Clinical trial NCT05351333: Conditioning & Open-Label Placebo (COLP) for Opioid Management in Intensive Inpatient Rehabilitation
Official title: Conditioning & Open-Label Placebo (COLP) for Opioid Management in Intensive Inpatient Rehabilitation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Spinal Cord Injuries
Polytrauma
Burns
Keywords: open-label placebo
Spinal cord injury (SCI)
opioid
pain management
addiction prevention
pharmaco-behavioral
rehabilitation
in-patients
Lead sponsor: Spaulding Rehabilitation Hospital
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2022-04-28
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Morphine Equivalent Dose Conversion (MEDC)
timeFrame: 6 days
Secondary outcomes:
measure: Modified Brief Pain Inventory (BPI)
timeFrame: 6 days, 3 weeks, 6 weeks.
measure: Numerical Opioid Side Effects (NOSE)
timeFrame: 6 days
measure: PROMIS Pain Behavior
timeFrame: 6 days, 3 weeks, 6 weeks.
measure: PROMIS Pain Interference
timeFrame: 6 days, 3 weeks, 6 weeks.
measure: Patient Health Questionnaire 9 (PHQ-9)
timeFrame: 6 days, 3 weeks, 6 weeks.
measure: Generalized Anxiety Disorder questionnaire 7 (GAD-7)
timeFrame: 6 days, 3 weeks, 6 weeks.
measure: TEX-Q
timeFrame: 6 days
measure: TSQM-9
timeFrame: 6 days
measure: Quantitative electroencephalography (qEEG)
timeFrame: 6 days
measure: Functional near-infrared spectroscopy (fNIRS)
timeFrame: 6 days
measure: Qualitative Exit Interview
timeFrame: 1 day
measure: Metabolite assessment of 3-Methyl Xanthine
timeFrame: 6 days
measure: Metabolite assessment of Serotonin
timeFrame: 6 days
measure: Metabolite assessment of Uric acid
timeFrame: 6 days
measure: Metabolite assessment of Tyrosine
timeFrame: 6 days
measure: Metabolite assessment of Kynurenine
timeFrame: 6 days
measure: Metabolite assessment of Indole-3-Lactic acid
timeFrame: 6 days
measure: Metabolite assessment of Indole-3-Propionic acid
timeFrame: 6 days
measure: Metabolite assessment of Indole-3-Acetic acid
timeFrame: 6 days
measure: Metabolite assessment of Tryptophan
timeFrame: 6 days
measure: Metabolite assessment of Total indoxyl sulfate
timeFrame: 6 days
measure: Pain Pressure Threshold (PPT)
timeFrame: 6 days
Other outcomes:
Locations:
city: Charlestown
country: United States
facility: Spaulding Rehabilitation Hospital
state: Massachusetts
Study officials:
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