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

NCT ID: NCT04271072

Last Updated: 2023-12-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

81 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-02-01

Study Completion Date

2022-02-28

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Perinatal Depression Chronic Pain

Keywords

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Neuroinflammation Biomarker Cesarean delivery Cytokines Cerebrospinal fluid

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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)

No intervention

Intervention Type OTHER

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)

No intervention

Intervention Type OTHER

No intervention

Interventions

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No intervention

No intervention

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

40 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Duke University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mary Yurashevich

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

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Duke University Medical Center

Durham, North Carolina, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 28122130 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30557551 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23608136 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20015486 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29462012 (View on PubMed)

Yurashevich M, Cooter Wright M, Sims SC, Tan HS, Berger M, Ji RR, Habib AS. Inflammatory changes in the plasma and cerebrospinal fluid of patients with persistent pain and postpartum depression after elective Cesarean delivery: an exploratory prospective cohort study. Can J Anaesth. 2023 Dec;70(12):1917-1927. doi: 10.1007/s12630-023-02603-2. Epub 2023 Nov 6.

Reference Type DERIVED
PMID: 37932648 (View on PubMed)

Other Identifiers

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Pro00104111

Identifier Type: -

Identifier Source: org_study_id