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Completed

NCT Number: NCT04271072

CSF/Serum Biomarkers in Predicting PND/Persistent Pain After Cesarean

The aim is to investigate if inflammatory biomarkers in the blood and cerebrospinal fluid (CSF) are associated with the development of perinatal depression and/or persistent pain after cesarean delivery.

This study will obtain CSF and blood samples in 70 parturients. All parturients will be assessed for perinatal depression and persistent pain, and the presence/absence of these outcomes will be correlated to changes in the inflammatory biomarkers within the samples collected. If present, consistent changes in biomarkers correlating with perinatal depression or persistent pain may be utilised as a predictive tool and facilitate early treatment for these conditions.

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Key information

Conditions

Perinatal Depression Chronic Pain Inflammation Nervous System Diseases Neuroinflammatory Diseases Neurologic Manifestations Pain Pathologic Processes Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year–40 year

Sex eligibility

Female

Study type

Observational

Primary location

Duke University Medical Center

Durham, North Carolina, 27710, United States

About this study

Persistent pain and perinatal depression (PND) contribute significantly to maternal morbidity and mortality after cesarean delivery. Neuroinflammation has been associated with both persistent pain and perinatal depression, and may therefore be a common etiological process, however, little is known of the association between neuroinflammation and persistent pain or PND in parturients undergoing cesarean delivery.

Aim 1: To compare neuroinflammatory cytokine profiles (in CSF and plasma samples within 48 hours after surgery) between the cohort of parturients that develop the composite outcome of persistent pain or PND (defined below), versus the cohort of parturients that did not develop this outcome.

Aim 2. To determine the correlation between the neuroinflammatory cytokine profiles of CSF and plasma.

Exploratory aim: To determine the change in plasma inflammatory cytokine profile from the antenatal to the postnatal period, and correlate this change with preoperative quantitative sensory tests, acute postsurgical pain severity, and development of persistent pain and/or PND. To examine proteomics in CSF and correlate with persistent pain and/or PND.

This is a prospective cohort study of 70 adult parturients undergoing elective cesarean delivery at Duke University Hospital. After obtaining informed consent, baseline demographic data, the Edinburgh Postnatal Depression Scale (EPDS), mechanical temporal summation (MTS), and pain-pressure threshold (PPT) tests will be administered. During IV cannulation, 10ml of blood will be collected, and up to 10ml CSF will be collected during spinal anesthesia. After cesarean delivery, pain scores, analgesia requirements, and data on adverse events will be collected. Additional 10ml of blood will be collected within 48 hours post-surgery during inpatient hospital stay. During the routine 6-week postnatal follow up, EPDS scores will be recorded, and at 3-months, EPDS and persistent pain assessment will be conducted over the phone.

Based on a composite endpoint of persistent pain (pain at 3 months after surgery) or PND (EPDS of 10 or greater, during pregnancy or within 3 months after delivery), parturients will be stratified into "study" or "control" cohorts. Using a validated multiplex quantitative proteomic approach, candidate biomarkers will be quantified and correlated against the composite outcome using two-sided Mann-Whitney U test. Correlation between CSF and plasma cytokines will be assessed using spearman correlation. The exploratory aim will be analyzed with generalized linear models.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • American Society of Anesthesiologists (ASA) class 2 and 3
  • English speaking
  • 18 years or older
  • Singleton pregnancy
  • Gestational age > 37 weeks
  • Scheduled cesarean delivery under spinal or combined spinal epidural anesthesia

Exclusion criteria

  • Intravenous drug or chronic opioid use
  • Anti-depressant or anxiolytic drug use
  • Allergy to standard of care drugs
  • Cesarean delivery under general anesthesia or epidural anesthesia
  • Pre-eclampsia needing magnesium sulfate
  • Chronic PO/IV analgesic or glucocorticoids
  • History of chronic pain syndromes

Treatment and study plan

No intervention

Other

No intervention

Primary outcomes

  1. Perinatal depression

    Time frame: Up to 3 months after delivery

    Edinburgh postnatal depression scale >=10 (minimum 0, maximum 30, increasing score indicates higher likelihood of depression)

  2. Persistent pain: Pain score

    Time frame: Up to 3 months after delivery

    Pain score >=3 at pelvic or lower abdominal areas (minimum 0, maximum 10, higher score indicates greater pain)

  3. Inflammatory cytokines/biomarkers

    Time frame: Up to 24 hours after surgery

    Biomarkers from CSF and plasma samples will be quantified using Meso Scale Discovery multiplex kit (K15210D), for:

    CRP, Eotaxin, Eotaxin-3, FGF (basic), ICAM-1, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PlGF, SAA, TARC, Tie-2, TNF-α, TNF-β, VCAM-1, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1.

    The levels of these biomarkers will be compared between the group with depression/persistent pain, versus the group without depression/persistent pain.

Secondary outcomes

  1. CSF compared to plasma inflammatory cytokines/biomarkers

    Time frame: Preoperative samples

    Biomarkers will be quantified using Meso Scale Discovery multiplex kit (K15210D), for:

    CRP, Eotaxin, Eotaxin-3, FGF (basic), ICAM-1, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PlGF, SAA, TARC, Tie-2, TNF-α, TNF-β, VCAM-1, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1

    The CSF and plasma levels of these biomarkers will be compared within each group (group with depression/persistent pain, versus group without depression/persistent pain)

Sponsors and collaborators

Lead sponsor

Duke University

Other

Registry information

Official study title

The Role of Cerebrospinal Fluid and Serum Inflammatory Biomarkers in Predicting Perinatal Depression and Persistent Pain After Cesarean Delivery

Important dates

Study start
2020
Primary completion
2022
Study completion
2022
First posted
Feb 17, 2020
Registry last updated
Dec 20, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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