- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04271072
CSF/Serum Biomarkers in Predicting PND/Persistent Pain After Cesarean
The Role of Cerebrospinal Fluid and Serum Inflammatory Biomarkers in Predicting Perinatal Depression and Persistent Pain After Cesarean Delivery
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
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.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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North Carolina
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Durham, North Carolina, United States, 27710
- Duke University Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
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
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Study
Parturients that underwent cesarean delivery and is POSITIVE for the composite outcome of either:
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No intervention
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Control
Parturients that underwent cesarean delivery and is NEGATIVE for the composite outcome of both:
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No intervention
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Perinatal depression
Time Frame: Up to 3 months after delivery
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Edinburgh postnatal depression scale >=10 (minimum 0, maximum 30, increasing score indicates higher likelihood of depression)
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Up to 3 months after delivery
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Persistent pain: Pain score
Time Frame: Up to 3 months after delivery
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Pain score >=3 at pelvic or lower abdominal areas (minimum 0, maximum 10, higher score indicates greater pain)
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Up to 3 months after delivery
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Inflammatory cytokines/biomarkers
Time Frame: Up to 24 hours after surgery
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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. |
Up to 24 hours after surgery
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
CSF compared to plasma inflammatory cytokines/biomarkers
Time Frame: Preoperative samples
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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) |
Preoperative samples
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Mary Yurashevich, Duke University
Publications and helpful links
General Publications
- Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctot KL. A meta-analysis of cytokines in major depression. Biol Psychiatry. 2010 Mar 1;67(5):446-57. doi: 10.1016/j.biopsych.2009.09.033. Epub 2009 Dec 16.
- Osborne LM, Monk C. Perinatal depression--the fourth inflammatory morbidity of pregnancy?: Theory and literature review. Psychoneuroendocrinology. 2013 Oct;38(10):1929-52. doi: 10.1016/j.psyneuen.2013.03.019. Epub 2013 Apr 20.
- Kohler CA, Freitas TH, Maes M, de Andrade NQ, Liu CS, Fernandes BS, Stubbs B, Solmi M, Veronese N, Herrmann N, Raison CL, Miller BJ, Lanctot KL, Carvalho AF. Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies. Acta Psychiatr Scand. 2017 May;135(5):373-387. doi: 10.1111/acps.12698. Epub 2017 Jan 25.
- Miller ES, Sakowicz A, Roy A, Yang A, Sullivan JT, Grobman WA, Wisner KL. Plasma and cerebrospinal fluid inflammatory cytokines in perinatal depression. Am J Obstet Gynecol. 2019 Mar;220(3):271.e1-271.e10. doi: 10.1016/j.ajog.2018.12.015. Epub 2018 Dec 14.
- Ji RR, Nackley A, Huh Y, Terrando N, Maixner W. Neuroinflammation and Central Sensitization in Chronic and Widespread Pain. Anesthesiology. 2018 Aug;129(2):343-366. doi: 10.1097/ALN.0000000000002130.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- Pro00104111
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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