Clinical trial NCT06639438: Sensory Outcomes in Active Substance Users
Official title: Molecular and Behavioral Characterization of Post-Operative Sensory Outcomes in Individuals With Chronic Pain or Persistent Opioid Use
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Post Operative Pain
Opioid Use, Unspecified
Keywords: Opioid use disorder (OUD)
Gene expression
Visium slide sequencing
Inflammatory profile
Sensation pain
Flow cytometry
Lead sponsor: Boston Medical Center
Sponsor class: OTHER
First posted: 2024-10-15
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects with elective spine procedures scheduled involving incision (including laminectomy, discectomy, foraminotomy, scoliosis correction, decompression and fusion) will be divided into four groups: two no opiod use groups and two opioid use groups. The no opioid use groups will consist of two subgroups of participants with no prior pain disorders who have received no long-term opioid prescriptions (n=10), as well as patients with chronic pain disorders who have received no long-term high dose opioid prescriptions (n=10). The opioid use group will consist of two subgroups- participants with OUD (n=10), and participants without OUD, but have been prescribed opioid medication for chronic pain disorders (n=10).

Brief summary: The incidence and severity of postoperative pain after spine surgery are notably high, often requiring intensive management and potentially affecting the patient's recovery, satisfaction, and long-term outcomes. Post-operative pain is particularly difficult to manage in patients with substance use disorder likely due to a combination of withdrawal symptoms and molecular changes in the pain matrix. Opiates are the leading cause of overdose related fatalities, and carry a significant burden of substance related morbidity and mortality. As over 80% of patients undergoing low-risk surgery receive opioid prescriptions, the investigators aim to identify unique molecular characteristics of pain within current and previous opioid users, which have been understudied in this context. This study also seeks to understand the molecular mechanisms underlying worsened postoperative pain in patients with opioid use disorder (OUD).

Flow cytometry analysis of human serum will be done, which will assess circulating immune cells that can contribute to exacerbated surgery site inflammation. Spatial profiling of gene expression will be done in the dermis using Visium slide sequencing, focusing on the interplay between nerve endings, resident immune cells, and supporting dermal cells, all of which collectively contribute to the sensation pain. Both the visual pain rating scale and McGill Pain Questionnaire will be used to comprehensively quantify pain outcomes during the participant's postoperative recovery stay after surgery in an effort to better understand postoperative pain management with biomarkers of worsened postoperative pain.

Detailed description: The objective for this research are:

1. Assess differences in pain reception in patients with existing or previous opioid use disorder versus controls after elective spine surgery via pain questionnaires at multiple time points during the perioperative care.
2. Assess circulating immune signatures and neuropeptides associated with pain signaling before and after surgery in patients with and without OUD using flow cytometry and ELISA of patient serum.
3. Assess molecular signatures of dermal cells and nerve endings patients with and without OUD using spatial transcriptomics on epidermis- and dermis-containing tissue samples from surgical incision.

Eligibility criteria: Inclusion Criteria:

Opioid user cohorts:

* Individuals with current OUD as defined by The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)
* Individuals requiring ≥20 mg of MME/day medication to manage a chronic pain problem.
* Patients scheduled to undergo elective surgery
* Able to provide informed consent

Control Group Cohorts:

* Individuals who are not taking high dose opioids (≤20 MME/day) nor illicit substances and have no history of opioid use disorder
* Individuals with reported chronic pain not yet taking medication for their pain
* Patients scheduled to undergo elective surgery
* Able to provide informed consent

Exclusion Criteria:

Substance User Cohort:

* Patients with contraindications for elective surgery
* Individuals with no history of opioid use

Control Group Cohort:

* Individuals with a history of opioid use \>20 MME/day or illicit substance use
* Patients with contraindications for elective surgery.

Primary outcomes:
measure: Specific gene expressed
timeFrame: The date of scheduled surgery assessed through the study completion, about two years
measure: Type and concentration of inflammatory cells present and selective biomarkers
timeFrame: The date of scheduled surgery assessed through the study completion, about two years
Secondary outcomes:
measure: Perceived pain using a visual pain scale
timeFrame: ~2 weeks before surgery; 24, 36, 48, and 72 hours post-surgery before discharge; ~2 weeks after discharge
measure: Perceived pain using the McGill pain scale
timeFrame: ~2 weeks before surgery; 24 hours post-surgery before discharge; ~2 weeks after discharge
measure: Anesthesia and pain management method
timeFrame: Within 1 week of the surgical visit
measure: Opioid burden
timeFrame: Within 1 week of the surgical visit
measure: Post-operative recovery and complications
timeFrame: Within 1 week of the surgical visit
measure: Perceived pain during postsurgical recovery using the remote pain survey.
timeFrame: 1, 2, 3, 4 week post-discharge
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Medical Center/Boston University Medical Campus
state: Massachusetts
Study officials:
affiliation: Boston Medical Center, Anesthesiology
name: Ala Nozari, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: