Clinical trial NCT03906721: Reduction of Opioid Dose Using Conditioning & Open-Label Placebo (COLP) in Patients With Spinal Cord Injury, Polytrauma and Burn Injury
Official title: Reduction of Opioid Dose Using Conditioning & Open-Label Placebo (COLP) in Patients With Spinal Cord Injury, Polytrauma and Burn Injury: A Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Spinal Cord Injuries
Polytrauma
Burn Injury
Lead sponsor: Spaulding Rehabilitation Hospital
Sponsor class: OTHER
First posted: 2019-04-08
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a randomized single-blind open-label placebo clinical trial. 60 inpatients will be included from SRH, both men and women aged 18 or older with traumatic and non-traumatic SCI (ASIA A-D), polytrauma and burn injury patients from the Comprehensive Rehabilitation Program 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). All subjects must meet clinical criteria for the use of opioids as a treatment for pain management.
Primary purpose: TREATMENT

Brief summary: 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.

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.

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 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

Primary outcomes:
measure: Morphine Equivalent Dose Conversion (MEDC)
timeFrame: 6 days
Secondary outcomes:
measure: Modified Brief Pain Inventory (BPI)
timeFrame: Day 1 and Day 6
measure: Spinal Cord Injury - Quality of Life measurement system (SCI-QOL)
timeFrame: Day 1 and Day 6
measure: Numerical Opioid Side Effects (NOSE)
timeFrame: Day 1 and Day 6
measure: Electroencephalography
timeFrame: Day 1 and Day 6
measure: Near-infrared spectroscopy (NIRS)
timeFrame: Day 1 and Day 6
measure: Metabolomics assessment
timeFrame: Day 1 and Day 6
Other outcomes:
Locations:
city: Charlestown
country: United States
facility: Spaulding Rehabilitation Hospital
state: Massachusetts
Study officials:
affiliation: Spaulding Rehabilitation Hospital
name: Ross D Zafonte, DO
role: PRINCIPAL_INVESTIGATOR
References: