Clinical trial NCT06666621: Endogenous Opioid Response to Injections
Official title: Antagonism of Endogenous Opioids: Use in Interpretation of Injections
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Low Back Pain
Zygapophyseal Joint Arthritis
Keywords: low back pain
zygapophysial joint arthritis
endogenous opioids
lumbar medial branch block
Lead sponsor: Middle Tennessee Research Institute
Sponsor class: OTHER
Collaborators: name: International Pain and Spine Intervention Society
First posted: 2024-10-30
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: prospective, within-subject
Primary purpose: DIAGNOSTIC

Brief summary: This study will study pain relief after spine injections that are used to guide care. Some improvements in pain from a procedure might be from placebo effect rather than the physiological effect of the procedure. The study will use naloxone to reverse the effect of the body's internal placebo system after a spine injection, so the placebo effect and the injection effect can be measured separately. This process may improve the understanding of spine injections and their ability to guide pain care.

Detailed description: Nerve blocks are commonly used in pain medicine to diagnose painful conditions and predict response to invasive procedures and surgeries. Placebo responses may cripple clinicians' ability to interpret responses to nerve blocks and guide patient care, when reported pain relief is due to placebo rather than the nerve block.

Existing methods to assess placebo response in clinical practice are limited and indirect. The area that is most explored is in the diagnosis of pain from the facet joints of the spine and relies on an indirect signal from repeated diagnostic injections.

Lumbar medial branch radiofrequency neurotomy (LMBRN) is commonly used to treat low back pain and can lead to large improvements in pain and disability. There is a high failure rate of LMBRN even after a series of controlled prognostic injections called lumbar medial branch nerve blocks (LMBB) with local anesthetic. The discrepancy between response to LMBB and LMBRN has been attributed to the confounding of pain relief from the nerve block with pain relief from the placebo response.

Endogenous opioids (EO), substances produced within the human body that bind to opioid receptors and produce opioid analgesia, are likely responsible for most of the placebo response caused by LMBB.

This study will use naloxone, an opioid receptor antagonist, to completely block the activity of EOs in patients. First, the pain relief after LMBB will be recorded - this is a combination of the effect of the nerve block and EO released in the placebo response. Normal saline will be infused, as an internal control for the state of receiving an infusion. Naloxone will then be infused, reversing EO-dependent placebo analgesia - the analgesia remaining will be from the nerve block. Finally, clinical outcomes from LMBRN will be collected to determine whether using naloxone with LMBB can improve prediction of outcomes with LMBRN.

Naloxone will be used to probe a mechanism of procedurally-induced endogenous-opioid mediated placebo analgesia. No IND is pursued in this study.

These data will provide detailed parameters of placebo response from LMBB, improving interpretation of LMBB for estimation of prevalence of zygapophyseal joint pain and for prognostication of LMBRN.

Furthermore, if this methodology of EO reversible analgesia is feasible for investigation of placebo from LMBB, it will be more broadly investigated in diagnostic and prognostic injections used in interventional pain management.

Eligibility criteria: Inclusion Criteria:

* Capable of understanding and providing consent in English and capable of complying with the outcome instruments used
* ≥3 months low back pain with persistent limiting symptoms despite conventional treatment (physical therapy and oral medications)
* Low back pain NRS ≥ 4/10 in intensity on 7-day average and at time of lumbar medial branch block

Exclusion Criteria:

* Daily use of opioid medications or recreational drugs, or if using opioids PRN, report of opioid use within the 3 days prior to participating in the protocol
* Positive urine drug screen for opioid medication on the day of naloxone administration
* Allergy to naloxone
* Refusal of or failure to place IV
* Previous LMBB or LMBRN
* Known spine condition that may affect the ability to diagnose or treat facet pain or lead to spine surgery (e.g. instability, severe spinal stenosis, radiculopathy, previous spine operation resulting in alteration of anatomy targeted by LMBB or LMBRFN)
* Active medical condition that would limit the safety of naloxone administration (e.g. severe kidney or liver failure, unstable cardiac disease, infection, severe coagulopathy)
* Psychiatric, medical, neurologic, or pain-related disorder that may compromise the ability of the patient to accurately report changes in low back pain
* Requirement for procedural sedation to tolerate LMBB

Primary outcomes:
measure: Endogenous opioid-dependent placebo analgesia
timeFrame: 10 minutes after naloxone infusion
Secondary outcomes:
measure: Saline-reversible analgesia
timeFrame: 10 minutes after saline infusion
measure: Change in low back pain score after Lumbar Medial Branch Block #2
timeFrame: Approximately 2 weeks after Lumbar Medial Branch Block #1, and before Lumbar Medial Branch Radiofrequency Neurotomy
measure: Change in low back pain score after Lumbar Medial Branch Radiofrequency Neurotomy
timeFrame: Baseline, then 6 weeks, 3 months, 6 months after Lumbar Medial Branch Radiofrequency Neurotomy
measure: Change in McGill Pain Questionnaire-2 after Lumbar Medial Branch Radiofrequency Neurotomy
timeFrame: Baseline, then 6 weeks, 3 months, 6 months after Lumbar Medial Branch Radiofrequency Neurotomy
measure: Change in MQS-III after Lumbar Medial Branch Radiofrequency Neurotomy
timeFrame: Baseline, then 6 weeks, 3 months, 6 months after Lumbar Medial Branch Radiofrequency Neurotomy
measure: Change in Patient-Reported Outcomes Measurement Information System-29 after Lumbar Medial Branch Radiofrequency Neurotomy
timeFrame: Baseline, then 6 weeks, 3 months, 6 months after Lumbar Medial Branch Radiofrequency Neurotomy
Other outcomes:
measure: Fluoroscopy evaluation for procedural integrity - Lumbar Medial Branch Block
timeFrame: during Lumbar Medial Branch Block procedure
measure: Fluoroscopy evaluation for procedural integrity, distance - Lumbar Medial Branch Radiofrequency Neurotomy
timeFrame: during Lumbar Medial Branch Radiofrequency Neurotomy procedure
measure: Fluoroscopy evaluation for procedural integrity, displacement - Lumbar Medial Branch Radiofrequency Neurotomy
timeFrame: during Lumbar Medial Branch Radiofrequency Neurotomy procedure
Locations:
city: Nashville
country: United States
facility: VA Tennessee Valley Healthcare System
state: Tennessee
Study officials:
affiliation: Tennessee Valley Healthcare System VA
name: William E Rivers, DO
role: PRINCIPAL_INVESTIGATOR
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