Conditioning & Open-Label Placebo (COLP) for Opioid Management in Intensive Inpatient Rehabilitation

NCT ID: NCT05351333

Last Updated: 2025-10-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

66 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-08-03

Study Completion Date

2026-07-31

Brief Summary

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The use of the conditioning open-label placebo (COLP) paradigm 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 intake to diminish side effects as well as the risk of addiction associated with opioid treatment.

Detailed Description

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The study is a randomized controlled trial (RCT) parallel-group, assessor blind with one experimental arm, the conditioning open-label placebo (COLP), and one control group following the regular regimen, treatment as usual (TAU).

Tools for assessment: Morphine Equivalent Dose Conversion (MEDC); Pain Pressure Threshold (PPT); Modified Brief Pain Inventory (BPI); PROMIS Pain-Related Measures (PROMIS); Numerical Opioid Side Effects (NOSE); Treatment satisfaction questionnaire for medication (TSQM) and Treatment expectation questionnaire (TEX-Q); Measurements of anxiety, depression - Generalized Anxiety Disorder 7 (GAD7) and Patient Health Questionnaire-9 (PHQ9). Recording of medication changes and side effects. Reported visual analog scale (VAS) for pain assessed by the nursing team and recorded at the electronic medical record (EMR); finally, the qualitative exit interview.

Neurophysiological and metabolomic phenotyping, using the following measures, Quantitative electroencephalography (qEEG) for quantitative assessment (EEG), functional near-infrared spectroscopy (fNIRS), and metabolomics assessment.

Following enrollment, subjects will be randomized to receive COLP treatment or a standard of care opioid dosage. The study team will perform baseline assessments, and subjects in the COLP group will undergo three consecutive days of prescribed - as needed - pro re nata (PRN) opioid 100% dose + opioid conditioning paired with taste and odorous placebos (pill and smell).

Afterward, subjects will receive a 50% dose + COLP for three days. The nursing team will alternate the active opioid medication with total placebo dosages to decrease the therapeutic opioid dose by 50%.

Voluntary COLP continuation: After the participants have completed the experimental intervention (day 6), all outcomes have been collected (pre and post-measurements). Patients randomized to the COLP group will be asked to continue the COLP intervention during hospitalization if the participant agrees to continue using COLP. We will re-evaluate the following variables: MEDC, PPT, BPI, PROMIS pain, TSQM, and NOSE once COLP is discontinued (e.g., in case of increased pain and opioid utilization or if the patient is being discharged and transferred to another facility).

For subjects allocated in the control group (treatment-as-usual), the customary treatment routine will follow the standard of care for patients suffering from mild to moderate pain, including all pharmacological agents (NSAIDs, narcotics, and combos) used for pain management. The study team will record total narcotic dosages at the beginning and end of the trial.

Conditions

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Spinal Cord Injuries Polytrauma Burns

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Conditioning Open-Label Placebo

Days 1 to 3 will include the acquisition phase where the opioid medication will be prescribed on a schedule of 3-4 times per day and paired with an open-label placebo. Day 4 and 6 will be the evoked phase, and patients will receive only the open-label placebo pill. On day 5 the opioid medication will be re-introduced as pharmacological reinforcement.

Group Type EXPERIMENTAL

placebo

Intervention Type OTHER

Sugar pill, with an essential-oil smell and of blue color used for conditioning.

Treatment as usual

Patients in the standard of care group will receive their analgesic treatment through Spaulding Pharmacy as prescribed by their treating physicians. The treatment regime will include an opioid medication at the standard recommended dosage. Participants in this group will receive the treatment orally for 6 consecutive days.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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placebo

Sugar pill, with an essential-oil smell and of blue color used for conditioning.

Intervention Type OTHER

Other Intervention Names

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open-label placebo

Eligibility Criteria

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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 than five 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 nociceptive pain (musculoskeletal or visceral) that is moderate or severe (average VAS scale score of 4 or greater at time of enrollment),
* Inpatients with polytrauma (defined as having injuries that affect two or more body systems or organs) or patients with burn injuries, amputations, or post-surgical (e.g., orthopedic surgery)
* 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,
* 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 a dosage higher than 120 mg of morphine equivalent or 80 mg of short-acting oxycodone, or 30 mg of hydromorphone
* Current use of a ventilator,
* Compromised medical status due to uncontrolled pathologies such as cancer, heart failure, kidney or liver insufficiency, or any other condition which jeopardizes the patient's participation in the study
* Pregnancy or breastfeeding. Participants with pregnancy capability will be tested for pregnancy by serum human chorionic gonadotropin (hCG) test.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role collaborator

Spaulding Rehabilitation Hospital

OTHER

Sponsor Role lead

Responsible Party

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Jorge Leon Morales-Quezada, MD, PhD

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Spaulding Rehabilitation Hospital

Charlestown, Massachusetts, United States

Site Status

Countries

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United States

References

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Other Identifiers

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1K23DA052041-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2022P000486

Identifier Type: -

Identifier Source: org_study_id

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