs and combos) will be prescribed under the criteria of treating physicians; if combined agents containing opiates are used, a morphine equivalence calculation will be applied.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Charlestown, Massachusetts, United States, 02129
      • Spaulding Rehabilitation Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men and women aged 18 or older with traumatic and non-traumatic SCI (ASIA A-D) polytrauma or burn injury patients from the Comprehensive Rehabilitation Program at Spaulding Rehabilitation Hospital,
• SCI, polytrauma or burn injury patients from the Comprehensive Rehabilitation Program at Spaulding Rehabilitation Hospital and pain of no more 5 years of evolution,
• Patients admitted to the Spaulding Comprehensive Rehabilitation Unit at Spaulding Rehabilitation Hospital,
• Who have; above, at, or sub-lesional neuropathic pain and/or nociceptive pain (musculoskeletal or visceral) that is moderate or severe in nature (average VAS scale score of 4 or greater at time of enrollment),
• Respiratory and hemodynamically stable,
• With current narcotic use for pain control,
• Narcotic usage of no more than 120 mg of morphine equivalent

Exclusion Criteria:

• History of alcohol or drug dependence, as self-reported,
• A history of bipolar disorder or psychosis, as self-reported,
• Any substantial decrease in alertness, language reception, or attention that might interfere with understanding,
• Current usage of narcotic medication with dosage higher than 120 mg of morphine equivalent or 80 mg of a short-acting oxycodone,
• Current use of ventilator,
• Compromised medical status due to uncontrolled pathology such as cancer, heart failure, kidney or liver insufficiency, or any other condition which jeopardises patient's participation to the study
• Pregnancy or breastfeeding. Females in childbearing age who are eligible to participate in the study, will be tested for pregnancy by serum hCG test

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Conditioning & Open-Label Placebo (COLP); Days 1 to 3 will include the acquisition phase where oxycodone will be prescribed on a schedule of 3-4 times per day and paired with open-placebo and smelling the essential oil. Days 4 to 6 will be the evoked phase, and patients will receive full oxycodone dosage on alternating days with open placebo and smelling the essential oil.	Drug: Placebo; Sugar pill used to condition patients.; Drug: Oxycodone; An opioid used for analgesia.; Other Names: Oxycodone Hydrochloride Tablets; Other: Essential Oil; An aromatic oil used for conditioning.
Other: Treatment-as-usual; For the duration of the study, days 1 to 6, oxycodone will be prescribed on a schedule of 3-4 times per day.	Drug: Oxycodone; An opioid used for analgesia.; Other Names: Oxycodone Hydrochloride Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morphine Milligram Equivalents (MME)	Morphine Milligram Equivalents (MME) are used to standardize opioid exposure by expressing the analgesic potency of different opioids relative to morphine. MME is calculated by multiplying the prescribed opioid dose by the daily frequency of administration and then by an opioid-specific conversion factor. The resulting value is expressed as milligrams of morphine equivalents (mg MME). Values range from 0 mg MME upward, with higher values indicating greater opioid exposure, which has been associated with an increased risk of adverse clinical outcomes.	6 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Analog Scale for Pain (VAS)	The Visual Analog Scale (VAS) is a measurement tool used to quantify pain intensity. It consists of a 10-point anchored by a minimum value of 0, representing "no pain," and a maximum value of 10, representing the "worst pain imaginable." Patients mark their perceived pain level; higher scores indicate a worse outcome, reflecting greater pain severity or distress. For this outcome, we are reporting the difference in VAS from Day 1 to Day 6.	Day 6
Spinal Cord Injury - Quality of Life Measurement System (SCI-QOL)	This measurement system was developed to address the shortage of relevant and psychometrically sound patient reported outcome measures available for clinical care and research in spinal cord injury (SCI) rehabilitation. For the purpose of this research, the Pain Behavior subdomain will be the primary component of this scale to be used. This 7-item fixed-length scale measures manifestations of pain. These actions or reactions can be verbal or non-verbal and involuntary or deliberate. They include observable displays, and verbal reports of pain. This scale includes a small subset of the Patient-Reported Outcomes Measurement Information System (PROMIS ) Pain Behavior item bank (i = 4) and three new items.	Day 1 and Day 6
Numerical Opioid Side Effects (NOSE)	The Numerical Opioid Side Effect (NOSE) assessment tool is a simple, rapid, self-administered instrument to document and longitudinally follow trends of opioid adverse effects. The NOSE typically assesses 10 common, specific opioid side effects, including nausea, fatigue/drowsiness, constipation, itching, decreased libido, dry mouth, abdominal pain, sweating, dizziness, and urinary retention, with each item rated on this 0-10 scale. Higher values on the NOSE scale represent worst side effects Minimum Score: 0 (indicates no problems with opioid side-effects) Maximum Score: 100 (indicates the worst possible opioids side-effects) The reported outcome is the change in NOSE from Day 1(baseline) to Day 6(post-intervention)	Change in NOSE score from Day 1 and Day 6
Electroencephalography - Power Spectrum	Electroencephalography (EEG) is an electrophysiological monitoring method to record the electrical activity of the brain. Quantitative electroencephalography (qEEG) stands out as a valuable, non-invasive tool because it provides reliable and relevant information about brain functioning during rest, sensory stimulation, and cognitive tasks. Besides, this technique is safe, low-cost, and employs a straightforward methodology, making it an appropriate tool for clinical practice. The EEG recordings will be processed for analytical purposes by the investigators will explore standard EEG metrics (e.g., spectral analysis).	Power spectrum Change from Day 1 to Day 6
Near-infrared Spectroscopy (NIRS)	NIRS is a spectroscopic method that uses the near-infrared region of the electromagnetic spectrum. This method is based on near-infrared light absorption fluctuations that depend on concentration changes of the chromophores oxygenated hemoglobin (O2Hb) and deoxygenated hemoglobin (HHb). The values are usually expressed in micromolar units (mM) of concentration change relative to a baseline. The higher the O2Hb value, represents higher cortical activity. Higher HHb represents decreased cortical activity. The outcome is reported as the change O2Hb and HHb from Day 1(baseline) to Day 6 (post-intervention)	Day 1 and Day 6
Metabolomics Assessment	Metabolomics is the large-scale study of small molecules. The analysis will focus on pathways associated with cognitive and cellular metabolism. The investigators will collect samples by pinprick system, and analysis will be done using liquid chromatography (LC) technique and by employing Electrochemical Array Detection (ECA). Concentration of metabolites will be reported and used for analysis using the absolute quantification value in (micromolar). This outcome measure data represents the change in metabolite concentration from baseline to post-intervention.	Day 1 and Day 6. This outcome measure data represents the change in metabolite concentration from Day 1 (baseline) to Day 6(post-intervention)

Collaborators and Investigators

• Sponsor: Spaulding Rehabilitation Hospital
• Investigators: Principal Investigator: Ross D Zafonte, DO, Spaulding Rehabilitation Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2019
• Primary Completion (Actual): November 1, 2021
• Study Completion (Actual): November 1, 2021

Study Registration Dates

• First Submitted: April 4, 2019
• First Submitted That Met QC Criteria: April 4, 2019
• First Posted (Actual): April 8, 2019

Study Record Updates

• Last Update Posted (Actual): August 4, 2026
• Last Update Submitted That Met QC Criteria: July 9, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Opioids; Conditioning; Open-label placebo
• Additional Relevant MeSH Terms: Neurologic Manifestations; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Neurobehavioral Manifestations; Trauma, Nervous System; Spinal Cord Diseases; Perceptual Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Multiple Trauma; Spinal Cord Injuries; Burns; Agnosia; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Lipids; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Morphine Derivatives; Oils; Codeine; Oxycodone; Oils, Volatile
• Other Study ID Numbers: 2017P001673

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No