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

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ClinicalTrials.gov Identifier: NCT04271072
Recruitment Status : Recruiting
First Posted : February 17, 2020
Last Update Posted : May 3, 2021
Sponsor:
Information provided by (Responsible Party):
Duke University

Brief Summary:

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.


Condition or disease Intervention/treatment
Perinatal Depression Chronic Pain Other: No intervention

Detailed Description:

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.

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.

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Study Type : Observational
Estimated Enrollment : 70 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Role of Cerebrospinal Fluid and Serum Inflammatory Biomarkers in Predicting Perinatal Depression and Persistent Pain After Cesarean Delivery
Actual Study Start Date : February 1, 2020
Estimated Primary Completion Date : January 1, 2022
Estimated Study Completion Date : July 1, 2022

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Study

Parturients that underwent cesarean delivery and is POSITIVE for the composite outcome of either:

  • perinatal depression (Edinburgh postnatal depression scale >=10 during pregnancy or within 3 months after delivery), and/or
  • persistent pain (pain score >=3 at pelvic or lower abdominal areas at 3 months after delivery)
Other: No intervention
No intervention

Control

Parturients that underwent cesarean delivery and is NEGATIVE for the composite outcome of both:

  • perinatal depression (Edinburgh postnatal depression scale >=10 during pregnancy or within 3 months after delivery), AND
  • persistent pain (pain score >=3 at pelvic or lower abdominal areas at 3 months after delivery)
Other: No intervention
No intervention




Primary Outcome Measures :
  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 Outcome Measures :
  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)



Biospecimen Retention:   Samples With DNA
Blood and CSF samples


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Only pregnant parturients are eligible
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Tertiary care hospital, specialist obstetric unit
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04271072


Contacts
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Contact: Mary Yurashevich 919-684-8111 mary.yurashevich@duke.edu

Locations
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United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Mary Yurashevich    919-684-8111    mary.yurashevich@duke.edu   
Sponsors and Collaborators
Duke University
Investigators
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Principal Investigator: Mary Yurashevich Duke University
Publications:
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Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT04271072    
Other Study ID Numbers: Pro00104111
First Posted: February 17, 2020    Key Record Dates
Last Update Posted: May 3, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Duke University:
Neuroinflammation
Biomarker
Cesarean delivery
Cytokines
Cerebrospinal fluid
Additional relevant MeSH terms:
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Asphyxia Neonatorum
Chronic Pain
Depression
Behavioral Symptoms
Pain
Neurologic Manifestations
Infant, Newborn, Diseases