Biomarker Signatures of the Sleep-pain Enigma

Biomarker Signatures of the Sleep-pain Enigma; a Collaborative Health Initiative Research Program (CHIRP) Funded Project

This is an observational, prospective study that will leverage existing Standard of Care (SOC) patient reported outcomes (PRO) and Electronic Medical Record (EMR) data and collect additional Pain Rating Scale (PRS) data and blood samples from patients who consent to be in the study. Active duty service members and DEERS eligible patients who are injured and/or will undergo elective orthopaedic surgery are the target population.

Study Overview

• Status: Active, not recruiting
• Conditions: Post Surgical Pain and Sleep Impairment

Detailed Description

Sleep problems and pain, both acute and chronic, are common among military service members, reducing quality of life and military readiness. Evidence indicates sleep problems more strongly predict future acute and chronic pain than vice versa. This same pattern is also seen in the perioperative period, with sleep problems strongly predicting long-term post surgical pain. Though tightly linked, underlying biological mechanisms of the sleep-pain relationship in the perioperative period have yet to be identified, and treatment targets remain unknown. However, new technologies and methods in the areas of biomarker research (mRNA, microRNA, cytokine expression), as well as research describing psychosocial and clinical correlates, may help to identify patients most at-risk for long-term post-surgical sleep problems and pain, as well as identify new treatment targets.To address this research gap, the present observational study aims to collect four blood-samples from patients undergoing orthopedic surgeries at Walter Reed National Military Medical Center (WRNMMC) (N=240), both prior to and in the months following surgery, Additionally, patient reported outcomes, using the NIH's Patient Reported Outcome Measurement Information System (PROMIS), are collected as standard of care in the surgical clinics prior to surgery and for several years post-surgery. PROMIS scales cover a range of psychosocial (e.g., anxiety, depression, anger, social satisfaction, social isolation) and physical (e.g., fatigue, physical function) predictors. Through partnerships with the Defense and Veterans Center for Integrative Pain Management (USU), and WRNMMC Department of Orthopedic Surgery, the investigators will identify serum biomarkers (microRNA, cytokine expression) associated with pain and sleep-related outcomes prior to and in the months following surgery, as well as the role of psychosocial and clinical predictors, e.g. anxiety, depression, physical functioning, social functioning, opioid use) in outcomes. The long-term goal of this study are to understand risks for negative post-surgical outcomes, as well as help pave the way for future efforts to identify and test therapeutic interventions. Through this research, not only can the findings be used to improve surgical outcomes, but also increase quality of life among service members and force readiness.

• Study Type: Observational
• Enrollment (Actual): 111

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20889
      • Walter Reed National Military Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Active duty service members and DEERS eligible patients who are injured and/or will undergo elective orthopedic surgery. Up to 240 patients will be enrolled in this study at Walter Reed National Military Medical Center

Description

Inclusion Criteria:

• Active duty military or DEERS eligible individuals
• Between the ages of 18 and 60 years old
• Able to understand written and spoken English
• Eligible for healthcare within Military Health Systems
• Having an orthopedic procedure at WRNMMC

Exclusion Criteria:

• Bleeding Disorder
• History of vasovagal response

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarker Expression	To determine the biomarkers (microRNA, mRNA, proinflammatory cytokines) associated with the presence (risk-related) or absence (resilience related) of sleep dysregulation and pain prior to surgery. To determine the biomarkers associated with increases/maintenance (risk-related) and decreases (resilience-related) of sleep dysregulation and pain chronification after surgery. Protein Biomarker Analysis: The cytokine expression analysis will be done using the Human Inflammatory Cytokines Multi-Analyte ELISArray Kit. The cytokines and chemokines to be tested with this array include IL1α, IL1β, IL2, IL4, IL6, IL8, IL10, IL12, IL17A, IFNγ, TNFα, and GM-CSF (Qiagen Inc.). For this analysis, we will use 50ul of serum samples along with the 50ul of assay buffer which will be loaded in the ELISA strips.	Up to six months after surgery

Collaborators and Investigators

• Sponsor: Defense and Veterans Center for Integrative Pain Management
• Investigators: Principal Investigator: Chester C Buckenmaier, III, MD, Defense and Veterans Center for Integrative Pain Management

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2019
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: December 10, 2018
• First Submitted That Met QC Criteria: February 20, 2019
• First Posted (Actual): February 22, 2019

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 10, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative
• Other Study ID Numbers: 895846

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No